NeuroImage

Overlapping activity in anterior insula during interoception and emotional experience.

Publication Date: 2012 May 12 PMID: 22587900
Authors: Zaki, J. - Davis, J. I. - Ochsner, K. N.
Journal: Neuroimage

Classic theories of emotion posit that awareness of one's internal bodily states (interoception) is a key component of emotional experience. This view has been indirectly supported by data demonstrating similar patterns of brain activity-most importantly, in the anterior insula-across both interoception and emotion elicitation. However, no study has directly compared these two phenomena within participants, leaving it unclear whether interoception and emotional experience truly share the same functional neural architecture. The current study addressed this gap in knowledge by examining the neural convergence of these two phenomena within the same population. In one task, participants monitored their own heartbeat; in another task they watched emotional video clips and rated their own emotional responses to the videos. Consistent with prior research, heartbeat monitoring engaged a circumscribed area spanning insular cortex and adjacent inferior frontal operculum. Critically, this interoception-related cluster also was engaged when participants rated their own emotion, and activity here correlated with the trial-by-trial intensity of participants' emotional experience. These findings held across both group-level and individual participant-level approaches to localizing interoceptive cortex. Together, these data further clarify the functional role of the anterior insula and provide novel insights about the connection between bodily awareness and emotion.

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Arteries dominate volume changes during brief functional hyperemia: Evidence from mathematical modelling.

Publication Date: 2012 May 12 PMID: 22587899
Authors: Barrett, M. J. - Tawhai, M. H. - Suresh, V.
Journal: Neuroimage

Variations in local neural activity are accompanied by rapid, focal changes in cerebral blood flow and volume. While a range of observations have shown that dilation occurs in cerebral arteries, there is conflicting evidence about the significanceof volume changes in post-arteriole vessels. Here, we reconcile the competing observations using a new mathematical model of the hemodynamic response. First, we followed a 'top down' approach, without constraining the model, but using experimental observations at progressively more detailed scales to ensure physiological behaviour. Then, we blocked dilation of post-arteriole vessels, and predicted observations at progressively more aggregated scales (a 'bottom up' approach). Predictions of blood flow, volume, velocity, and vessel diameter changes were consistent with experimental observations. Interestingly, the model predicted small, slow increases in capillary and venous diameter in agreement with recent in vivo data. Blocking dilation in these vessels led to erroneous volume predictions. The results are further evidence that arteries make up the majority of blood volume increases during brief functional activation. However, dilation of capillaries and veins appears to be increasingly significant during extended stimulation. These are important considerations when interpreting results from different neurovascular imaging modalities.

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Neuroanatomical correlates of visual car expertise.

Publication Date: 2012 May 12 PMID: 22587898
Authors: Gilaie-Dotan, S. - Harel, A. - Bentin, S. - Kanai, R. - Rees, G.
Journal: Neuroimage

Expertise in non-visual domains such as musical performance is associated with differences in gray matter volume of particular regions of the human brain. Whether this is also the case for expertise in visual object recognition is unknown. Here we tested whether individual variability in the ability to recognize car models, from novice performance to high level of expertise, is associated with specific structural changes in gray matter volume. We found that inter-individual variability in expertise with cars was significantly and selectively correlated with gray matter volume in prefrontal cortex. Inter-individual differences in the recognition of airplanes, that none of the participants had expertise with, were correlated with structural variability of regions bordering the visual cortex. These results highlight the role of prefrontal regions outside the visual cortex in accessing and processing visual knowledge about objects from the domain of expertise and suggest that expertise in visual object recognition may entail structural changes in regions associated with semantic knowledge.

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5-HTTLPR status predictive of neocortical 5-HT(4) binding assessed with [(11)C]SB207145 PET in humans.

Publication Date: 2012 May 11 PMID: 22584237
Authors: Fisher, P. M. - Holst, K. K. - Mc Mahon, B. - Haahr, M. H. - Madsen, K. - Gillings, N. - Baare, W. F. - Jensen, P. S. - Knudsen, G. M.
Journal: Neuroimage

Serotonin (5-HT) is a neuromodulator affecting myriad aspects of personality and behavior and has been implicated in the pathophysiology of affective disorders including depression and anxiety. The 5-HTTLPR is a common genetic polymorphism within the promoter region of the gene coding for the serotonin transporter such that the S allele is associated with reduced transcriptional efficacy compared to the L allele, potentially contributing to increased serotonin levels. In humans, this genetic variant has been linked to inter-individual variability in risk for affective disorders, related aspects of personality and brain function including response to threat. However, its effects on aspects of serotonin signaling in humans are not fully understood. Studies in animals suggest the 5-HT 4 receptor (5-HT(4)) shows a monotonic inverse association with long-term changes in serotonin levels indicating it may be a useful measure for identifying differences in serotonergic neurotransmission. In 47 healthy adults we evaluated the association between 5-HTTLPR status and in vivo 5-HT(4) receptor binding assessed with [(11)C]SB207145 positron emission tomography (PET). We observed a significant association within the neocortex where [(11)C]SB207145 binding was 9% lower in S carriers compared to LL homozygotes. We did not find evidence for an effect of season or a season-by-5-HTTLPR interaction effect on regional [(11)C]SB207145 binding. Our findings are consistent with a model wherein the 5-HTTLPR S allele is associated with relatively increased serotonin levels. These findings provide novel evidence supporting an effect of 5-HTTLPR status on serotonergic neurotransmission in adult humans. There were no indications of seasonal effects on serotonergic neurotransmission.

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Touch and personality: Extraversion predicts somatosensory brain response.

Publication Date: 2012 May 11 PMID: 22584236
Authors: Schaefer, M. - Heinze, H. J. - Rotte, M.
Journal: Neuroimage

The Five-Factor-Model describes human personality in five core dimensions (extraversion, neuroticism, agreeableness, conscientiousness, and openness). These factors are supposed to have different neural substrates. For example, it has been suggested that behavioral differences between introverts and extraverts can be explained by the fact that introverts exhibit an inherent drive to compensate for overactive cortical activity in reticulo-thalamo-cortical pathways. The current study examined if responses in somatosensory cortices due to tactile stimulation are affected by personality traits. Based on previous studies and theoretical models we hypothesized a relationship of extraversion with somatosensory responses in primary somatosensory cortex (SI). In order to test this hypothesis we applied nonpainful tactile stimulation on the fingers of both hands of 23 healthy young participants (mean 25 years, standard deviation+/-2.8 years). Personality traits were assessed according to the Five-Factor-Model (NEO-FFI). Neuromagnetic source imaging revealed that the cortical activity (dipole strengths) for sources in SI were closely associated with the personality trait extraversion. Thus, the less extraverted the participants were, the higher was the cortical activity in SI. This relationship was in particular valid for the right hemisphere. We conclude that personality seem to depend on primary cortex activity. Furthermore, our results provide further evidence for an inter-hemispheric asymmetry of the social brain.

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Single-trial EEG-fMRI coupling of the emotional auditory early posterior negativity.

Publication Date: 2012 May 11 PMID: 22584235
Authors: Jaspers-Fayer, F. - Ertl, M. - Leicht, G. - Leupelt, A. - Mulert, C.
Journal: Neuroimage

Event-related potential (ERP) studies in the visual domain often report an emotion-evoked early posterior negativity (EPN). Studies in the auditory domain have recently shown a similar component. Little source localization has been done on the visual EPN, and no source localization has been done on the auditory EPN. The aim of the current study was to identify the neural generators of the auditory EPN using EEG-fMRI single-trial coupling. Data were recorded from 19 subjects who completed three auditory choice reaction tasks: (1) a control task using neutral tones; (2) a prosodic emotion task involving the categorization of syllables; and (3) a semantic emotion task involving the categorization of words. The waveforms of the emotion tasks diverged from the neutral task over parietal scalp during a very early time window (132 - 156ms) and later during a more traditional EPN time window (252 - 392ms). In the EEG-fMRI analyses, the variance of the voltage in the earlier time window was correlated with activity in the medial prefrontal cortex, but only in the words task. In the EEG-fMRI analyses of the traditional EPN time window both emotional tasks covaried with activity in the left superior parietal lobule. Our results support previous parietal cortex source localization findings for the visual EPN, and suggest enhanced selective attention to emotional stimuli during the EPN time window.

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Brain tissue water comes in two pools: Evidence from diffusion and R2' measurements with USPIOs in non human primates.

Publication Date: 2012 May 11 PMID: 22584234
Authors: Le Bihan, D. - Joly, O. - Aso, T. - Uhrig, L. - Poupon, C. - Tani, N. - Iwamuro, H. - Urayama, S. I. - Jarraya, B.
Journal: Neuroimage

Diffusion-weighted MRI of non-human primates revealed that USPIO Bulk Magnetic Susceptibility (BMS) T2' effects of Ultrasmall Superparamagnetic Particles with Iron Oxide (USPIO) in the brain cannot be explained by a single compartment model, as diffusion and T2' effects appear coupled: Apparent Diffusion Coefficient (ADC) values depend on USPIO concentration and relaxivity effects of USPIO decrease with the b value. On the other hand, USPIO and diffusion effects could be well uncoupled using a model consisting in a fast and a slow diffusion pool with different relaxivities. Diffusion-weighting acts as a filter which emphasizes the contribution of the slow pool when increasing b values (apparent decrease in ADC and R2'). Those results have implications for human studies using BMS contrast agents, as well as BOLD and diffusion fMRI.

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Structural and Functional Neuroimaging Phenotypes in Dysbindin Mutant Mice.

Publication Date: 2012 May 11 PMID: 22584233
Authors: Lutkenhoff, E. - Karlsgodt, K. H. - Gutman, B. - Stein, J. L. - Thompson, P. M. - Cannon, T. D. - Jentsch, J. D.
Journal: Neuroimage

Schizophrenia is a highly heritable psychiatric disorder that is associated with a number of structural and functional neurophenotypes. DTNBP1, the gene encoding dysbindin-1, is a promising candidate gene for schizophrenia. Use of a mouse model carrying a large genomic deletion exclusively within the dysbindin gene permits a direct investigation of the gene in isolation. Here, we use manganese-enhanced magnetic resonance imaging (MEMRI) to explore the regional alterations in brain structure and function caused by loss of the gene encoding dysbindin-1. We report novel findings that uniquely inform our understanding of the relationship of dysbindin-1 to known schizophrenia phenotypes. First, in mutant mice, analysis of the rate of manganese uptake into the brain over a 24-hour period, putatively indexing basal cellular activity, revealed differences in dopamine rich brain regions, as well as in CA1 and dentate subregions of the hippocampus formation. Finally, novel tensor-based morphometry techniques were applied to the mouse MRI data, providing evidence for structural volume deficits in cortical regions, subiculum and dentate gyrus, and the striatum of dysbindin mutant mice. The affected cortical regions were primarily localized to the sensory cortices in particular the auditory cortex. This work represents the first application of manganese-enhanced small animal imaging to a mouse model of schizophrenia endophenotypes, and a novel combination of functional and structural measures. It revealed both hypothesized and novel structural and functional neural alterations related to dysbindin-1.

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It's All About You: An ERP Study of Emotion and Self-Relevance in Discourse.

Publication Date: 2012 May 11 PMID: 22584232
Authors: Fields, E. C. - Kuperberg, G. R.
Journal: Neuroimage

Accurately communicating self-relevant and emotional information is a vital function of language, but we have little idea about how these factors impact normal discourse comprehension. In an event-related potential (ERP) study, we fully crossed self-relevance and emotion in a discourse context. Two-sentence social vignettes were presented either in the third or the second person (previous work has shown that this influences the perspective from which mental models are built). ERPs were time-locked to a critical word toward the end of the second sentence which was pleasant, neutral, or unpleasant (e.g., A man knocks on Sandra's/your hotel room door. She/You see(s) that he has agift/tray/gunin his hand.). We saw modulation of early components (P1, N1, and P2) by self-relevance, suggesting that a self-relevant context can lead to top-down attentional effects during early stages of visual processing. Unpleasant words evoked a larger late positivity than pleasant words, which evoked a larger positivity than neutral words, indicating that, regardless of self-relevance, emotional words are assessed as motivationally significant, triggering additional or deeper processing at post-lexical stages. Finally, self-relevance and emotion interacted on the late positivity: a larger late positivity was evoked by neutral words in self-relevant, but not in non-self-relevant, contexts. This may reflect prolonged attempts to disambiguate the emotional valence of ambiguous stimuli that are relevant to the self. More broadly, our findings suggest that the assessment of emotion and self-relevance are not independent, but rather that they interactively influence one another during word-by-word language comprehension.

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Cortical activation during executed, imagined, observed, and passive wrist movements in healthy volunteers and stroke patients.

Publication Date: 2012 May 11 PMID: 22584231
Authors: Szameitat, A. J. - Shen, S. - Conforto, A. - Sterr, A.
Journal: Neuroimage

Motor imagery, passive movement, and movement observation have been suggested to activate the sensorimotor system without overt movement. The present study investigated these three covert movement modes together with overt movement in a within-subject design to allow for a fine-grained comparison of their abilities in activating the sensorimotor system, i.e. premotor, primary motor, and somatosensory cortices. For this, 21 healthy volunteers underwent functional magnetic resonance imaging (fMRI). In addition we explored the abilities of the different covert movement modes in activating the sensorimotor system in a pilot study of 5 stroke patients suffering from chronic severe hemiparesis. Results demonstrated that while all covert movement modes activated sensorimotor areas, there were profound differences between modes and between healthy volunteers and patients. In healthy volunteers, the pattern of neural activation in overt execution was best resembled by passive movement, followed by motor imagery, and lastly by movement observation. In patients, attempted overt execution was best resembled by motor imagery, followed by passive movement, and lastly by movement observation. Our results indicate that for severely hemiparetic stroke patients motor imagery may be the preferred way to activate the sensorimotor system without overt behavior. In addition, the clear differences between the covert movement modes point to the need for within-subject comparisons.

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Contrast-Enhanced Functional Blood Volume Imaging (CE-fBVI): Enhanced Sensitivity for Brain Activation in Humans using the Ultrasmall Superparamagnetic Iron Oxide Agent Ferumoxytol.

Publication Date: 2012 May 11 PMID: 22584230
Authors: Qiu, D. - Zaharchuk, G. - Christen, T. - Ni, W. W. - Moseley, M. E.
Journal: Neuroimage

Functional MRI (fMRI) brain studies performed in the presence of a steady-state or "blood pool" contrast agent yields activation maps that are weighted for cerebral blood volume (CBV). Previous animal experiments suggest significant contrast-to-noise (CNR) improvements, but these studies have not yet been performed in humans due to the lack of availability of a suitable agent. Here we report the use of the USPIO ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA) for functional brain activation in humans, termed contrast enhanced functional Blood Volume Imaging (CE-fBVI). Four subjects were scanned during a unilateral finger tapping task with standard blood-oxygen level dependent (BOLD) imaging before contrast and CE-fBVI after contrast injection. The CE-fBVI response showed both a fast (5.8+/-1.3sec) and a slow (75.3+/-27.5sec) component of CBV response to stimuli. A significant CNR gain of approximately 2-3 was found for CE-fBVI compared to BOLD fMRI. Interestingly, less susceptibility-related signal dropouts were observed in the inferior frontal and temporal lobes with CE-fBVI. The combination of higher CNR and better spatial specificity, enabled by CE-fBVI using blood pool USPIO contrast agent opens the door to higher resolution brain mapping.

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Left prefrontal cortex activation during sentence comprehension covaries with grammatical knowledge in children.

Publication Date: 2012 May 11 PMID: 22584229
Authors: Knoll, L. J. - Obleser, J. - Schipke, C. S. - Friederici, A. D. - Brauer, J.
Journal: Neuroimage

Children's language skills develop rapidly with increasing age, and several studies indicate that they use language- and age-specific strategies to understand complex sentences. In the present experiment, functional magnetic resonance imaging (fMRI) and behavioral measures were used to investigate the acquisition of case-marking cues for sentence interpretation in the developing brain of German preschool children with a mean age of 6years. Short sentences were presented auditorily, consisting of a transitive verb and two case-marked arguments with canonical subject-initial or non canonical object-initial word-order. Overall group results revealed mainly left hemispheric activation in the perisylvian cortex with increased activation in the inferior parietal cortex (IPC), and the anterior cingulate cortex (ACC) for object-initial compared to subject-initial sentences. However, single subject analysis suggested two distinct activation patterns within the group which allowed a classification into two subgroups. One subgroup showed the predicted activation increase in the left inferior frontal gyrus (IFG) for the more difficult object-initial compared to subject-initial sentences, while the other group showed the reverse effect. This activation in the left IFG can be taken to reflect the degree to which adult-like sentence processing strategies, necessary to integrate case-marking information, are applied. Additional behavioral data on language development tests show that these two subgroups differ in their grammatical knowledge. Together with these behavioral findings, the results indicate that the use of a particular processing strategy is not dependent on age as such, but rather on the child's individual grammatical knowledge and the ability to use specific language cues for successful sentence comprehension.

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Illusory movements prevent cortical disruption caused by immobilization.

Publication Date: 2012 May 11 PMID: 22584228
Authors: Roll, R. - Kavounoudias, A. - Albert, F. - Legre, R. - Gay, A. - Fabre, B. - Roll, J. P.
Journal: Neuroimage

Enforced limb disuse strongly disrupts the cortical networks that are involved in sensorimotor activities. This disruption causes a cortical reorganization that may be functionally maladaptive. In this study, we used functional magnetic resonance imaging (fMRI) to investigate whether it is possible to prevent this reorganization by compensating for the lack of actual kinesthetic perception with illusory movements induced by "neuromimetic" proprio-tactile feedback that is artificially delivered during immobilization. Sixteen healthy volunteers were equipped for five days with full-hand ortheses that prevented them from performing finger and hand movements but allowed for kinesthetic and tactile sensations. Eight participants received a twice-daily proprio-tactile treatment consisting of the perception of kinesthetic sensations resembling those felt during actual movements generated by miniature vibrators set in the ortheses at the finger and wrist levels. Eight untreated participants received no stimulation. The effects of hand immobilization and treatment were assessed by fMRI during a calibrated voluntary hand movement task and hand tactile stimulation before cast placement and immediately after cast removal. We found that the sensorimotor network was preserved in subjects who underwent this treatment during hand immobilization, while the sensorimotor network of untreated subjects was significantly altered. These findings suggest that sensory feedback and associated movement perception may counteract disuse-induced cortical plastic changes through recruitment of a large part of the cortical network used for actual performed movement. The possibility of guiding cortical plasticity with proprioceptive augmented feedback is potentially relevant for rehabilitation efforts.

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Influences of Skull Segmentation Inaccuracies on EEG Source Analysis.

Publication Date: 2012 May 11 PMID: 22584227
Authors: Lanfer, B. - Scherg, M. - Dannhauer, M. - Knosche, T. R. - Burger, M. - Wolters, C. H.
Journal: Neuroimage

The low-conducting human skull is known to have an especially large influence on electroencephalography (EEG) source analysis. Because of difficulties segmenting the complex skull geometry out of magnetic resonance images, volume conductor models for EEG source analysis might contain inaccuracies and simplifications regarding the geometry of the skull. The computer simulation study presented here investigated the influences of a variety of skull geometry deficiencies on EEG forward simulations and source reconstruction from EEG data. Reference EEG data was simulated in a detailed and anatomically plausible reference model. Test models were derived from the reference model representing a variety of skull geometry inaccuracies and simplifications. These included erroneous skull holes, local errors in skull thickness, modeling cavities as bone, downward extension of the model and simplifying the inferior skull or the inferior skull and scalp as layers of constant thickness. The reference EEG data was compared to forward simulations in the test models, and source reconstruction in the test models was performed on the simulated reference data. The finite element method with high-resolution meshes was employed for all forward simulations. It was found that large skull geometry inaccuracies close to the source space, for example, when cutting the model directly below the skull, led to errors of 20mm and more for extended source space regions. Local defects, for example, erroneous skull holes, caused non-negligible errors only in the vicinity of the defect. The study design allowed a comparison of influence size, and guidelines for modeling the skull geometry were concluded.

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Age related differences in the neural substrates of motor sequence learning after interleaved and repetitive practice.

Publication Date: 2012 May 11 PMID: 22584226
Authors: Lin, C. H. - Chiang, M. C. - Wu, A. D. - Iacoboni, M. - Udompholkul, P. - Yazdanshenas, O. - Knowlton, B. J.
Journal: Neuroimage

Practice of tasks in an interleaved order generally induces superior retention compared to practicing in a repetitive order. Younger and older adults practiced serial reaction time tasks that were arranged in a repeated or an interleaved order on 2 successive days. Retention was tested on Day 5. For both groups, reaction times in the interleaved condition were slower than the repetitive condition during practice, but the reverse was true during retention on Day 5. After interleaved practice, changes in M1 excitability measured by paired-pulse TMS were greater than after repetitive practice, and this effect was more pronounced in older adults. Moreover, the increased M1 excitability correlated with the benefit of interleaved practice. BOLD signal was also increased for interleaved compared to repetitive practice in both groups. However, the pattern of correlations between increased BOLD during practice and subsequent benefit of the interleaved condition differed by group. In younger adults, dorsolateral-prefrontal activity during practice was related to this benefit, while in older adults, activation in sensorimotor regions and rostral prefrontal cortex during practice correlated with the benefit of interleaving on retention. Older adults may engage compensatory mechanisms during interleaved practice such as increasing sensorimotor recruitment which in turn benefits learning.

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Familiarity modulates the functional relationship between theory of mind and autobiographical memory.

Publication Date: 2012 May 11 PMID: 22584225
Authors: Rabin, J. S. - Rosenbaum, R. S.
Journal: Neuroimage

Qualitative and quantitative reviews of the neuroimaging literature show that overlapping brain regions support theory of mind (ToM) and autobiographical memory (AM). This overlap has been taken to suggest that individuals draw on past personal experiences to infer others' mental states, but work with amnesic people shows that ToM does not always depend on AM. One variable that may determine the extent to which one relies on AM when inferring another's thoughts and feelings during ToM is whether that individual is personally known. To test this possibility, participants were scanned with fMRI as they remembered past experiences in response to personal photos ('AM' condition) and imagined others' experiences in response to photos of personally familiar ('pToM' condition) and unfamiliar ('ToM' condition) others. Spatiotemporal Partial Least Squares was used to identify the spatial and temporal characteristics of neural activation patterns associated with AM, pToM, and ToM. We found that the brain regions supporting pToM more closely resembled those supporting AM relative to ToM involving unfamiliar others, with the greatest degree of overlap within midline regions. A complementary finding was the observation of striking differences between pToM and ToM such that midline regions associated with AM predominated during pToM, whereas more lateral regions associated with social semantic memory predominated during ToM. Overall, this study demonstrates that ToM involves a dynamic interplay between AM and social semantic memory that is biased towards AM when a personally familiar other is the subject of the mental state inference.

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A review and synthesis of the first 20 years of PET and fMRI studies of heard speech, spoken language and reading.

Publication Date: 2012 May 11 PMID: 22584224
Authors: Price, C. J.
Journal: Neuroimage

The anatomy of language has been investigated with PET or fMRI for more than 20 years. Here I attempt to provide an overview of the brain areas associated with heard speech (Section 1), speech production (Section 2) and reading (Section 3). The conclusions of many hundreds of studies were considered, grouped according to the type of processing, and reported in the order that they were published. Many findings have been replicated time and time again leading to some consistent and undisputable conclusions. These are summarised in an anatomical model that indicates the location of the language areas and the most consistent functions that have been assigned to them. The implications for cognitive models of language processing are also considered. In particular, a distinction can be made between processes that are localised to specific structures (e.g. sensory and motor processing) and processes where specialisation arises in the distributed pattern of activation over many different areas that each participate in multiple functions. For example, phonological processing of heard speech is supported by the functional integration of auditory processing and articulation; and orthographic processing is supported by the functional integration of visual processing, articulation and semantics. Future studies will undoubtedly be able to improve the spatial precision with which functional regions can be dissociated but the greatest challenge will be to understand how different brain regions interact with one another in their attempts to comprehend and produce language.

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Overcoming residual interference in mental set switching: Neural correlates and developmental trajectory.

Publication Date: 2012 May 11 PMID: 22584223
Authors: Witt, S. T. - Stevens, M. C.
Journal: Neuroimage

Mental set switching is a key facet of executive control measured behaviorally through reaction time or accuracy (i.e., 'switch costs') when shifting among task types. One of several experimentally-dissociable influences on switch costs is 'task set inertia', conceptualized as the residual interference conferred when a previous stimulus-response tendency interferes with subsequent stimulus processing on a new task. Task set inertia is thought to represent the passive decay of the previous stimulus-response set from working memory, and its effects decrease with increased interstimulus interval. Closely spaced trials confer high task set inertia, while sparsely spaced trials confer low task set inertia. This functional magnetic resonance imaging (fMRI) study characterized, for the first time, two opposing brain systems engaged to resolve task set inertia: 1) a frontoparietal 'cortical control' network for overcoming high task set inertia interference and 2) a subcortical-motor network more active during trials with low task set inertia. These networks were distinct from brain regions showing general switching effects (i.e., switch>non-switch) and from other previously-characterized interference effects. Moreover, there were ongoing maturational effects throughout adolescence for the brain regions engaged to overcome high task set inertia not seen for generalized switching effects. These novel findings represent a new avenue of exploration of cognitive set switching neural function.

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A Time-Varying Source Connectivity Approach to Reveal Human Somatosensory Information Processing.

Publication Date: 2012 May 10 PMID: 22580382
Authors: Hu, L. - Zhang, Z. G. - Hu, Y.
Journal: Neuroimage

Exploration of neural sources and their effective connectivity based on transient changes in electrophysiological activities to external stimuli is important for understanding brain mechanisms of sensory information processing. However, such cortical mechanisms have not yet been well characterized in electrophysiological studies since (1) it is difficult to estimate the stimulus-activated neural sources and their activities and (2) it is difficult to identify transient effective connectivity between neural sources in the order of millisecond. To address these issues, we developed a time-varying source connectivity approach to effectively capture fast-changing information flows between neural sources from high-density Electroencephalography (EEG) recordings. This time-varying source connectivity approach was applied to somatosensory evoked potentials (SEPs), which were elicited by electrical stimulation of right hand and recorded using 64 channels from 16 subjects, to reveal human somatosensory information processing. First, SEP sources and their activities were estimated, both at single-subject and group level, using equivalent current dipolar source modeling. Then, the functional integration among SEP sources was explored using a Kalman smoother based time-varying effective connectivity inference method. The results showed that SEPs were mainly generated from the contralateral primary somatosensory cortex (SI), bilateral secondary somatosensory cortex (SII), and cingulate cortex (CC). Importantly, we observed a serial processing of somatosensory information in human somatosensory cortices (from SI to SII) at earlier latencies (<150ms) and a reciprocal processing between SII and CC at later latencies (>200ms).

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Real-time imaging of cortical areas involved in the generation of increases in skin sympathetic nerve activity when viewing emotionally charged images.

Publication Date: 2012 May 2 PMID: 22580171
Authors: Henderson, L. - Stathis, A. - James, C. - Brown, R. - McDonald, S. - Macefield, V. G.
Journal: Neuroimage

The sympathetic innervation of the skin not only primarily subserves thermoregulation, but has also been commandeered as a means of emotional expression. While the majority of brain imaging studies of emotion have utilised the galvanic skin response as a means of inferring changes in skin sympathetic nerve activity (SSNA), spontaneous fluctuations in the galvanic skin response bear little relation to spontaneous fluctuations in SSNA. To improve our understanding of the central neural processes involved in the generation of autonomic emotional markers, we recorded SSNA concurrently with brain functional magnetic resonance imaging in 13 subjects. Emotional changes were evoked by presentation of positively-charged (erotica) or negatively-charged (mutilation) images from the International Affective Picture System. Positive and negative emotionally-charged images evoked significant increases in total SSNA and signal intensity in the orbital, dorsolateral and ventromedial prefrontal cortices, amygdala, nucleus accumbens and anterior insula. Increases in signal intensity during increases in SSNA occurred in a number of brain regions, including the central and lateral amygdala, dorsolateral pons, thalamus, nucleus accumbens, and cerebellar cortex. Signal intensity decreases during SSNA increases occurred in the left orbitofrontal, frontal and right precuneus cortices. These data reveal for the first time, cortical and subcortical sites involved in generating SSNA changes during emotions.

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Combining MRI and CSF measures for classification of Alzheimer's disease and prediction of mild cognitive impairment conversion.

Publication Date: 2012 May 3 PMID: 22580170
Authors: Westman, E. - Muehlboeck, J. S. - Simmons, A.
Journal: Neuroimage

The suggested revision of the NINCDS-ADRDA criterion for the diagnosis of Alzheimer's disease (AD) includes at least one abnormal biomarker among magnetic resonance imaging (MRI), positron emission tomography (PET) and cerebrospinal fluid (CSF). We aimed to investigate if the combination of baseline MRI and CSF could enhance the classification of AD compared to using either alone and predict mild cognitive impairment (MCI) conversion at multiple future time points. 369 subjects from the Alzheimer's disease Neuroimaging Initiative (ADNI) were included in the study (AD=96, MCI=162 and CTL=111). Freesurfer was used to generate regional subcortical volumes and cortical thickness measures. A total of 60 variables were used for orthogonal partial least squares to latent structures (OPLS) multivariate analysis (57 MRI measures and 3 CSF measures: Abeta(42), t-tau and p-tau). Combining MRI and CSF gave the best results for distinguishing AD vs. CTL. We found an accuracy of 91.8% for the combined model at baseline compared to 81.6% for CSF measures and 87.0% for MRI measures alone. The combined model also gave the best accuracy when distinguishing between MCI vs. CTL (77.6%) at baseline. MCI subjects who converted to AD by 12 and 18month follow-up were accurately predicted at baseline using an AD vs. CTL model (82.9% and 86.4% respectively), with lower prediction accuracies for those MCI subjects converting by 24 and 36month follow up (75.4% and 68.0% respectively). The overall prediction accuracies for converters and non-converters ranged from 58.6 to 66.4% at different time points. Combining MRI and CSF measures in a multivariate model at baseline gave better accuracy for discriminating between AD and CTL, between MCI and CTL and for predicting future conversion from MCI to AD, than using either MRI or CSF separately.

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Evidence for neural encoding of Bayesian surprise in human somatosensation.

Publication Date: 2012 May 3 PMID: 22579866
Authors: Ostwald, D. - Spitzer, B. - Guggenmos, M. - Schmidt, T. T. - Kiebel, S. J. - Blankenburg, F.
Journal: Neuroimage

Accumulating empirical evidence suggests a role of Bayesian inference and learning for shaping neural responses in auditory and visual perception. However, its relevance for somatosensory processing is unclear. In the present study we test the hypothesis that cortical somatosensory processing exhibits dynamics that are consistent with Bayesian accounts of brain function. Specifically, we investigate the cortical encoding of Bayesian surprise, a recently proposed marker of Bayesian perceptual learning, using EEG data recorded from 15 subjects. Capitalizing on a somatosensory mismatch roving paradigm, we performed computational single-trial modeling of evoked somatosensory potentials for the entire peri-stimulus time period in source space. By means of Bayesian model selection, we find that, at 140ms post-stimulus onset, secondary somatosensory cortex represents Bayesian surprise rather than stimulus change, which is the conventional marker of EEG mismatch responses. In contrast, at 250ms, right inferior frontal cortex indexes stimulus change. Finally, at 360ms, our analyses indicate additional perceptual learning attributable to medial cingulate cortex. In summary, the present study provides novel evidence for anatomical-temporal/functional segregation in human somatosensory processing that is consistent with the Bayesian brain hypothesis.

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Stochastic dynamic causal modeling of fMRI data: Should we care about neural noise?

Publication Date: 2012 May 9 PMID: 22579726
Authors: Daunizeau, J. - Stephan, K. E. - Friston, K. J.
Journal: Neuroimage

Dynamic causal modeling (DCM) was introduced to study the effective connectivity among brain regions using neuroimaging data. Until recently, DCM relied on deterministic models of distributed neuronal responses to external perturbation (e.g., sensory stimulation or task demands). However, accounting for stochastic fluctuations in neuronal activity and their interaction with task-specific processes may be of particular importance for studying state-dependent interactions. Furthermore, allowing for random neuronal fluctuations may render DCM more robust to model misspecification and finesse problems with network identification. In this article, we examine stochastic dynamic causal models (sDCM) in relation to their deterministic counterparts (dDCM) and highlight questions that can only be addressed with sDCM. We also compare the network identification performance of deterministic and stochastic DCM, using Monte Carlo simulations and an empirical case study of absence epilepsy. For example, our results demonstrate that stochastic DCM can exploit the modeling of neural noise to discriminate between direct and mediated connections. We conclude with a discussion of the added value and limitations of sDCM, in relation to its deterministic homologue.

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Combining image-derived and venous input functions enables quantification of serotonin-1A receptors with [carbonyl-(11)C]WAY-100635 independent of arterial sampling.

Publication Date: 2012 May 2 PMID: 22579604
Authors: Hahn, A. - Nics, L. - Baldinger, P. - Ungersbock, J. - Dolliner, P. - Frey, R. - Birkfellner, W. - Mitterhauser, M. - Wadsak, W. - Karanikas, G. - Kasper, S. - Lanzenberger, R.
Journal: Neuroimage

Image-derived input functions (IDIFs) represent a promising technique for a simpler and less invasive quantification of PET studies as compared to arterial cannulation. However, a number of limitations complicate the routine use of IDIFs in clinical research protocols and the full substitution of manual arterial samples by venous ones has hardly been evaluated. This study aims for a direct validation of IDIFs and venous data for the quantification of serotonin-1A receptor binding (5-HT(1A)) with [carbonyl-(11)C]WAY-100635 before and after hormone treatment. METHODS: Fifteen PET measurements with arterial and venous blood sampling were obtained from 10 healthy women, 8 scans before and 7 after eight weeks of hormone replacement therapy. Image-derived input functions were derived automatically from cerebral blood vessels, corrected for partial volume effects and combined with venous manual samples from 10min onward (IDIF+VIF). Corrections for plasma/whole-blood ratio and metabolites were done separately with arterial and venous samples. 5-HT(1A) receptor quantification was achieved with arterial input functions (AIF) and IDIF+VIF using a two-tissue compartment model. RESULTS: Comparison between arterial and venous manual blood samples yielded excellent reproducibility. Variability (VAR) was less than 10% for whole-blood activity (p>0.4) and below 2% for plasma to whole-blood ratios (p>0.4). Variability was slightly higher for parent fractions (VARmax=24% at 5min, p<0.05 and VAR<13% after 20min, p>0.1) but still within previously reported values. IDIFs after partial volume correction had peak values comparable to AIFs (mean difference Delta=-7.6+/-16.9kBq/ml, p>0.1), whereas AIFs exhibited a delay (Delta=4+/-6.4s, p<0.05) and higher peak width (Delta=15.9+/-5.2s, p<0.001). Linear regression analysis showed strong agreement for 5-HT(1A) binding as obtained with AIF and IDIF+VIF at baseline (R(2)=0.95), after treatment (R(2)=0.93) and when pooling all scans (R(2)=0.93), with slopes and intercepts in the range of 0.97 to 1.07 and -0.05 to 0.16, respectively. In addition to the region of interest analysis, the approach yielded virtually identical results for voxel-wise quantification as compared to the AIF. CONCLUSIONS: Despite the fast metabolism of the radioligand, manual arterial blood samples can be substituted by venous ones for parent fractions and plasma to whole-blood ratios. Moreover, the combination of image-derived and venous input functions provides a reliable quantification of 5-HT(1A) receptors. This holds true for 5-HT(1A) binding estimates before and after treatment for both regions of interest-based and voxel-wise modeling. Taken together, the approach provides less invasive receptor quantification by full independence of arterial cannulation. This offers great potential for the routine use in clinical research protocols and encourages further investigation for other radioligands with different kinetics characteristics.

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NeuroImage Anniversary Issue.

Publication Date: 2012 Jun PMID: 22578314
Authors: Toga, A. W. - Frackowiak, R. - Mazziotta, J. C.
Journal: Neuroimage

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Understanding less than nothing: Neural distance effects for negative numbers.

Publication Date: 2012 May 7 PMID: 22575794
Authors: Gullick, M. M. - Wolford, G. - Temple, E.
Journal: Neuroimage

Little work has examined how the mental number system accommodates counterintuitive quantities such as negative numbers, which seem to extend the left end of the mental number line and reverse the established relationship between digit magnitude and value; even less research has been conducted on the neural systems supporting negative number understanding. This study aimed to determine whether adult behavioral and neural responses to negative number paired comparisons were similar to those expected for positive numbers. Mixed pairs (with one positive and one negative number) were also included. Negative number responses demonstrated an increased typical distance effect relative to that for positives, with decreasing response times and intraparietal sulcus activity for comparisons farther apart than those closer together. Negative pairs also showed more activity than positive comparisons across distances in the occipital lobe, inferior and superior parietal lobule, and bilateral caudate and putamen. Mixed pair effect direction varied based on polarity sensitivity, or whether attention to the negative sign was needed for accurate responses, indicating differences in processing strategy. Adults thus draw on brain areas important in numeric processing when dealing with negatives, but also recruit further areas and strategies to support the unique features of negative numbers. The increased distance effect seen may reflect a less mature understanding of negatives. This work expands our knowledge of the flexibility of the mental number system and its ability to represent difficult quantities.

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Neuroanatomical substrates involved in true and false memories for face.

Publication Date: 2012 Apr 28 PMID: 22575420
Authors: Iidaka, T. - Harada, T. - Kawaguchi, J. - Sadato, N.
Journal: Neuroimage

We often mistake an unknown person for a familiar person because of the similarities in facial features. This phenomenon, known as false memory, has been investigated mainly using words, pictures, and shapes. Previous neuroimaging studies on false memory have shown that both true and false memories trigger a similar activation in the medial temporal lobe, suggesting that it plays a common role in both. However, no study to date has investigated neural substrates of false memories for faces. In the present fMRI study, we applied a modified version of the standard false memory paradigm, using morphed pictures of faces, to induce false memory in an MRI environment. We found that activity in the amygdala and orbital cortices was associated with the degree of familiarity of items. In particular, false responses to "lure" items evoked a level of activity in the amygdala between that evoked for correct or incorrect responses to "true" items. This indicates a possible role of the amygdala in false memory. A specific region in the anterior cingulate cortex was involved in false recognition; the activity being correlated to reaction times for the response types. These results suggest that the amygdala is involved in determining the relevance of items; therefore, ambiguousness of lure items in terms of familiarity and novelty may be related to decreased activity in the amygdala. The anterior cingulate activity in false memory may be caused not only by increased effort and motor demand but also by higher mnemonic processing of lure items.

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Brain activations underlying different patterns of performance improvement during early motor skill learning.

Publication Date: 2012 May 6 PMID: 22569545
Authors: Lefebvre, S. - Dricot, L. - Gradkowski, W. - Laloux, P. - Vandermeeren, Y.
Journal: Neuroimage

BACKGROUND/INTRODUCTION: Motor learning plays a central role in daily life and in neurorehabilitation. Several forms of motor learning have been described, among which motor skill learning, i.e. reaching a superior level of performance (a skill) through a shift of the speed/accuracy trade-off. During the first stage of learning a visuomotor skill, we observed differential patterns of evolution of the speed/accuracy trade-off in normal subjects. Half of the subjects rapidly achieved successful motor skill learning with an early shift of the speed/accuracy trade-off leading to a superior level of performance ("shift" pattern). The other subjects attained only minimal global improvement due to a converse evolution of speed and accuracy (i.e. a respect of the speed/accuracy trade-off: "fit" pattern). Functional magnetic resonance imaging (fMRI) was used to explore the neural substrates underlying these differential patterns during the first stage of motor skill learning in normal subjects. METHODS: Twenty right-handed normal subjects performed an implicit visuomotor learning task with their non-dominant hand. The task ("circuit game") consisted in learning to navigate a pointer along a circuit as quickly and accurately as possible using a fMRI-compatible mouse. Velocity, accuracy, and performance indexes were used to characterise the motor learning pattern (shift/fit) and to perform fMRI correlation analysis in order to find the neural substrate associated with the shift and fit patterns during early motor skill learning. RESULTS: Nine subjects showed a fit pattern ("fitters"), and eleven, a shift pattern ("shifters"). fMRI analyses at whole group level (ANOVA) and at sub-group level demonstrated that the supplementary motor area (SMA) was more activated in "shifters" than in the "fitters" groups and that the BOLD activation within the SMA correlated significantly with the on-line shift of the speed/accuracy trade-off in the "shifters" group. CONCLUSION: Despite identical instructions and experimental conditions, during the first stage of motor skill learning normal subjects spontaneously adopted different patterns that can be differentiated based on distinct fMRI activation patterns. In this implicit visuomotor task, the SMA proper was the key area underlying the achievement of early successful motor skill learning, i.e. on-line shift of the speed/accuracy trade-off.

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Avoidance of harm and anxiety: A role for the nucleus accumbens.

Publication Date: 2012 May 5 PMID: 22569544
Authors: Levita, L. - Hoskin, R. - Champi, S.
Journal: Neuroimage

Active and passive avoidance behaviors involve either emitting or omitting a response to avoid potential harm. Both are key components in the etiology and maintenance of anxiety disorders, yet the neural circuitry that mediates avoidance is underexplored. Using functional magnetic resonance imaging greater hemodynamic activation of the nucleus accumbens was found during active avoidance, whereas greater deactivation of the nucleus accumbens was observed during passive avoidance. These findings extend the role of the NAcc from purely reward-based action-contingencies, to one that also involves either emitting or withholding a response to avoid harm. Critically, the degree of activation and deactivation of the NAcc during avoidance was associated with individual levels of anxiety, which supports the idea that the NAcc may play a key role in the etiology and maintenance of aberrant avoidance behaviors in disorders of anxiety.

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Electrophysiological and functional connectivity of the human supplementary motor area.

Publication Date: 2012 May 5 PMID: 22569543
Authors: Narayana, S. - Laird, A. R. - Tandon, N. - Franklin, C. - Lancaster, J. L. - Fox, P. T.
Journal: Neuroimage

Neuro-imaging methods for detecting functional and structural inter-regional connectivity are in a rapid phase of development. While reports of regional connectivity patterns based on individual methods are becoming common, studies comparing the results of two or more connectivity-mapping methods remain rare. In this study, we applied transcranial magnetic stimulation during PET imaging (TMS/PET), a stimulation-based method, and meta-analytic connectivity modeling (MACM), a task-based method to map the connectivity patterns of the supplementary motor area (SMA). Further, we drew upon the behavioral domain meta-data of the BrainMap(R) database to characterize the behavioral domain specificity of two maps. Both MACM and TMS/PET detected multi-synaptic connectivity patterns, with the MACM-detected connections being more extensive. Both MACM and TMS/PET detected connections belonging to multiple behavioral domains, including action, cognition and perception. Finally, we show that the two connectivity-mapping methods are complementary in that, the MACM informed on the functional nature of SMA connections, while TMS/PET identified brain areas electrophysiologically connected with the SMA. Thus, we demonstrate that integrating multimodal database and imaging techniques can derive comprehensive connectivity maps of brain areas.

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Changes in the brain intrinsic organization in both on-task state and post-task resting state.

Publication Date: 2012 May 5 PMID: 22569542
Authors: Wang, Z. - Liu, J. - Zhong, N. - Qin, Y. - Zhou, H. - Li, K.
Journal: Neuroimage

The dynamic and robust characteristics of intrinsic functional connectivity of coherent spontaneous activity are critical for the brain functional stability and flexibility. Studies have demonstrated modulation of intrinsic connectivity within local spatial patterns during or after task performance, such as the default mode network (DMN) and task-specific networks. Moreover, recent studies have compared the global spatial pattern in different tasks or over time. However, it is still unclear how the large-scale intrinsic connectivity varies during and after a task. To better understand this issue, we conducted a functional MRI experiment over three sequential periods: an active semantic-matching task period and two rest periods, before and after the task respectively (namely, on-task state and pre-/post-task resting states), to detect task-driven effect on the dynamic large-scale intrinsic organization in both on-task state and post-task resting state. Three hierarchical levels were investigated, including (a) the whole brain small-world topology, (b) the whole pairwise functional connectivity patterns both within the DMN and between the DMN and other regions (i.e., the global/full DMN topography), and (c) the DMN nodal graph properties. The major findings are: (1) The large-scale small-world configuration of brain functional organization is robust, regardless of the behavioral state changing, while it varies adaptively with significantly higher local efficiency and lower global efficiency during the on-task state (P<0.05, Monte-Carlo corrected); (2) The DMN may be essentially engaged during both task and post-task processes with adaptively varied spatial patterns and nodal graph properties. The present study provides further insights into the robustness and plasticity of the brain intrinsic organization over states, which may be the basis of memory and learning in the brain.

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Inferring task-related networks using independent component analysis in magnetoencephalography.

Publication Date: 2012 May 1 PMID: 22569064
Authors: Luckhoo, H. - Hale, J. R. - Stokes, M. G. - Nobre, A. C. - Morris, P. G. - Brookes, M. J. - Woolrich, M. W.
Journal: Neuroimage

A novel framework for analysing task-positive data in magnetoencephalography (MEG) is presented that can identify task-related networks. Techniques that combine beamforming, the Hilbert transform and temporal independent component analysis (ICA) have recently been applied to resting-state MEG data and have been shown to extract resting-state networks similar to those found in fMRI. Here we extend this approach in two ways. First, we systematically investigate optimisation of time-frequency windows for connectivity measurement. This is achieved by estimating the distribution of functional connectivity scores between nodes of known resting-state networks and contrasting it with a distribution of artefactual scores that are entirely due to spatial leakage caused by the inverse problem. We find that functional connectivity, both in the resting-state and during a cognitive task, is best estimated via correlations in the oscillatory envelope in the 8-20Hz frequency range, temporally down-sampled with windows of 1-4s. Second, we combine ICA with the general linear model (GLM) to incorporate knowledge of task structure into our connectivity analysis. The combination of ICA with the GLM helps overcome problems of these techniques when used independently: namely, the interpretation and separation of interesting independent components from those that represent noise in ICA and the correction for multiple comparisons when applying the GLM. We demonstrate the approach on a 2-back working memory task and show that this novel analysis framework is able to elucidate the functional networks involved in the task beyond that which is achieved using the GLM alone. We find evidence of localised task-related activity in the area of the hippocampus, which is difficult to detect reliably using standard methods. Task-positive ICA, coupled with the GLM, has the potential to be a powerful tool in the analysis of MEG data.

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Effects of beta-amyloid accumulation on neural function during encoding across the adult lifespan.

Publication Date: 2012 May 1 PMID: 22569063
Authors: Kennedy, K. M. - Rodrigue, K. M. - Devous, M. D. Sr - Hebrank, A. C. - Bischof, G. N. - Park, D. C.
Journal: Neuroimage

Limited functional imaging evidence suggests that increased beta-amyloid deposition is associated with alterations in brain function, even in healthy older adults. However, the majority of these findings report on resting-state activity or functional connectivity in adults over age 60. Much less is known about the impact of beta-amyloid on neural activations during cognitive task performance, or the impact of amyloid in young and middle-aged adults. The current study measured beta-amyloid burden from PET imaging using (18)Florbetapir, in a large continuous age sample of highly-screened, healthy adults (N=137; aged 30-89years). The same participants also underwent fMRI scanning, performing a memory encoding task. Using both beta-amyloid burden and age as continuous predictors of encoding activity, we report a dose-response relationship of beta-amyloid load to neural function, beyond the effects of age. Specifically, individuals with greater amyloid burden evidence less neural activation in bilateral dorsolateral prefrontal cortex, a region important for memory encoding, as well as reduced neural modulation in areas associated with default network activity: bilateral superior/medial frontal and lateral temporal cortex. Importantly, this reduction of both activation and suppression as a function of amyloid load was found across the lifespan, even in young- and middle-aged individuals. Moreover, this frontal and temporal amyloid-reduced activation/suppression was associated with poorer processing speed, verbal fluency, and fluid reasoning in a subgroup of individuals with elevated amyloid, suggesting that it is detrimental, rather than compensatory in nature.

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A multi-center study: Intra-scan and inter-scan variability of diffusion spectrum imaging.

Publication Date: 2012 May 1 PMID: 22569062
Authors: Lemkaddem, A. - Daducci, A. - Vulliemoz, S. - O'Brien, K. - Lazeyras, F. - Hauf, M. - Wiest, R. - Meuli, R. - Seeck, M. - Krueger, G. - Thiran, J. P.
Journal: Neuroimage

The objective of this study was to investigate whether it is possible to pool together diffusion spectrum imaging data from four different scanners, located at three different sites. Two of the scanners had identical configuration whereas two did not. To measure the variability, we extracted three scalar maps (ADC, FA and GFA) from the DSI and utilized a region and a tract-based analysis. Additionally, a phantom study was performed to rule out some potential factors arising from the scanner performance in case some systematic bias occurred in the subject study. This work was split into three experiments: intra-scanner reproducibility, reproducibility with twin-scanner settings and reproducibility with other configurations. Overall for the intra-scanner and twin-scanner experiments, the region-based analysis coefficient of variation (CV) was in a range of 1%-4.2% and below 3% for almost every bundle for the tract-based analysis. The uncinate fasciculus showed the worst reproducibility, especially for FA and GFA values (CV 3.7-6%). For the GFA and FA maps, an ICC value of 0.7 and above is observed in almost all the regions/tracts. Looking at the last experiment, it was found that there is a very high similarity of the outcomes from the two scanners with identical setting. However, this was not the case for the two other imagers. Given the fact that the overall variation in our study is low for the imagers with identical settings, our findings support the feasibility of cross-site pooling of DSI data from identical scanners.

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Common and unique neuro-functional basis of induction, visualization, and spatial relationships as cognitive components of fluid intelligence.

Publication Date: 2012 May 4 PMID: 22565203
Authors: Ebisch, S. J. - Perrucci, M. G. - Mercuri, P. - Romanelli, R. - Mantini, D. - Romani, G. L. - Colom, R. - Saggino, A.
Journal: Neuroimage

Neuroimaging research of fluid intelligence (Gf) has mainly focused on the neural basis of abilities explaining performance on cognitive tasks. However, the neuro-functional basis of clearly defined theoretical cognitive components underlying Gf remains unclear. Induction, visualization, and spatial relationships have the highest relevance for Gf (Carroll, 1993). Here we report a functional magnetic resonance imaging (fMRI) study exploring the neural correlates of these abilities characterized by their unidimensionality and matched for task-difficulty, as evidenced by a psychometric calibration study. Twenty-two healthy young adult females, recruited from a large sample of 300 participants, with either below- or above-average Gf abilities underwent fMRI scanning during Gf task performance. The results reveal that these tasks activate a shared frontoparietal network. Specific activations were also observed, in particular for induction and visualization. The key findings suggest that Gf comprises distinguishable cognitive abilities, but the Gf construct is associated with a common network.

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So that's what you meant! Event-related potentials reveal multiple aspects of context use during construction of message-level meaning.

Publication Date: 2012 May 4 PMID: 22565202
Authors: Wlotko, E. W. - Federmeier, K. D.
Journal: Neuroimage

Factors that modulate the influence of contextual information on semantic processing in language comprehension have been thoroughly investigated with the N400 component of the event-related potential (ERP), a direct measure of initial contact with semantic memory. Although context has a strong and immediate impact on processing, multiple mechanisms contribute to the construction of message-level representations during normal comprehension. Some of these may be engaged after or concurrent with the formation of an initial meaning representation, and can then serve to revise or reshape meaning. In this study, ERPs were recorded while participants read plausible sentences that continuously varied in the amount of contextual constraint for the sentence-final word, defined via extensive norming data including the range of possible alternative completions for the contexts. Consistent with numerous past studies, the amplitude of the N400 was graded with expectancy, as amplitudes decreased with increasing constraint. Additionally, a left-lateralized, broad, slow negativity onsetting around 400-500ms was largest for sentences with moderately strong constraint. Within this range of constraint, the negativity was larger for sentences with fewer alternative completions compared to those with many different ones. The timing and scalp distribution of the effect resemble brain responses linked to engagement of working memory resources, ambiguity resolution, and comprehension of jokes. Similar to cases of "frame-shifting" in non-literal language, this effect may reflect processing associated with reinterpretation or reconsideration of contextual material when multiple interpretations of a sentence were likely.

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Tracking neural coding of perceptual and semantic features of concrete nouns.

Publication Date: 2012 May 4 PMID: 22565201
Authors: Sudre, G. - Pomerleau, D. - Palatucci, M. - Wehbe, L. - Fyshe, A. - Salmelin, R. - Mitchell, T.
Journal: Neuroimage

We present a methodological approach employing magnetoencephalography (MEG) and machine learning techniques to investigate the flow of perceptual and semantic information decodable from neural activity in the half second during which the brain comprehends the meaning of a concrete noun. Important information about the cortical location of neural activity related to the representation of nouns in the human brain has been revealed by past studies using fMRI. However, the temporal sequence of processing from sensory input to concept comprehension remains unclear, in part because of the poor time resolution provided by fMRI. In this study, subjects answered 20 questions (e.g. is it alive?) about the properties of 60 different nouns prompted by simultaneous presentation of a pictured item and its written name. Our results show that the neural activity observed with MEG encodes a variety of perceptual and semantic features of stimuli at different times relative to stimulus onset, and in different cortical locations. By decoding these features, our MEG-based classifier was able to reliably distinguish between two different concrete nouns that it had never seen before. The results demonstrate that there are clear differences between the time course of the magnitude of MEG activity and that of decodable semantic information. Perceptual features were decoded from MEG activity earlier in time than semantic features, and features related to animacy, size, and manipulability were decoded consistently across subjects. We also observed that regions commonly associated with semantic processing in the fMRI literature may not show high decoding results in MEG. We believe that this type of approach and the accompanying machine learning methods can form the basis for further modeling of the flow of neural information during language processing and a variety of other cognitive processes.

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The development and future of perfusion fMRI for dynamic imaging of human brain activity.

Publication Date: 2012 Apr 26 PMID: 22562056
Authors: Aguirre, G. K. - Detre, J. A.
Journal: Neuroimage

Arterial spin labeled (ASL), perfusion fMRI was developed nearly simultaneously with BOLD fMRI. The application of this technique in studies of human brain activity has grown slowly over the last twenty years, primarily because of the need to meet technical challenges in data acquisition and analysis. Even within these constraints, perfusion fMRI has been identified as a tool that is well suited to measure slow changes in neural activity and to examine individual differences in brain-behavior relationships. Major advances have been made in acquisition and analysis techniques during this time. With further, anticipated technical improvements, perfusion fMRI studies in humans are poised to gain the improved cortical spatial resolution that has been observed in animal studies. If achieved, these advances portend surprising future applications of perfusion fMRI, including multi-voxel pattern analysis.

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Neural plasticity associated with recently versus often heard objects.

Publication Date: 2012 May 4 PMID: 22561412
Authors: Bourquin, N. M. - Spierer, L. - Murray, M. M. - Clarke, S.
Journal: Neuroimage

In natural settings the same sound source is often heard repeatedly, with variations in spectro-temporal and spatial characteristics. We investigated how such repetitions influence sound representations and in particular how auditory cortices keep track of recently vs. often heard objects. A set of 40 environmental sounds was presented twice, i.e. as prime and as repeat, while subjects categorized the corresponding sound sources as living vs. non-living. Electrical neuroimaging analyses were applied to auditory evoked potentials (AEPs) comparing primes vs. repeats (effect of presentation) and the four experimental sections. Dynamic analysis of distributed source estimations revealed i) a significant main effect of presentation within the left temporal convexity at 164-215ms post-stimulus onset; and ii) a significant main effect of section in the right temporo-parietal junction at 166-213ms. A 3-way repeated measures ANOVA (hemispherexpresentationxsection) applied to neural activity of the above clusters during the common time window confirmed the specificity of the left hemisphere for the effect of presentation, but not that of the right hemisphere for the effect of section. In conclusion, spatio-temporal dynamics of neural activity encode the temporal history of exposure to sound objects. Rapidly occurring plastic changes within the semantic representations of the left hemisphere keep track of objects heard a few seconds before, independent of the more general sound exposure history. Progressively occurring and more long-lasting plastic changes occurring predominantly within right hemispheric networks, which are known to code for perceptual, semantic and spatial aspects of sound objects, keep track of multiple exposures.

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Enhanced sensory processing accompanies successful detection of change for real-world sounds.

Publication Date: 2012 May 4 PMID: 22561411
Authors: Gregg, M. K. - Snyder, J. S.
Journal: Neuroimage

Change deafness is the inability of listeners to detect changes occurring in their auditory environment. It is a matter of some debate whether change deafness occurs because of a failure of auditory-specific processes or a failure of more general semantic/verbal memory. To address this issue, we measured event-related potentials (ERPs) to pairs of scenes consisting of naturalistic auditory objects while listeners made a same/different judgment for scenes presented before and after an interruption. ERPs to the post-change scene revealed an enhanced early sensory response (N1) and an enhanced late positivity (P3) for detected changes. Change detection performance was better when there was a large acoustic spread among the objects within Scenes 1 and 2, suggesting that the deficits reflected by the ERP components during change deafness are related to successfully segregating the pre- and post-change objects. We also found that a separate sensory response (P2) reflects implicit, unconscious change detection. Overall, the results provide evidence that auditory-specific sensory processing is critical for both explicit and implicit change detection in natural auditory scenes.

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The heritability of brain metabolites on proton magnetic resonance spectroscopy in older individuals.

Publication Date: 2012 Apr 27 PMID: 22561359
Authors: Batouli, S. A. - Sachdev, P. S. - Wen, W. - Wright, M. J. - Suo, C. - Ames, D. - Trollor, J. N.
Journal: Neuroimage

Twin studies have shown that many aspects of brain structure are heritable, suggesting a strong genetic contribution to brain structure. Less is known about functional aspects of the brain, in particular biologically relevant metabolites in the brain such as those measured by proton magnetic resonance spectroscopy (((1))H MRS), N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho) and myoinositol (ml), which have been suggested as possible markers of brain aging and early dementia. We examined 296 (56 male/108 female monozygotic and 43 male/89 female dizygotic) older twins (mean age 72.2+/-5.5years, range 65-88), for the levels of these metabolites relative to the H(2)O signal in the posterior cingulate cortex using ((1))H MRS. All metabolites showed substantial heritability, which was greatest for the neuronal integrity marker NAA (72%), and less so for the others - Cr (51%), Cho (33%) and ml (55%). The heritability of these markers did not change significantly with age or sex. The genetic determination of NAA, along with the evidence that NAA levels change in aging and neurodegenerative diseases suggest that it is a potential endophenotype of brain aging and dementia.

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Mapping magnetic susceptibility anisotropies of white matter in vivo in the human brain at 7T.

Publication Date: 2012 Apr 28 PMID: 22561358
Authors: Li, X. - Vikram, D. S. - Lim, I. A. - Jones, C. K. - Farrell, J. A. - van Zijl, P. C.
Journal: Neuroimage

High-resolution magnetic resonance phase- or frequency-shift images acquired at high field show contrast related to magnetic susceptibility differences between tissues. Such contrast varies with the orientation of the organ in the field, but the development of quantitative susceptibility mapping (QSM) has made it possible to reproducibly image the intrinsic tissue susceptibility contrast. However, recent studies indicate that magnetic susceptibility is anisotropic in brain white matter and, as such, needs to be described by a symmetric second-rank tensor (chi ). To fully determine the elements of this tensor, it would be necessary to acquire frequency data at six or more orientations. Assuming cylindrical symmetry of the susceptibility tensor in myelinated white matter fibers, we propose a simplified method to reconstruct the susceptibility tensor in terms of a mean magnetic susceptibility, MMS=(chi(//)+2chi( perpendicular))/3 and a magnetic susceptibility anisotropy, MSA=chi(//)-chi( perpendicular), where chi(//) and chi( perpendicular) are susceptibility parallel and perpendicular to the white matter fiber direction, respectively. Computer simulations show that with a practical head rotation angle of around 20 degrees -30 degrees , four head orientations suffice to reproducibly reconstruct the tensor with good accuracy. We tested this approach on whole brain 1x1x1mm(3) frequency data acquired from five healthy subjects at 7T. The frequency information from phase images collected at four head orientations was combined with the fiber direction information extracted from diffusion tensor imaging (DTI) to map the white matter susceptibility tensor. The MMS and MSA were quantified for regions in several large white matter fiber structures, including the corona radiata, posterior thalamic radiation and corpus callosum. MMS ranged from -0.037 to -0.053ppm (referenced to CSF being about zero). MSA values could be quantified without the need for a reference and ranged between 0.004 and 0.029ppm, in line with the expectation that the susceptibility perpendicular to the fiber is more diamagnetic than the one parallel to it.

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Separating neural and vascular effects of caffeine using simultaneous EEG-FMRI: Differential effects of caffeine on cognitive and sensorimotor brain responses.

Publication Date: 2012 Apr 28 PMID: 22561357
Authors: Diukova, A. - Ware, J. - Smith, J. E. - Evans, J. C. - Murphy, K. - Rogers, P. J. - Wise, R. G.
Journal: Neuroimage

The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A(1) and A(2A) adenosine receptors resulting in increased neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, can modify BOLD FMRI signal responses through both its neural and its vascular effects depending on receptor distributions in different brain regions. In this study we aim to distinguish neural and vascular influences of a single dose of caffeine in measurements of task-related brain activity using simultaneous EEG-FMRI. We chose to compare low-level visual and motor (paced finger tapping) tasks with a cognitive (auditory oddball) task, with the expectation that caffeine would differentially affect brain responses in relation to these tasks. To avoid the influence of chronic caffeine intake, we examined the effect of 250mg of oral caffeine on 14 non and infrequent caffeine consumers in a double-blind placebo-controlled cross-over study. Our results show that the task-related BOLD signal change in visual and primary motor cortex was significantly reduced by caffeine, while the amplitude and latency of visual evoked potentials over occipital cortex remained unaltered. However, during the auditory oddball task (target versus non-target stimuli) caffeine significantly increased the BOLD signal in frontal cortex. Correspondingly, there was also a significant effect of caffeine in reducing the target evoked response potential (P300) latency in the oddball task and this was associated with a positive potential over frontal cortex. Behavioural data showed that caffeine also improved performance in the oddball task with a significantly reduced number of missed responses. Our results are consistent with earlier studies demonstrating altered flow-metabolism coupling after caffeine administration in the context of our observation of a generalised caffeine-induced reduction in cerebral blood flow demonstrated by arterial spin labelling (19% over grey matter). We were able to identify vascular effects and hence altered neurovascular coupling through the alteration of low-level task FMRI responses in the face of a preserved visual evoked potential. However, our data also suggest a cognitive effect of caffeine through its positive effect on the frontal BOLD signal consistent with the shortening of oddball EEG response latency. The combined use of EEG-FMRI is a promising methodology for investigating alterations in brain function in drug and disease studies where neurovascular coupling may be altered on a regional basis.

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Magneto- and electroencephalographic manifestations of reward anticipation and delivery.

Publication Date: 2012 Apr 26 PMID: 22561022
Authors: Donamayor, N. - Schoenfeld, M. A. - Munte, T. F.
Journal: Neuroimage

The monetary incentive delay task was used to characterize reward anticipation and delivery with concurrently acquired evoked magnetic fields, EEG potentials and EEG/MEG oscillatory responses, obtaining a precise portrayal of their spatiotemporal evolution. In the anticipation phase, differential activity was most prominent over midline electrodes and parieto-occipital sensors. Differences between non-reward- and reward-predicting cues were localized in the cuneus and later in the dorsal PCC, suggesting a modulation by potential reward information during early visual processing, followed by a coarse emotional evaluation of the cues. Oscillatory analysis revealed increased theta power after non-reward cues over fronto-central sites. In the beta range, power decreased with the magnitude of the potential reward and increased with reaction time, probably reflecting the influence of the striatal response to potential reward on the sensorimotor cortex. At reward delivery, negative prediction errors led to a larger mediofrontal negativity. The spatiotemporal evolution of reward processing was modulated by prediction error: whereas differences were located in PCC and putamen in the prediction error comparison, in the case of expected outcomes they were located in PCC, ACC and parahippocampal gyrus. In the oscillatory realm, theta power was largest following rewards and, in the case of non-rewards, was largest when these were unexpected. Higher beta activity following rewards was also observed in both modalities, but MEG additionally showed a significant power decrease for this condition over parieto-occipital sensors. Our results show how visual, limbic and striatal structures are involved in the different stages of reward anticipation and delivery, and how theta and beta oscillations have a prominent role in the processing of these stimuli.

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Pet imaging of cholinergic deficits in rats using [(18)F]fluoroethoxybenzovesamicol ([(18)F]FEOBV).

Publication Date: 2012 Apr 25 PMID: 22555071
Authors: Parent, M. - Bedard, M. A. - Aliaga, A. - Soucy, J. P. - St-Pierre, E. L. - Cyr, M. - Massarweh, G. - Rosa-Neto, P.
Journal: Neuroimage

[(18)F]fluoroethoxybenzovesamicol ([(18)F]FEOBV) is one of the most promising radioligands for imaging the vesicular ACh transporter (VAChT) with positron emission tomography (PET). We report here that this method can detect subtle cholinergic terminals losses such as those associated with aging, or those following a partial lesion of the nucleus basalis magnocellularis (NBM). Twenty-one adult rats were evenly distributed in three groups including 1) aged rats (18months); 2) young rats (3months); and 3) rats with unilateral lesion of the NBM, following a local stereotaxic infusion of 192 IgG-saporin. In both normal and lesioned rats, our results revealed the highest [(18)F]FEOBV binding to be in the striatum, followed by similar values in both frontal cortex and thalamus, while lower values were observed in both hippocampus and temporo-parietal cortex. This binding distribution is consistent with the known anatomy of brain cholinergic systems. In the lesioned rats, [(18)F]FEOBV binding was found to be reduced mostly in the ventral frontal cortex on the side of the lesion, but some reductions were also observed in the homologous region of the contralateral hemisphere. Aging was found to be associated with a [(18)F]FEOBV binding reduction limited to the hippocampus of both hemispheres. [(18)F]FEOBV appears to be a very promising marker for the in vivo quantification of the brain VAChT; PET imaging of this agent allows in vivo detection of both physiological and pathological reductions of cholinergic terminals density.

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Go and no-go learning in reward and punishment: Interactions between affect and effect.

Publication Date: 2012 Apr 21 PMID: 22548809
Authors: Guitart-Masip, M. - Huys, Q. J. - Fuentemilla, L. - Dayan, P. - Duzel, E. - Dolan, R. J.
Journal: Neuroimage

Decision-making invokes two fundamental axes of control: affect or valence, spanning reward and punishment, and effect or action, spanning invigoration and inhibition. We studied the acquisition of instrumental responding in healthy human volunteers in a task in which we orthogonalized action requirements and outcome valence. Subjects were much more successful in learning active choices in rewarded conditions, and passive choices in punished conditions. Using computational reinforcement-learning models, we teased apart contributions from putatively instrumental and Pavlovian components in the generation of the observed asymmetry during learning. Moreover, using model-based fMRI, we showed that BOLD signals in striatum and substantia nigra/ventral tegmental area (SN/VTA) correlated with instrumentally learnt action values, but with opposite signs for go and no-go choices. Finally, we showed that successful instrumental learning depends on engagement of bilateral inferior frontal gyrus. Our behavioral and computational data showed that instrumental learning is contingent on overcoming inherent and plastic Pavlovian biases, while our neuronal data showed this learning is linked to unique patterns of brain activity in regions implicated in action and inhibition respectively.

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Examining ERP correlates of recognition memory: Evidence of accurate source recognition without recollection.

Publication Date: 2012 Apr 25 PMID: 22548808
Authors: Addante, R. J. - Ranganath, C. - Yonelinas, A. P.
Journal: Neuroimage

Recollection is typically associated with high recognition confidence and accurate source memory. However, subjects sometimes make accurate source memory judgments even for items that are not confidently recognized, and it is not known whether these responses are based on recollection or some other memory process. In the current study, we measured event related potentials (ERPs) while subjects made item and source memory confidence judgments in order to determine whether recollection supported accurate source recognition responses for items that were not confidently recognized. In line with previous studies, we found that recognition memory was associated with two ERP effects: an early on-setting FN400 effect, and a later parietal old-new effect [late positive component (LPC)], which have been associated with familiarity and recollection, respectively. The FN400 increased gradually with item recognition confidence, whereas the LPC was only observed for highly confident recognition responses. The LPC was also related to source accuracy, but only for items that had received a high confidence item recognition response; accurate source judgments to items that were less confidently recognized did not exhibit the typical ERP correlate of recollection or familiarity, but rather showed a late, broadly distributed negative ERP difference. The results indicate that accurate source judgments of episodic context can occur even when recollection fails.

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Equality versus self-interest in the brain: Differential roles of anterior insula and medial prefrontal cortex.

Publication Date: 2012 Apr 23 PMID: 22548807
Authors: Civai, C. - Crescentini, C. - Rustichini, A. - Rumiati, R. I.
Journal: Neuroimage

Everything else being the same, an equal outcome is generally preferred; however, an equitable allocation sometimes is possible only by sacrificing the total amount of resources available to society. Moreover, direct interests may interact with the perception of equality. Here, we have investigated individual preferences, and their neural basis, by employing a task in which an allocation of a fixed amount between the subject and another person (MS condition) or two third parties (TP condition) is randomly determined. The subject can accept or reject the outcome, in the same fashion as the Ultimatum Game: thus an unequal offer may be rejected at the cost of a loss in total amount. Behavioral results show preference for equal outcomes in TP and for equal and advantageous outcomes in MS. An activation of medial prefrontal cortex (mPFC), extending to the anterior middle cingulate cortex (aMCC), was found in MS unequal outcomes, particularly for disadvantageous outcomes and consequent rejections. The anterior insula (AI) was active for unequal outcomes, in both MS and TP. We propose that the equal treatment is a default social norm, and its violation is signaled by the AI, whereas aMCC/mPFC activation, negatively correlated to rejections, reflects the effort to overcome the default rule of equal treatment in favor of a self-advantageous efficiency.

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Coupling and robustness of intra-cortical vascular territories.

Publication Date: 2012 Apr 24 PMID: 22548806
Authors: Guibert, R. - Fonta, C. - Risser, L. - Plouraboue, F.
Journal: Neuroimage

Vascular domains have been described as being coupled to neuronal functional units enabling dynamic blood supply to the cerebral cyto-architecture. Recent experiments have shown that penetrating arterioles of the grey matter are the building blocks for such units. Nevertheless, vascular territories are still poorly known, as the collection and analysis of large three-dimensional micro-vascular networks are difficult. By using an exhaustive reconstruction of the micro-vascular network in an 18mm(3) volume of marmoset cerebral cortex, we numerically computed the blood flow in each blood vessel. We thus defined arterial and venular territories and examined their overlap. A large part of the intracortical vascular network was found to be supplied by several arteries and drained by several venules. We quantified this multiple potential to compensate for deficiencies by introducing a new robustness parameter. Robustness proved to be positively correlated with cortical depth and a systematic investigation of coupling maps indicated local patterns of overlap between neighbouring arteries and neighbouring venules. However, arterio-venular coupling did not have a spatial pattern of overlap but showed locally preferential functional coupling, especially of one artery with two venules, supporting the notion of vascular units. We concluded that intra-cortical perfusion in the primate was characterised by both very narrow functional beds and a large capacity for compensatory redistribution, far beyond the nearest neighbour collaterals.

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"The archeologist's career ended in ruins": Hemispheric differences in pun comprehension in autism.

Publication Date: 2012 Apr 24 PMID: 22548805
Authors: Kana, R. K. - Wadsworth, H. M.
Journal: Neuroimage

Appropriate interpretation of figurative language involves inferring the speaker's intent by integrating word meaning with context. In disorders like autism, understanding intended and contextual meanings in language may pose a challenge. Such difficulties are prevalent even when individuals exhibit otherwise fluent language ability (Szatmari et al., 1990). A pun is a rhetorical technique in which a speaker deliberately invokes multiple meanings through a word or phrase likely resulting in a joke. Comprehending puns may involve identifying multiple meanings of a word, embedding it in right contexts, and understanding the underlying humor. This fMRI study investigated the brain responses associated with figures of speech like puns. In the fMRI scanner, participants read sentences containing puns (e.g. To write with a broken pencil is pointless) and control sentences (literal meaning) presented in a blocked design format. The participants' task was to silently read and understand one meaning (in the literal condition) or two meanings (in the pun condition). Participants with autism, relative to typical controls, showed an increase in overall activation while comprehending sentences containing puns, particularly within the right hemisphere as well as in relatively posterior brain areas. Overall, there was reduced response in left hemisphere areas, reduced response to humor, and more distributed recruitment of regions in autism relative to control participants. We also examined the relationship between symptom severity in autism and verbal ability with brain responses to pun comprehension finding negative and positive correlations respectively. Overall, the results from the present study suggest that individuals with autism resort to altered neural routes in comprehending language in general, and figurative language in particular.

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Effect of relevance on amygdala activation and association with the ventral striatum.

Publication Date: 2012 Apr 23 PMID: 22546319
Authors: Ousdal, O. T. - Reckless, G. E. - Server, A. - Andreassen, O. A. - Jensen, J.
Journal: Neuroimage

While the amygdala historically has been implicated in emotional stimuli processing, recent data suggest a general role in parceling out the relevance of stimuli, regardless of their emotional properties. Using functional magnetic resonance imaging, we tested the relevance hypothesis by investigating human amygdala responses to emotionally neutral stimuli while manipulating their relevance. The task was operationalized as highly relevant if a subsequent opportunity to respond for a reward depended on response accuracy of the task, and less relevant if the reward opportunity was independent of task performance. A region of interest analysis revealed bilateral amygdala activations in response to the high relevance condition compared to the low relevance condition. An exploratory whole-brain analysis yielded robust similar results in bilateral ventral striatum. A subsequent functional connectivity analysis demonstrated increased connectivity between amygdala and ventral striatum for the highly relevant stimuli compared to the less relevant stimuli. These findings suggest that the amygdala's processing profile goes beyond detection of emotions per se, and directly support the proposed role in relevance detection. In addition, the findings suggest a close relationship between amygdala and ventral striatal activity when processing relevant stimuli. Thus, the results may indicate that human amygdala modulates ventral striatum activity and subsequent behaviors beyond that observed for emotional cues, to encompass a broader range of relevant stimuli.

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Calibrating the BOLD signal during a motor task using an extended fusion model incorporating DOT, BOLD and ASL data.

Publication Date: 2012 Apr 23 PMID: 22546318
Authors: Yucel, M. A. - Huppert, T. J. - Boas, D. A. - Gagnon, L.
Journal: Neuroimage

Multimodal imaging improves the accuracy of the localization and the quantification of brain activation when measuring different manifestations of the hemodynamic response associated with cerebral activity. In this study, we incorporated cerebral blood flow (CBF) changes measured with arterial spin labeling (ASL), Diffuse Optical Tomography (DOT) and blood oxygen level-dependent (BOLD) recordings to reconstruct changes in oxy- (DeltaHbO(2)) and deoxyhemoglobin (DeltaHbR). Using the Grubb relation between relative changes in CBF and cerebral blood volume (CBV), we incorporated the ASL measurement as a prior to the total hemoglobin concentration change (DeltaHbT). We applied this ASL fusion model to both synthetic data and experimental multimodal recordings during a 2-s finger-tapping task. Our results show that the new approach is very powerful in estimating DeltaHbO(2) and DeltaHbR with high spatial and quantitative accuracy. Moreover, our approach allows the computation of baseline total hemoglobin concentration (HbT(0)) as well as of the BOLD calibration factor M on a single subject basis. We obtained an average HbT(0) of 71muM, an average M value of 0.18 and an average increase of 13% in cerebral metabolic rate of oxygen (CMRO(2)), all of which are in agreement with values previously reported in the literature. Our method yields an independent measurement of M, which provides an alternative measurement to validate the hypercapnic calibration of the BOLD signal.

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Neuroimaging differences between older adults with maintained versus declining cognition over a 10-year period.

Publication Date: 2012 Apr 20 PMID: 22542701
Authors: Rosano, C. - Aizenstein, H. J. - Newman, A. B. - Venkatraman, V. - Harris, T. - Ding, J. - Satterfield, S. - Yaffe, K.
Journal: Neuroimage

BACKGROUND: Maintaining cognitive function protects older adults from developing functional decline. This study aims to identify the neuroimaging correlates of maintenance of higher global cognition as measured by the Modified Mini Mental State Test (3MS) score. METHODS: Repeated 3MS measures from 1997-98 through 2006-07 and magnetic resonance imaging with diffusion tensor in 2006-07 were obtained in a biracial cohort of 258 adults free from dementia (mean age 82.9years, 56% women, 42% blacks). Participants were classified as having shown either maintenance (3MS slope>0) or decline (3MS slope<1SD below the mean) of cognition using linear mixed models. Measures of interest were white matter hyperintensity volume (WMHv) from total brain, volume of the gray matter (GMv) and microstructure (mean diffusivity, MD) for total brain and for brain areas known to be related to memory and executive control function: medial temporal area (hippocampus, parahippocampus and entorhinal cortex), cingulate cortex, dorsolateral prefrontal and posterior parietal cortex. RESULTS: Differences between cognitive maintainers (n=153) and non-maintainers (n=107) were significant for GMv of the medial temporal area (35.8%, p=0.004) and lower MD of the cingulate cortex (37.9%, p=0.008), but not for other neuroimaging markers. In multivariable regression models adjusted for age, race, WMHv and GMV from the total brain and vascular conditions, each standard deviation of GMv of the medial temporal area and each standard deviation of MD of the cingulate cortex were associated with a nearly 4 times greater probability (odds ratio [standard deviation]: 3.80 [1.16, 12.44]) and a 34% lower probability (0.66, [0.46, 0.97]) of maintaining cognitive function, respectively. In these models neither WMHv nor GMv from total brain were significantly associated with probability of maintaining cognitive function. CONCLUSIONS: Preserving the volume of the medial temporal area and the microstructure of the cingulate cortex may contribute to maintaining cognitive function late in life.

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An automatic MEG low-frequency source imaging approach for detecting injuries in mild and moderate TBI patients with blast and non-blast causes.

Publication Date: 2012 Apr 20 PMID: 22542638
Authors: Huang, M. X. - Nichols, S. - Robb, A. - Angeles, A. - Drake, A. - Holland, M. - Asmussen, S. - D'Andrea, J. - Chun, W. - Levy, M. - Cui, L. - Song, T. - Baker, D. G. - Hammer, P. - McLay, R. - Theilmann, R. J. - Coimbra, R. - Diwakar, M. - Boyd, C. - Neff, J. - Liu, T. T. - Webb-Murphy, J. - Farinpour, R. - Cheung, C. - Harrington, D. L. - Heister, D. - Lee, R. R.
Journal: Neuroimage

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. Injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4Hz) that can be measured and localized by magnetoencephalography (MEG). We developed a new automated MEG low-frequency source imaging method and applied this method in 45 mild TBI (23 from combat-related blasts, and 22 from non-blast causes) and 10 moderate TBI patients (non-blast causes). Seventeen of the patients with mild TBI from blasts had tertiary injuries resulting from the blast. The results show our method detected abnormalities at the rates of 87% for the mild TBI group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities were 96% and 77% for the blast and non-blast TBI groups, respectively. The spatial characteristics of abnormal slow-wave generation measured by Z scores in the mild blast TBI group significantly correlated with those in non-blast mild TBI group. Among 96 cortical regions, the likelihood of abnormal slow-wave generation was less in the mild TBI patients with blast than in the mild non-blast TBI patients, suggesting possible protective effects due to the military helmet and armor. Finally, the number of cortical regions that generated abnormal slow-waves correlated significantly with the total post-concussive symptom scores in TBI patients. This study provides a foundation for using MEG low-frequency source imaging to support the clinical diagnosis of TBI.

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Twenty years of functional MRI: The science and the stories.

Publication Date: 2012 Apr 20 PMID: 22542637
Authors: Bandettini, P. A.
Journal: Neuroimage

Since its inception over twenty years ago, the field of functional magnetic resonance imaging (fMRI) has grown in usage, sophistication, range of applications, and impact. After twenty years, it's useful to briefly look back as well as forward - to size up just how far we have come and speculate just how far we may go. This is an introduction to the special issue of "Twenty years of fMRI: the science and the stories." The one-hundred and three papers in this special issue highlight the major methodological developments and controversies of fMRI from a first person perspective over the past twenty years. The growth of this field is not just fascinating from a science and technology perspective, but also from a human perspective. Most who were fortunate enough to be part of this effort at the beginning, as well as those who jumped in along the way have their fair share of interesting stories consisting of top rate science as well as intense thought and effort, good or bad fortune, and some claim to a contribution. These stories are in the following papers, written by the current leaders in the field and the innovators throughout the twenty year history. The categories, designed to cover every aspect of the emergence and development of fMRI, include: pre-fMRI; the first BOLD brain activation results; developments in pulse sequences, imaging methods, and hardware for fMRI; methodological developments, issues, and mechanisms; new paradigm designs; education; and the future. Within this issue, we have a collage of overlapping, complementary, yet sometimes contradictory accounts of what happened during the breathtakingly diverse and intense development of this still growing field over the past twenty years.

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Manipulations of cognitive strategies and intergroup relationships reduce the racial bias in empathic neural responses.

Publication Date: 2012 Apr 20 PMID: 22542636
Authors: Sheng, F. - Han, S.
Journal: Neuroimage

Social relationships affect empathy in humans such that empathic neural responses to perceived pain were stronger to racial in-group members than to racial out-group members. Why does the racial bias in empathy (RBE) occur and how can we reduce it? We hypothesized that perceiving an other-race person as a symbol of a racial group, rather than as an individual, decreases references to his/her personal situation and weakens empathy for that person. This hypothesis predicts that individuating other-race persons by increasing attention to each individual's feelings or enclosing other-race individuals within one's own social group can reduce the RBE by increasing empathic neural responses to other-race individuals. In Experiment 1, we recorded event related brain potentials from Chinese adults as they made race judgments on Asian and Caucasian faces with pain or neutral expressions. We identified the RBE by showing that, relative to neutral expressions, pain expressions increased neural responses at 128-188ms after stimulus onset over the frontal/central brain regions, and this effect was evident for same-race faces but not for other-race faces. Experiments 2 and 3 found that paying attention to observed individual's feelings of pain and including other-race individuals in one's own team for competitions respectively eliminated the RBE by increasing neural responses to pain expressions in other-race faces. Our results indicate that the RBE is not inevitable and that manipulations of both cognitive strategies and intergroup relationships can decrease RBE-related brain activity.

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Multimodal human communication--targeting facial expressions, speech content and prosody.

Publication Date: 2012 May 1 PMID: 22487549
Authors: Regenbogen, C. - Schneider, D. A. - Gur, R. E. - Schneider, F. - Habel, U. - Kellermann, T.
Journal: Neuroimage

Human communication is based on a dynamic information exchange of the communication channels facial expressions, prosody, and speech content. This fMRI study elucidated the impact of multimodal emotion processing and the specific contribution of each channel on behavioral empathy and its prerequisites. Ninety-six video clips displaying actors who told self-related stories were presented to 27 healthy participants. In two conditions, all channels uniformly transported only emotional or neutral information. Three conditions selectively presented two emotional channels and one neutral channel. Subjects indicated the actors' emotional valence and their own while fMRI was recorded. Activation patterns of tri-channel emotional communication reflected multimodal processing and facilitative effects for empathy. Accordingly, subjects' behavioral empathy rates significantly deteriorated once one source was neutral. However, emotionality expressed via two of three channels yielded activation in a network associated with theory-of-mind-processes. This suggested participants' effort to infer mental states of their counterparts and was accompanied by a decline of behavioral empathy, driven by the participants' emotional responses. Channel-specific emotional contributions were present in modality-specific areas. The identification of different network-nodes associated with human interactions constitutes a prerequisite for understanding dynamics that underlie multimodal integration and explain the observed decline in empathy rates. This task might also shed light on behavioral deficits and neural changes that accompany psychiatric diseases.

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Diminished performance on neuropsychological testing in late life depression is correlated with microstructural white matter abnormalities.

Publication Date: 2012 May 1 PMID: 22487548
Authors: Mettenburg, J. M. - Benzinger, T. L. - Shimony, J. S. - Snyder, A. Z. - Sheline, Y. I.
Journal: Neuroimage

BACKGROUND: Traditional T2 weighted MR imaging results are non-specific for the extent of underlying white matter structural abnormalities present in late life depression (LLD). Diffusion tensor imaging provides a unique opportunity to investigate the extent and nature of structural injury, but has been limited by examining only a subset of regions of interest (ROI) and by confounds common to the study of an elderly population, including comorbid vascular pathology. Furthermore, comprehensive correlation of diffusion tensor imaging (DTI) measurements, including axial and radial diffusivity measurements, has not been demonstrated in the late life depression population. METHODS: 51 depressed and 16 non-depressed, age- and cerebrovascular risk factor-matched elderly subjects underwent traditional anatomic T1 and T2 weight imaging, as well as DTI. The DTI data were skeletonized using tract based spatial statistics (TBSS), and both regional and global analyses were performed. RESULTS: Widespread structural abnormalities within white matter were detected in the LLD group, accounting for age, gender and education and matched for cerebrovascular risk factors and global T2 white matter hyperintensities (T2WMH). Regional differences were most prominent in uncinate and cingulate white matter and were generally characterized by an increase in radial diffusivity. Age-related changes particularly in the cingulate bundle were more advanced in individuals with LLD relative to controls. Regression analysis demonstrated significant correlations of regional fractional anisotropy and radial diffusivity with five different neuropsychological factor scores. TBSS analysis demonstrated a greater extent of white matter abnormalities in LLD not responsive to treatment, as compared to controls. CONCLUSIONS: White matter integrity is compromised in late life depression, largely manifested by increased radial diffusivity in specific regions, suggesting underlying myelin injury. A possible mechanism for underlying myelin injury is chronic white matter ischemia related to intrinsic cerebrovascular disease. In some regions such as the cingulate bundle, the white matter injury related to late life depression appears to be independent of and compounded by age-related changes. The correlations with neuropsychological testing indicate the essential effects of white matter injury on functional status. Lastly, response to treatment may depend on the extent of white matter injury, suggesting a need for intact functional networks.

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Quantitative imaging of energy expenditure in human brain.

Publication Date: 2012 May 1 PMID: 22487547
Authors: Zhu, X. H. - Qiao, H. - Du, F. - Xiong, Q. - Liu, X. - Zhang, X. - Ugurbil, K. - Chen, W.
Journal: Neuroimage

Despite the essential role of the brain energy generated from ATP hydrolysis in supporting cortical neuronal activity and brain function, it is challenging to noninvasively image and directly quantify the energy expenditure in the human brain. In this study, we applied an advanced in vivo(31)P MRS imaging approach to obtain regional cerebral metabolic rates of high-energy phosphate reactions catalyzed by ATPase (CMR(ATPase)) and creatine kinase (CMR(CK)), and to determine CMR(ATPase) and CMR(CK) in pure gray mater (GM) and white mater (WM), respectively. It was found that both ATPase and CK rates are three times higher in GM than WM; and CMR(CK) is seven times higher than CMR(ATPase) in GM and WM. Among the total brain ATP consumption in the human cortical GM and WM, 77% of them are used by GM in which approximately 96% is by neurons. A single cortical neuron utilizes approximately 4.7 billion ATPs per second in a resting human brain. This study demonstrates the unique utility of in vivo(31)P MRS imaging modality for direct imaging of brain energy generated from ATP hydrolysis, and provides new insights into the human brain energetics and its role in supporting neuronal activity and brain function.

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The behavioral significance of coherent resting-state oscillations after stroke.

Publication Date: 2012 May 15 PMID: 22440653
Authors: Dubovik, S. - Pignat, J. M. - Ptak, R. - Aboulafia, T. - Allet, L. - Gillabert, N. - Magnin, C. - Albert, F. - Momjian-Mayor, I. - Nahum, L. - Lascano, A. M. - Michel, C. M. - Schnider, A. - Guggisberg, A. G.
Journal: Neuroimage

Stroke lesions induce not only loss of local neural function, but disruptions in spatially distributed areas. However, it is unknown whether they affect the synchrony of electrical oscillations in neural networks and if changes in network coherence are associated with neurological deficits. This study assessed these questions in a population of patients with subacute, unilateral, ischemic stroke. Spontaneous cortical oscillations were reconstructed from high-resolution electroencephalograms (EEG) with adaptive spatial filters. Maps of functional connectivity (FC) between brain areas were created and correlated with patient performance in motor and cognitive scores. In comparison to age matched healthy controls, stroke patients showed a selective disruption of FC in the alpha frequency range. The spatial distribution of alpha band FC reflected the pattern of motor and cognitive deficits of the individual patient: network nodes that participate normally in the affected functions showed local decreases in FC with the rest of the brain. Interregional FC in the alpha band, but not in delta, theta, or beta frequencies, was highly correlated with motor and cognitive performance. In contrast, FC between contralesional areas and the rest of the brain was negatively associated with patient performance. Alpha oscillation synchrony at rest is a unique and specific marker of network function and linearly associated with behavioral performance. Maps of alpha synchrony computed from a single resting-state EEG recording provide a robust and convenient window into the functionality and organization of cortical networks with numerous potential applications.

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Social grasping: From mirroring to mentalizing.

Publication Date: 2012 May 15 PMID: 22440652
Authors: Becchio, C. - Cavallo, A. - Begliomini, C. - Sartori, L. - Feltrin, G. - Castiello, U.
Journal: Neuroimage

Because the way we grasp an object varies depending on the intention with which the object is grasped, monitoring the properties of prehensile movements may provide access to a person's intention. Here we investigate the role of visual kinematics in the implicit coding of intention, by using functional brain imaging while participants observed grasping movements performed with social versus individual intents. The results show that activation within the mirror system is stronger during the observation of socially intended movements relative to individual movements. Moreover, areas that form the mentalizing system are more active during social grasping movements. These findings demonstrate that, in the absence of context information, social information conveyed by action kinematics modulates intention processing, leading to a transition from mirroring to mentalizing.

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Is optical imaging spectroscopy a viable measurement technique for the investigation of the negative BOLD phenomenon? A concurrent optical imaging spectroscopy and fMRI study at high field (7T).

Publication Date: 2012 May 15 PMID: 22440642
Authors: Kennerley, A. J. - Mayhew, J. E. - Boorman, L. - Zheng, Y. - Berwick, J.
Journal: Neuroimage

Traditionally functional magnetic resonance imaging (fMRI) has been used to map activity in the human brain by measuring increases in the Blood Oxygenation Level Dependent (BOLD) signal. Often accompanying positive BOLD fMRI signal changes are sustained negative signal changes. Previous studies investigating the neurovascular coupling mechanisms of the negative BOLD phenomenon have used concurrent 2D-optical imaging spectroscopy (2D-OIS) and electrophysiology (Boorman et al., 2010). These experiments suggested that the negative BOLD signal in response to whisker stimulation was a result of an increase in deoxy-haemoglobin and reduced multi-unit activity in the deep cortical layers. However, Boorman et al. (2010) did not measure the BOLD and haemodynamic response concurrently and so could not quantitatively compare either the spatial maps or the 2D-OIS and fMRI time series directly. Furthermore their study utilised a homogeneous tissue model in which is predominantly sensitive to haemodynamic changes in more superficial layers. Here we test whether the 2D-OIS technique is appropriate for studies of negative BOLD. We used concurrent fMRI with 2D-OIS techniques for the investigation of the haemodynamics underlying the negative BOLD at 7 Tesla. We investigated whether optical methods could be used to accurately map and measure the negative BOLD phenomenon by using 2D-OIS haemodynamic data to derive predictions from a biophysical model of BOLD signal changes. We showed that despite the deep cortical origin of the negative BOLD response, if an appropriate heterogeneous tissue model is used in the spectroscopic analysis then 2D-OIS can be used to investigate the negative BOLD phenomenon.

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A multi-modal investigation of behavioral adjustment: Post-error slowing is associated with white matter characteristics.

Publication Date: 2012 May 15 PMID: 22433658
Authors: Fjell, A. M. - Westlye, L. T. - Amlien, I. K. - Walhovd, K. B.
Journal: Neuroimage

When people make mistakes in speeded cognitive tasks, their response time on the next trial will typically be slower. This is referred to as post-error slowing (PES), and is important for optimization of performance, but its exact function remains to be decided. However, although PES is relatively stable over time, we have almost no knowledge about how PES is affected by structural brain characteristics. The aim of this study was to test to what extent white matter (WM) macro- and microstructure can account for individual differences in PES. PES was calculated for 255 healthy participants who performed a modified version of the Eriksen flanker task and underwent structural magnetic resonance imaging and diffusion tensor imaging (DTI). PES was positively related to WM volume in the caudal and rostral middle and superior frontal, medial orbitofrontal gyri and pars orbitalis. DTI analyses with tract-based spatial statistics (TBSS) showed that mean diffusivity in the superior longitudinal fasciculus, inferior fronto-occipital fasciculus and anterior thalamic radiation, as well as axial diffusivity in the corpus callosum, was negatively related to PES. Path analysis demonstrated that WM micro- and macrostructure were complementary in accounting for PES. It is concluded that individual differences in WM characteristics can partly explain why some people are better at adjusting their behavior in response to poor performance than others.

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Attenuation of long-range temporal correlations in the amplitude dynamics of alpha and beta neuronal oscillations in patients with schizophrenia.

Publication Date: 2012 May 15 PMID: 22430497
Authors: Nikulin, V. V. - Jonsson, E. G. - Brismar, T.
Journal: Neuroimage

Although schizophrenia was previously associated with affected spatial neuronal synchronization, surprisingly little is known about the temporal dynamics of neuronal oscillations in this disease. However, given that the coordination of neuronal processes in time represents an essential aspect of practically all cognitive operations, it might be strongly affected in patients with schizophrenia. In the present study we aimed at quantifying long-range temporal correlations (LRTC) in patients (18 with schizophrenia; 3 with schizoaffective disorder) and 28 healthy control subjects matched for age and gender. Ongoing neuronal oscillations were recorded with multi-channel EEG at rest condition. LRTC in the range 5-50s were analyzed with Detrended Fluctuation Analysis. The amplitude of neuronal oscillations in alpha and beta frequency ranges did not differ between patients and control subjects. However, LRTC were strongly attenuated in patients with schizophrenia in both alpha and beta frequency ranges. Moreover, the cross-frequency correlation between LRTC belonging to alpha and beta oscillations was stronger for patients than healthy controls, indicating that similar neurophysiological processes affect neuronal dynamics in both frequency ranges. We believe that the attenuation of LRTC is most likely due to the increased variability in neuronal activity, which was previously hypothesized to underlie an excessive switching between the neuronal states in patients with schizophrenia. Attenuated LRTC might allow for more random associations between neuronal activations, which in turn might relate to the occurrence of thought disorders in schizophrenia.

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A BOLD signature of eyeblinks in the visual cortex.

Publication Date: 2012 May 15 PMID: 22426351
Authors: Hupe, J. M. - Bordier, C. - Dojat, M.
Journal: Neuroimage

We are usually unaware of the brief but large illumination changes caused by blinks, presumably because of blink suppression mechanisms. In fMRI however, increase of the BOLD signal was reported in the visual cortex, e.g. during blocks of voluntary blinks (Bristow, Frith and Rees, 2005) or after spontaneous blinks recorded during the prolonged fixation of a static stimulus (Tse, Baumgartner and Greenlee, 2010). We tested whether such activation, possibly related to illumination changes, was also present during standard fMRI retinotopic and visual experiments and was large enough to contaminate the BOLD signal we are interested in. We monitored in a 3T scanner the eyeblinks of 14 subjects who observed three different types of visual stimuli, including periodic rotating wedges and contracting/expanding rings, event-related Mondrians and graphemes, while fixating. We performed event-related analyses on the set of detected spontaneous blinks. We observed large and widespread BOLD responses related to blinks in the visual cortex of every subject and whatever the visual stimulus. The magnitude of the modulation was comparable to visual stimulation. However, blink-related activations lay mostly in the anterior parts of retinotopic visual areas, coding the periphery of the visual field well beyond the extent of our stimuli. Blinks therefore represent an important source of BOLD variations in the visual cortex and a troublesome source of noise since any correlation, even weak, between the distribution of blinks and a tested protocol could trigger artifactual activities. However, the typical signature of blinks along the anterior calcarine and the parieto-occipital sulcus allows identifying, even in the absence of eyetracking, fMRI protocols possibly contaminated by a heterogeneous distribution of blinks.

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Effects of lactate on the early visual cortex of non-human primates, investigated by pharmaco-MRI and neurochemical analysis.

Publication Date: 2012 May 15 PMID: 22426350
Authors: von Pfostl, V. - Li, J. - Zaldivar, D. - Goense, J. - Zhang, X. - Serr, N. - Logothetis, N. K. - Rauch, A.
Journal: Neuroimage

In contrast to the limited use of functional magnetic resonance imaging (fMRI) in clinical diagnostics, it is currently a mainstay of neuroimaging in clinical and basic brain research. However, its non-invasive use in combination with its high temporal and spatial resolution would make fMRI a perfect diagnostic tool. We are interested in whether a pharmacological challenge imposed on the brain can be reliably traced by the blood oxygen level-dependent (BOLD) signal and possibly further exploited for diagnostics. We have chosen a systemic challenge with lactate and pyruvate to test whether the physiological formation of these monocarboxylic acids contributes to the BOLD signal and can be detected using fMRI. This information is also of interest because lactate levels in the cerebrospinal fluid rise concomitantly with reduced vascular responsiveness of the brain during the progression of Alzheimer disease (AD). We studied the BOLD response after a low-dose lactate challenge and monitored the induced plasma lactate levels in anesthetized non-human primates. We observed reliable lactate-induced BOLD responses, which could be confirmed at population and individual level by their strong correlation with systemic lactate concentrations. Comparable BOLD effects where observed after a slow infusion of pyruvate. We show here that physiological changes in lactate and pyruvate levels are indeed reflected in the BOLD signal, and describe the technical prerequisites to reliably trace a lactate challenge using BOLD-fMRI.

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Functional imaging correlates of impaired distractor suppression following sleep deprivation.

Publication Date: 2012 May 15 PMID: 22426349
Authors: Kong, D. - Soon, C. S. - Chee, M. W.
Journal: Neuroimage

Sleep deprivation (SD) has been shown to affect selective attention but it is not known how two of its component processes: target enhancement and distractor suppression, are affected. To investigate, young volunteers either attended to houses or were obliged to ignore them (when attending to faces) while viewing superimposed face-house pictures. MR signal enhancement and suppression in the parahippocampal place area (PPA) were determined relative to a passive viewing control condition. Sleep deprivation was associated with lower PPA activation across conditions. Critically SD specifically impaired distractor suppression in selective attention, leaving target enhancement relatively preserved. These findings parallel some observations in cognitive aging. Additionally, following SD, attended houses were not significantly better recognized than ignored houses in a post-experiment test of recognition memory contrasting with the finding of superior recognition of attended houses in the well-rested state. These results provide evidence for co-encoding of distracting information with targets into memory when one is sleep deprived.

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The physiological origin of task-evoked systemic artefacts in functional near infrared spectroscopy.

Publication Date: 2012 May 15 PMID: 22426347
Authors: Kirilina, E. - Jelzow, A. - Heine, A. - Niessing, M. - Wabnitz, H. - Bruhl, R. - Ittermann, B. - Jacobs, A. M. - Tachtsidis, I.
Journal: Neuroimage

A major methodological challenge of functional near-infrared spectroscopy (fNIRS) is its high sensitivity to haemodynamic fluctuations in the scalp. Superficial fluctuations contribute on the one hand to the physiological noise of fNIRS, impairing the signal-to-noise ratio, and may on the other hand be erroneously attributed to cerebral changes, leading to false positives in fNIRS experiments. Here we explore the localisation, time course and physiological origin of task-evoked superficial signals in fNIRS and present a method to separate them from cortical signals. We used complementary fNIRS, fMRI, MR-angiography and peripheral physiological measurements (blood pressure, heart rate, skin conductance and skin blood flow) to study activation in the frontal lobe during a continuous performance task. The General Linear Model (GLM) was applied to analyse the fNIRS data, which included an additional predictor to account for systemic changes in the skin. We found that skin blood volume strongly depends on the cognitive state and that sources of task-evoked systemic signals in fNIRS are co-localized with veins draining the scalp. Task-evoked superficial artefacts were mainly observed in concentration changes of oxygenated haemoglobin and could be effectively separated from cerebral signals by GLM analysis. Based on temporal correlation of fNIRS and fMRI signals with peripheral physiological measurements we conclude that the physiological origin of the systemic artefact is a task-evoked sympathetic arterial vasoconstriction followed by a decrease in venous volume. Since changes in sympathetic outflow accompany almost any cognitive and emotional process, we expect scalp vessel artefacts to be present in a wide range of fNIRS settings used in neurocognitive research. Therefore a careful separation of fNIRS signals originating from activated brain and from scalp is a necessary precondition for unbiased fNIRS brain activation maps.

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Very large fMRI study using the IMAGEN database: Sensitivity-specificity and population effect modeling in relation to the underlying anatomy.

Publication Date: 2012 May 15 PMID: 22425669
Authors: Thyreau, B. - Schwartz, Y. - Thirion, B. - Frouin, V. - Loth, E. - Vollstadt-Klein, S. - Paus, T. - Artiges, E. - Conrod, P. J. - Schumann, G. - Whelan, R. - Poline, J. B.
Journal: Neuroimage

In this paper we investigate the use of classical fMRI Random Effect (RFX) group statistics when analyzing a very large cohort and the possible improvement brought from anatomical information. Using 1326 subjects from the IMAGEN study, we first give a global picture of the evolution of the group effect t-value from a simple face-watching contrast with increasing cohort size. We obtain a wide activated pattern, far from being limited to the reasonably expected brain areas, illustrating the difference between statistical significance and practical significance. This motivates us to inject tissue-probability information into the group estimation, we model the BOLD contrast using a matter-weighted mixture of Gaussians and compare it to the common, single-Gaussian model. In both cases, the model parameters are estimated per-voxel for one subgroup, and the likelihood of both models is computed on a second, separate subgroup to reflect model generalization capacity. Various group sizes are tested, and significance is asserted using a 10-fold cross-validation scheme. We conclude that adding matter information consistently improves the quantitative analysis of BOLD responses in some areas of the brain, particularly those where accurate inter-subject registration remains challenging.

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Parametric imaging with Bayesian priors: A validation study with (11)C-Altropane PET.

Publication Date: 2012 May 15 PMID: 22425668
Authors: Dean Fang, Y. H. - El Fakhri, G. - Becker, J. A. - Alpert, N. M.
Journal: Neuroimage

It has been suggested that Bayesian estimation methods may be used to improve the signal-to-noise ratio of parametric images. However, there is little experience with the method and some of the underlying assumptions and performance properties of Bayesian estimation remain to be investigated. We used a sample population of 54 subjects, studied previously with (11)C-Altropane, to empirically evaluate the assumptions, performance and some practical issues in forming parametric images. By using normality tests, we showed that the underpinning normality assumptions of data and parametric distribution apply to more than 80% of voxels. The standard deviation of the binding potential can be reduced 30-50% using Bayesian estimation, without introducing substantial bias. The sample size required to form the a priori information was found to be modest; as little as ten subjects may be sufficient and the choice of specific subjects has little effect on Bayesian estimation. A realistic simulation study showed that detection of localized differences in parametric images, e.g. by statistical parametric mapping (SPM), could be made more reliable and/or conducted with smaller sample size using Bayesian estimation. In conclusion, Bayesian estimation can improve the SNR of parametric images and better detect localized changes in cohorts of subjects.

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Task-related BOLD responses and resting-state functional connectivity during physiological clamping of end-tidal CO(2).

Publication Date: 2012 May 15 PMID: 22418394
Authors: Madjar, C. - Gauthier, C. J. - Bellec, P. - Birn, R. M. - Brooks, J. C. - Hoge, R. D.
Journal: Neuroimage

Carbon dioxide (CO(2)), a potent vasodilator, is known to have a significant impact on the blood-oxygen level dependent (BOLD) signal. With the growing interest in studying synchronized BOLD fluctuations during the resting state, the extent to which the apparent synchrony is due to variations in the end-tidal pressure of CO(2) (PETCO(2)) is an important consideration. CO(2)-related fluctuations in BOLD signal may also represent a potential confound when studying task-related responses, especially if breathing depth and rate are affected by the task. While previous studies of the above issues have explored retrospective correction of BOLD fluctuations related to arterial PCO(2), here we demonstrate an alternative approach based on physiological clamping of the arterial CO(2) level to a near-constant value. We present data comparing resting-state functional connectivity within the default-mode-network (DMN), as well as task-related BOLD responses, acquired in two conditions in each subject: 1) while subject's PETCO(2) was allowed to vary spontaneously; and 2) while controlling subject's PETCO(2) within a narrow range. Strong task-related responses and areas of maximal signal correlation in the DMN were not significantly altered by suppressing fluctuations in PETCO(2). Controlling PETCO(2) did, however, improve the performance of retrospective physiological noise correction techniques, allowing detection of additional regions of task-related response and resting-state connectivity in highly vascularized regions such as occipital cortex. While these results serve to further rule out systemic physiological fluctuations as a significant source of apparent resting-state network connectivity, they also demonstrate that fluctuations in arterial CO(2) are one of the factors limiting sensitivity in task-based and resting-state fMRI, particularly in regions of high vascular density. This must be considered when comparing subject groups who might exhibit differences in respiratory physiology or breathing patterns.

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Human anterior prefrontal cortex encodes the 'what' and 'when' of future intentions.

Publication Date: 2012 May 15 PMID: 22418393
Authors: Momennejad, I. - Haynes, J. D.
Journal: Neuroimage

On a daily basis we form numerous intentions to perform specific actions. However, we often have to delay the execution of intended actions while engaging in other demanding activities. Previous research has shown that patterns of activity in human prefrontal cortex (PFC) can reveal our current intentions. However, two fundamental questions have remained unresolved: (a) how does the PFC encode information about future tasks while we are busy engaging in other activities, and (b) how does the PFC enable us to commence a stored task at the intended time? Here we investigate how the brain stores and retrieves future intentions during occupied delays, i.e. while a person is busy performing a different task. For this purpose, we conducted a neuroimaging study with a time-based prospective memory paradigm. Using multivariate pattern classification and fMRI we show that during an occupied delay, activity patterns in the anterior PFC encode the content of 'what' subjects intend to do next, and 'when' they intend to do it. Importantly, distinct anterior PFC regions store the 'what' and 'when' components of future intentions during occupied maintenance and self-initiated retrieval. These results show a role for anterior PFC activity patterns in storing future action plans and ensuring their timely retrieval.

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Hippocampal subfield volumes correlate with memory training benefit in subjective memory impairment.

Publication Date: 2012 May 15 PMID: 22414994
Authors: Engvig, A. - Fjell, A. M. - Westlye, L. T. - Skaane, N. V. - Sundseth, O. - Walhovd, K. B.
Journal: Neuroimage

Although some older adults experiencing memory problems have been shown to benefit from cognitive training, evidence regarding who will improve from this type of intervention is lacking. Automated hippocampal volumetry might be used to foresee treatment outcomes. We hypothesized that larger hippocampal volumes are associated with greater memory performance changes following training, and that effects are selectively related to specific hippocampal subfields. 19 memory clinic outpatients with subjective memory impairment (mean age=60.9years) underwent MRI-scanning and then followed an eight week training scheme aimed at improving verbal memory. We assessed verbal memory before and after training, and tested whether pretraining hippocampal volumes were related to memory improvements. To delineate regional specificity, we employed a new technique enabling automated volumetry of seven hippocampal subfields - including the cornu ammonis (CA) sectors and the dentate gyrus (DG). The results showed that larger hippocampal volumes before training were related to greater verbal recall improvements. Subfield volumetry revealed specific correlations between memory improvement and pretraining volumes of the left CA2/3 and CA4/DG. Depressive symptoms further gave a unique contribution in predicting gain of the intervention, independent of hippocampal volume. The results indicated that subjects with a stronger depressive symptom load benefited more from the training. A prediction model including baseline CA2/3-volume and depressive symptoms explained 42% of the variation in recall improvement. Our results are the first to suggest that hippocampal subfield volumetry is related to intervention outcomes in older adults experiencing memory problems. Also, previous studies have tended to exclude patients with concomitant depressive symptoms and memory complaints. The present results, however, strengthen the rationale and potential for cognitive intervention in these patients.

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Visual analytics of brain networks.

Publication Date: 2012 May 15 PMID: 22414991
Authors: Li, K. - Guo, L. - Faraco, C. - Zhu, D. - Chen, H. - Yuan, Y. - Lv, J. - Deng, F. - Jiang, X. - Zhang, T. - Hu, X. - Zhang, D. - Miller, L. S. - Liu, T.
Journal: Neuroimage

Identification of regions of interest (ROIs) is a fundamental issue in brain network construction and analysis. Recent studies demonstrate that multimodal neuroimaging approaches and joint analysis strategies are crucial for accurate, reliable and individualized identification of brain ROIs. In this paper, we present a novel approach of visual analytics and its open-source software for ROI definition and brain network construction. By combining neuroscience knowledge and computational intelligence capabilities, visual analytics can generate accurate, reliable and individualized ROIs for brain networks via joint modeling of multimodal neuroimaging data and an intuitive and real-time visual analytics interface. Furthermore, it can be used as a functional ROI optimization and prediction solution when fMRI data is unavailable or inadequate. We have applied this approach to an operation span working memory fMRI/DTI dataset, a schizophrenia DTI/resting state fMRI (R-fMRI) dataset, and a mild cognitive impairment DTI/R-fMRI dataset, in order to demonstrate the effectiveness of visual analytics. Our experimental results are encouraging.

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Impact of hemodynamic effects on diffusion-weighted fMRI signals.

Publication Date: 2012 May 15 PMID: 22406501
Authors: Rudrapatna, U. S. - van der Toorn, A. - van Meer, M. P. - Dijkhuizen, R. M.
Journal: Neuroimage

In some recent studies, diffusion weighted functional MRI has been proposed to provide contrast immune to vascular changes. Increases in relative signal change during neuronal activation observed under increasing diffusion weighting support the possible diffusion based origin of this contrast. A recent diffusion tensor imaging (DTI) study has also reported the use of Fractional Anisotropy (FA) to track activation in white matter. In this study we aimed to establish if relatively high diffusion weighting (b=1200 and 1800s/mm(2)) eliminates the strong vascular influences brought about by 100% O(2) and carbogen (95%O(2)+5% CO(2)) induced vascular challenges in gray matter (GM) and white matter (WM) of rat brain. We also aimed to characterize the influences of these vascular changes on FA, both in GM and in WM. Our study endorses previous reports that even relatively heavily diffusion weighted data can be significantly influenced by hemodynamic changes. However, this was not only observed in GM, but also in WM. Moreover, our study demonstrates that the estimator used to calculate the relative changes should be carefully chosen in order to avoid biases at low signal-to-noise ratios (SNRs) which accompany increasing diffusion weighting. With the use of robust estimators, we found no increases in relative change with increasing b-value during both vascular challenges. Our data also demonstrate that FA can be significantly influenced by hemodynamics, both in GM and in WM. The observed influence of diffusion weighting direction on relative signal change in GM was shown to be associated with structural differences among various regions. If diffusion based functional contrasts immune to hemodynamics do exist, our results highlight the difficulty in discerning those diffusion changes from accompanying vascular changes.

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Understanding the neural mechanisms involved in sensory control of voice production.

Publication Date: 2012 May 15 PMID: 22406500
Authors: Parkinson, A. L. - Flagmeier, S. G. - Manes, J. L. - Larson, C. R. - Rogers, B. - Robin, D. A.
Journal: Neuroimage

Auditory feedback is important for the control of voice fundamental frequency (F0). In the present study we used neuroimaging to identify regions of the brain responsible for sensory control of the voice. We used a pitch-shift paradigm where subjects respond to an alteration, or shift, of voice pitch auditory feedback with a reflexive change in F0. To determine the neural substrates involved in these audio-vocal responses, subjects underwent fMRI scanning while vocalizing with or without pitch-shifted feedback. The comparison of shifted and unshifted vocalization revealed activation bilaterally in the superior temporal gyrus (STG) in response to the pitch shifted feedback. We hypothesize that the STG activity is related to error detection by auditory error cells located in the superior temporal cortex and efference copy mechanisms whereby this region is responsible for the coding of a mismatch between actual and predicted voice F0.

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From N400 to N300: Variations in the timing of semantic processing with repetition.

Publication Date: 2012 May 15 PMID: 22406358
Authors: Renoult, L. - Wang, X. - Calcagno, V. - Prevost, M. - Debruille, J. B.
Journal: Neuroimage

The present study aimed to explore the variations of semantic processing according to the number of target words (i.e., 4, 12 and 24) and according to the number of repetitions (i.e, 1 to 15). The number of targets had no impact on the N400 brain potential, the index of semantic processing, nor on the late positive component (LPC), an index of episodic encoding and retrieval. Analyses of the effects of the number of repetitions showed that the duration of semantic processes - assessed by measuring N400 latency - was linearly shortened along repetitions while their extent - as indexed by N400 amplitude - remained constant after the second presentation. In contrast, the extent of episodic processes - as indexed by LPC amplitude - was found to increase linearly with repetition. By showing that N400 latency may be much less stable than previously thought, these results bring new constraints on the functional correlates of this key stage in the processing of semantic information. They also suggest that semantic processes can be studied at high repetition rates whatever the number of target stimuli. Finally, our findings show that each episode of prior presentation has an impact on the late processing of a stimulus despite the absence of an explicit memory task.

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The neural correlates of subjective pleasantness.

Publication Date: 2012 May 15 PMID: 22406357
Authors: Kuhn, S. - Gallinat, J.
Journal: Neuroimage

Processing of subjective pleasantness is essential in daily life decision making, particularly in the context of cognitive and environmental factors. Pleasure is mediated by a neural network and this network has been suggested to be the biological basis of pleasure including a whole range of different modalities and domains of pleasantness. This quantitative meta-analysis of brain imaging data focuses on studies 1) based on correlations between self-reported judgements of pleasantness and brain regions and investigates whether 2) immediate (during scanning) versus subsequent judgements (after scanning) differ in brain activity. We investigated concurrence across 40 studies reporting brain regions correlated with self-reported judgements of subjective pleasantness (attractiveness, liking or beauty) by means of activation likelihood estimation (ALE). Positive correlates of subjective pleasantness were found in mOFC, ventromedial prefrontal cortex, left ventral striatum, pregenual cortex, right cerebellum, left thalamus and the mid cingulate cortex. Negative correlates were found in left precentral gyrus, right cerebellum and right inferior frontal gyrus. A comparison of studies with subjective pleasantness judgement during or after scanning revealed no significant differences in brain activation. We conclude that subjective pleasantness judgements are directly related to brain regions that have been described as part of the reward circuitry (mOFC, ventral striatum). The results suggest that the evaluation of likability or pleasure is an automatic process and that it is neither elicited nor enhanced by instructions to report the outcome of these judgements.

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Impact of L-DOPA treatment on regional cerebral blood flow and metabolism in the basal ganglia in a rat model of Parkinson's disease.

Publication Date: 2012 May 15 PMID: 22406356
Authors: Ohlin, K. E. - Sebastianutto, I. - Adkins, C. E. - Lundblad, C. - Lockman, P. R. - Cenci, M. A.
Journal: Neuroimage

Large increases in regional cerebral blood flow (rCBF) have been measured in patients with Parkinson's disease (PD) following the administration of L-DOPA, but the underlying mechanisms have remained unknown. In this study, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions were used to compare patterns of rCBF and regional cerebral glucose utilisation (rCGU) in chronically L-DOPA-treated subjects following a final injection of L-DOPA or saline. The same animal model was used to the leakage of a blood-brain barrier (BBB) tracer molecule at 60min vs. 24h following the last L-DOPA injection of a chronic treatment. All the parameters under investigation were examined with brain autoradiography following intravenous injections of specific radiotracers in awake animals ([14C]-iodoantipyrine for rCBF, [14C]-2-deoxyglucose for rCGU, and [14C]-alpha-aminoisobutyric acid for BBB leakage). Significant changes in rCBF and rCGU on the side ipsilateral to the 6-OHDA lesion relative to the non-lesioned side were seen at 60min ("ON") but not 24h ("OFF") following L-DOPA administration. These changes were not seen in sham-operated rats. In the output nuclei of the basal ganglia (the entopeduncular nucleus and the substantia nigra pars reticulata) both rCBF and rCGU were elevated both in acutely L-DOPA-treated rats and chronically L-DOPA-treated rats displaying dyskinesia, but did not change significantly in chronically L-DOPA-treated non-dyskinetic cases. Acutely and chronically L-DOPA-treated rats with dyskinesia exhibited increases in rCBF "ON L-DOPA" also in the motor cortex, the striatum, and the globus pallidus, but the corresponding changes in rCGU did not show the same direction, magnitude, and/or relative group differences. The uptake of a BBB tracer (studied in the striatum and the substantia nigra reticulata in chronically L-DOPA treated rats) was significantly higher ON vs. OFF L-DOPA. The present results are the first to show that the administration of L-DOPA is followed by transient and robust increases in rCBF in the dopamine-denervated basal ganglia. This effect occurs already upon acute L-DOPA treatment and persists upon repeated drug administration in animals that develop dyskinesia. Increases in rCBF ON L-DOPA are not necessarily accompanied by enhanced glucose utilisation in the affected regions, pointing to altered mechanisms of neurovascular coupling. Finally, our results show that increases in rCBF ON L-DOPA may be accompanied by BBB hyperpermeability in the most affected regions.

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Correlates of perceptual awareness in human primary auditory cortex revealed by an informational masking experiment.

Publication Date: 2012 May 15 PMID: 22406354
Authors: Wiegand, K. - Gutschalk, A.
Journal: Neuroimage

The presence of an auditory event may remain undetected in crowded environments, even when it is well above the sensory threshold. This effect, commonly known as informational masking, allows for isolating neural activity related to perceptual awareness, by comparing repetitions of the same physical stimulus where the target is either detected or not. Evidence from magnetoencephalography (MEG) suggests that auditory-cortex activity in the latency range 50-250ms is closely coupled with perceptual awareness. Here, BOLD fMRI and MEG were combined to investigate at which stage in the auditory cortex neural correlates of conscious auditory perception can be observed. Participants were asked to indicate the perception of a regularly repeating target tone, embedded within a random multi-tone masking background. Results revealed widespread activation within the auditory cortex for detected target tones, which was delayed but otherwise similar to the activation of an unmasked control stimulus. The contrast of detected versus undetected targets revealed activity confined to medial Heschl's gyrus, where the primary auditory cortex is located. These results suggest that activity related to conscious perception involves the primary auditory cortex and is not restricted to activity in secondary areas.

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A clustering-based method to detect functional connectivity differences.

Publication Date: 2012 May 15 PMID: 22405733
Authors: Chen, G. - Ward, B. D. - Xie, C. - Li, W. - Chen, G. - Goveas, J. S. - Antuono, P. G. - Li, S. J.
Journal: Neuroimage

Recently, resting-state functional magnetic resonance imaging (R-fMRI) has emerged as a powerful tool for investigating functional brain organization changes in a variety of neurological and psychiatric disorders. However, the current techniques may need further development to better define the reference brain networks for quantifying the functional connectivity differences between normal and diseased subject groups. In this study, we introduced a new clustering-based method that can clearly define the reference clusters. By employing group difference information to guide the clustering, the voxels within the reference clusters will have homogeneous functional connectivity changes above predefined levels. This method identified functional clusters that were significantly different between the amnestic mild cognitively impaired (aMCI) and age-matched cognitively normal (CN) subjects. The results indicated that the distribution of the clusters and their functionally disconnected regions resembled the altered memory network regions previously identified in task fMRI studies. In conclusion, the new clustering method provides an advanced approach for studying functional brain organization changes associated with brain diseases.

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Nonverbal sound processing in semantic dementia: A functional MRI study.

Publication Date: 2012 May 15 PMID: 22405732
Authors: Goll, J. C. - Ridgway, G. R. - Crutch, S. J. - Theunissen, F. E. - Warren, J. D.
Journal: Neuroimage

Semantic dementia (SD) is a unique neurodegenerative syndrome accompanied by relatively selective loss of the meaning of objects and concepts. The brain mechanisms that underpin the syndrome have not been defined: a better understanding of these mechanisms would inform our understanding of both the organisation of the human semantic system and its vulnerability to neurodegenerative disease. In this fMRI study, we investigated brain correlates of sensory object processing in nine patients with SD compared with healthy control subjects, using the paradigm of nonverbal sound. Compared with healthy controls, patients with SD showed differential activation of cortical areas surrounding the superior temporal sulcus, both for perceptual processing of spectrotemporally complex but meaningless sounds and for semantic processing of environmental sound category (animal sounds versus tool sounds). Our findings suggest that defective processing of sound objects in SD spans pre-semantic perceptual processing and semantic category formation. This disease model illustrates that antero-lateral temporal cortical mechanisms are critical for representing and differentiating sound categories. The breakdown of these mechanisms constitutes a network-level functional signature of this neurodegenerative disease.

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Lowered frequency and impaired modulation of gamma band oscillations in a bimodal attention task are associated with reduced critical flicker frequency.

Publication Date: 2012 May 15 PMID: 22405731
Authors: Kahlbrock, N. - Butz, M. - May, E. S. - Brenner, M. - Kircheis, G. - Haussinger, D. - Schnitzler, A.
Journal: Neuroimage

Visual attention is associated with occipital gamma band activity. While gamma band power can be modulated by attention, the frequency of gamma band activity is known to decrease with age. The present study tested the hypothesis that reduced visual attention is associated with a change in induced gamma band activity. To this end, 26 patients with liver cirrhosis and 8 healthy controls were tested. A subset of patients showed symptoms of hepatic encephalopathy (HE), a frequent neuropsychiatric complication in liver disease, which comprises a gradual increase of cognitive dysfunction including attention deficits. All participants completed a behavioral task requiring shifts of attention between simultaneously presented visual and auditory stimuli. Brain activity was recorded using magnetoencephalography (MEG). The individual critical flicker frequency (CFF) was assessed as it is known to reliably reflect the severity of HE. Results showed correlations of behavioral data and HE severity, as indexed by CFF. Individual visual gamma band peak frequencies correlated positively with the CFF (r=0.41). Only participants with normal, but not with pathological CFF values showed a modulation of gamma band power with attention. The present results suggest that CFF and attentional performance are related. Moreover, a tight relation between the CFF and occipital gamma band activity both in frequency and power is shown. Thus, the present study provides evidence that a reduced CFF in HE, a disease associated with attention deficits, is closely linked to a slowing of gamma band activity and impaired modulation of gamma band power in a bimodal attention task.

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Effects of image distortions originating from susceptibility variations and concomitant fields on diffusion MRI tractography results.

Publication Date: 2012 May 15 PMID: 22401760
Authors: Irfanoglu, M. O. - Walker, L. - Sarlls, J. - Marenco, S. - Pierpaoli, C.
Journal: Neuroimage

In this work we investigate the effects of echo planar imaging (EPI) distortions on diffusion tensor imaging (DTI) based fiber tractography results. We propose a simple experimental framework that would enable assessing the effects of EPI distortions on the accuracy and reproducibility of fiber tractography from a pilot study on a few subjects. We compare trajectories computed from two diffusion datasets collected on each subject that are identical except for the orientation of phase encode direction, either right-left (RL) or anterior-posterior (AP). We define metrics to assess potential discrepancies between RL and AP trajectories in association, commissural, and projection pathways. Results from measurements on a 3Tesla clinical scanner indicated that the effects of EPI distortions on computed fiber trajectories are statistically significant and large in magnitude, potentially leading to erroneous inferences about brain connectivity. The correction of EPI distortion using an image-based registration approach showed a significant improvement in tract consistency and accuracy. Although obtained in the context of a DTI experiment, our findings are generally applicable to all EPI-based diffusion MRI tractography investigations, including high angular resolution (HARDI) methods. On the basis of our findings, we recommend adding an EPI distortion correction step to the diffusion MRI processing pipeline if the output is to be used for fiber tractography.

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Contributions of dynamic venous blood volume versus oxygenation level changes to BOLD fMRI.

Publication Date: 2012 May 1 PMID: 22401759
Authors: Zong, X. - Kim, T. - Kim, S. G.
Journal: Neuroimage

Blood-oxygenation-level-dependent (BOLD) fMRI has contributions from venous oxygenation and venous cerebral blood volume (CBV) changes. To examine the relative contribution of venous CBV change (DeltaCBV(v)) to BOLD fMRI, BOLD and arterial CBV changes (DeltaCBV(a)) to a 40-s forepaw stimulation in six alpha-chloralose anesthetized rats were measured using a magnetization transfer-varied fMRI technique, while total CBV change (DeltaCBV(t)) was measured with injection of iron oxide nanoparticles. DeltaCBV(v) was obtained by subtracting DeltaCBV(a) from DeltaCBV(t). We observed a fast DeltaCBV(a) response with a time constant of 2.9 +/- 2.3s and a slower DeltaCBV(v) response with a time constant of 13.5 +/- 5.7s and an onset delay of 6.1 +/- 3.3s. These results are consistent with earlier studies under different anesthesia and stimulus, supporting that fast CBV(a) and slow CBV(v) responses are generalizable. Assuming the observed post-stimulus BOLD undershoot is at least partly explained by the DeltaCBV(v) contribution, the relative contribution of the DeltaCBV(v)- and oxygenation-change-related components to the BOLD response was estimated. The relative DeltaCBV(v) contribution increases with time during stimulation; whereby it is <0.14 during initial 10s and reaches a maximum possible value of ~0.45 relative to the oxygenation contribution during the 30-40s period after stimulus onset. Our data indicates that the contribution of venous oxygenation change to BOLD fMRI is dominant for short stimulations.

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Investigation of fMRI neurofeedback of differential primary motor cortex activity using kinesthetic motor imagery.

Publication Date: 2012 May 15 PMID: 22401758
Authors: Chiew, M. - Laconte, S. M. - Graham, S. J.
Journal: Neuroimage

Functional MRI neurofeedback (fMRI NF) is an emerging technique that trains subjects to regulate their brain activity while they manipulate sensory stimulus representations of fMRI signals in "real-time". Here we report an fMRI NF study of brain activity associated with kinesthetic motor imagery (kMI), analyzed using partial least squares (PLS), a multivariate analysis technique. Thirteen healthy young adult subjects performed kMI involving each hand separately, with NF training targeting regions of interest (ROIs) in the left and right primary motor cortex (M1). Throughout, subjects attempted to maximize a laterality index (LI) of brain activity-the difference in activity between the contralateral ROI (relative to the hand involved in kMI) and the ipsilateral M1 ROI-while receiving real-time updates on a visual display. Six of 13 subjects were successful in increasing the LI value, whereas the other 7 were not successful and performed similarly to 5 control subjects who received sham NF training. Ability to suppress activity in the ipsilateral M1 ROI was the primary driver of successful NF performance. Multiple PLS analyses depicted activated networks of brain regions involved with imagery, self-awareness, and feedback processing, and additionally showed that activation of the task positive network was correlated with task performance. These results indicate that fMRI NF of kMI is capable of modulating brain activity in primary motor regions in a subset of the population. In the future, such methods may be useful in the development of NF training methods for enhancing motor rehabilitation following stroke.

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Quantifying cerebellar atrophy in multiple system atrophy of the cerebellar type (MSA-C) using three-dimensional gyrification index analysis.

Publication Date: 2012 May 15 PMID: 22401757
Authors: Wu, Y. T. - Shyu, K. K. - Jao, C. W. - Liao, Y. L. - Wang, T. Y. - Wu, H. M. - Wang, P. S. - Soong, B. W.
Journal: Neuroimage

Multiple system atrophy of the cerebellar type (MSA-C) is a degenerative neurological disease of the central nervous system. This study employed a method named, "surface-based three-dimensional gyrification index" (3D-GI) to quantify morphological changes in normal cerebellum (including brainstem) and atrophied cerebellum, in patients with MSA-C. We assessed whether 3D-GI can exclude gender and age differences to quantify cerebellum and brainstem atrophy more accurately. Sixteen healthy subjects and 16 MSA-C patients participated in this study. We compared 3D-GI values and volumes in the cerebellum, based on T1-weighted MR images. We also compared the images of reconstructed 3D cerebellum gray matter (3D-CBGM) and cerebellum white matter (3D-CBWM) to detect the atrophied cerebellar region in MSA-C patients. The 3D-GI values were in a stable range with small variances, exhibiting no gender effect and no age-related shrinkage. Significantly lower 3D-GI values were exhibited in both CBGM and CBWM of the MSA-C patients compared with healthy subjects, even in the early phases of the disease. Decreases in 3D-GI values indicated the degeneration of the cerebellar folding structure, exactly reflecting the morphological changes in cerebellum. The 3D-GI method based on CBGM resulted in superior discriminative accuracy compared with the CBGM volumetric method. Using the two-dimensional 3D-GI values, the K-means classifier can evidently discriminate the MSA-C patients from healthy subjects.

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An algorithmic method for functionally defining regions of interest in the ventral visual pathway.

Publication Date: 2012 May 1 PMID: 22398396
Authors: Julian, J. B. - Fedorenko, E. - Webster, J. - Kanwisher, N.
Journal: Neuroimage

In a widely used functional magnetic resonance imaging (fMRI) data analysis method, functional regions of interest (fROIs) are handpicked in each participant using macroanatomic landmarks as guides, and the response of these regions to new conditions is then measured. A key limitation of this standard handpicked fROI method is the subjectivity of decisions about which clusters of activated voxels should be treated as the particular fROI in question in each subject. Here we apply the Group-Constrained Subject-Specific (GSS) method for defining fROIs, recently developed for identifying language fROIs (Fedorenko et al., 2010), to algorithmically identify fourteen well-studied category-selective regions of the ventral visual pathway (Kanwisher, 2010). We show that this method retains the benefit of defining fROIs in individual subjects without the subjectivity inherent in the traditional handpicked fROI approach. The tools necessary for using this method are available on our website (http://web.mit.edu/bcs/nklab/GSS.shtml).

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Enhancement of temporal resolution and BOLD sensitivity in real-time fMRI using multi-slab echo-volumar imaging.

Publication Date: 2012 May 15 PMID: 22398395
Authors: Posse, S. - Ackley, E. - Mutihac, R. - Rick, J. - Shane, M. - Murray-Krezan, C. - Zaitsev, M. - Speck, O.
Journal: Neuroimage

In this study, a new approach to high-speed fMRI using multi-slab echo-volumar imaging (EVI) is developed that minimizes geometrical image distortion and spatial blurring, and enables nonaliased sampling of physiological signal fluctuation to increase BOLD sensitivity compared to conventional echo-planar imaging (EPI). Real-time fMRI using whole brain 4-slab EVI with 286ms temporal resolution (4mm isotropic voxel size) and partial brain 2-slab EVI with 136ms temporal resolution (4x4x6mm(3) voxel size) was performed on a clinical 3 Tesla MRI scanner equipped with 12-channel head coil. Four-slab EVI of visual and motor tasks significantly increased mean (visual: 96%, motor: 66%) and maximum t-score (visual: 263%, motor: 124%) and mean (visual: 59%, motor: 131%) and maximum (visual: 29%, motor: 67%) BOLD signal amplitude compared with EPI. Time domain moving average filtering (2s width) to suppress physiological noise from cardiac and respiratory fluctuations further improved mean (visual: 196%, motor: 140%) and maximum (visual: 384%, motor: 200%) t-scores and increased extents of activation (visual: 73%, motor: 70%) compared to EPI. Similar sensitivity enhancement, which is attributed to high sampling rate at only moderately reduced temporal signal-to-noise ratio (mean: -52%) and longer sampling of the BOLD effect in the echo-time domain compared to EPI, was measured in auditory cortex. Two-slab EVI further improved temporal resolution for measuring task-related activation and enabled mapping of five major resting state networks (RSNs) in individual subjects in 5min scans. The bilateral sensorimotor, the default mode and the occipital RSNs were detectable in time frames as short as 75s. In conclusion, the high sampling rate of real-time multi-slab EVI significantly improves sensitivity for studying the temporal dynamics of hemodynamic responses and for characterizing functional networks at high field strength in short measurement times.

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Structural connectivity allows for multi-threading during rest: the structure of the cortex leads to efficient alternation between resting state exploratory behavior and default mode processing.

Publication Date: 2012 May 1 PMID: 22394674
Authors: Senden, M. - Goebel, R. - Deco, G.
Journal: Neuroimage

Despite the absence of stimulation or task conditions the cortex exhibits highly structured spatio-temporal activity patterns. These patterns are known as resting state networks (RSNs) and emerge as low-frequency fluctuations (<0.1 Hz) observed in the fMRI signal of human subjects during rest. We are interested in the relationship between structural connectivity of the cortex and the fluctuations exhibited during resting conditions. We are especially interested in the effect of degree of connectivity on resting state dynamics as the default mode network (DMN) is highly connected. We find in experimental resting fMRI data that the DMN is the functional network that is most frequently active and for the longest time. In large-scale computational simulations of the cortex based on the corresponding underlying DTI/DSI based neuroanatomical connectivity matrix, we additionally find a strong correlation between the mean degree of functional networks and the proportion of time they are active. By artificially modifying different types of neuroanatomical connectivity matrices in the model, we were able to demonstrate that only models based on structural connectivity containing hubs give rise to this relationship. We conclude that, during rest, the cortex alternates efficiently between explorations of its externally oriented functional repertoire and internally oriented processing as a consequence of the DMN's high degree of connectivity.

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Confounding of norm-based and adaptation effects in brain responses.

Publication Date: 2012 May 1 PMID: 22394673
Authors: Kahn, D. A. - Aguirre, G. K.
Journal: Neuroimage

Separate neuroscience experiments have examined two properties of neural coding for perceptual stimuli. Adaptation studies seek a graded recovery from neural adaptation with ever greater dissimilarity between pairs of stimuli. Studies of prototype effects test for a larger absolute response to a stimulus which is distant from the center of a stimulus space. While intellectually distinct, these effects are confounded in measurement in standard neuroscience paradigms and can be mistaken for one another. Stimuli which are more distinctive are less subject to adaptation from perceptual neighbors. Therefore, a putative prototype effect may simply result from greater adaptation of prototypical stimuli by other stimuli in the experiment. Conversely, stimulus pairs which are the most perceptually distant from one another, and therefore expected to show the greatest recovery from adaptation, disproportionately draw from the extremes of the stimulus space. Thus, an apparent neural similarity effect may be created by an underlying prototype representation. We simulate BOLD fMRI results driven by each possible effect and demonstrate spurious results in support of the complementary effect. We then present an example fMRI experiment that demonstrates the confound and how it may be minimized. Finally, we discuss the implications of this intrinsic confound for studies of perceptual representation, neural coding, and category learning.

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Meanfield modeling of propofol-induced changes in spontaneous EEG rhythms.

Publication Date: 2012 May 1 PMID: 22394672
Authors: Hindriks, R. - van Putten, M. J.
Journal: Neuroimage

During the maintenance period of propofol-induced general anesthesia, specific changes in spontaneous EEG rhythms can be observed. These comprise increased delta and theta power and the emergence of alpha oscillations over frontal regions. In this study we use a meanfield model of the thalamo-cortical system to reproduce these changes and to elucidate the underlying mechanisms. The model is able to reproduce the most dominant changes in the EEG and suggests that they are caused by the amplification of resonances within the thalamo-cortical system. Specifically, while observed increases in delta and alpha power are reflections of amplified resonances in the respective frequency bands, increases in theta power are caused indirectly by spectral power leakage from delta and alpha bands. The model suggests that these changes are brought about through increased inhibition within local cortical interneuron circuits. These results are encouraging and motivate more extensive use of neural meanfield models in elucidating the physiological mechanisms underlying the effects of pharmacological agents on macroscopic brain dynamics.

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Decision-making under risk: a graph-based network analysis using functional MRI.

Publication Date: 2012 May 1 PMID: 22387471
Authors: Minati, L. - Grisoli, M. - Seth, A. K. - Critchley, H. D.
Journal: Neuroimage

Adaptive behavior requires choosing effectively between options involving risks and potential rewards. Existing studies implicate lateral and medial prefrontal areas, striatum, insula, amygdala and parietal regions in specific aspects of decision-making. However, limited attention is given to how brain networks encode economic parameters in patterns of inter-regional interactions. Here, healthy participants underwent functional MRI while evaluating "mixed" gambles presenting potential gains, losses and associated outcome probabilities. Connectivity graphs were constructed from analyses of psychophysiological interactions across a comprehensive atlas of brain regions. Expected value correlated positively with activity within medial prefrontal and occipital cortices, and modulated effective connectivity across a network that extended substantially beyond these nodes. Value-sensitive effective connections were found to be arranged as a unitary, small world network in which medial and anterior-lateral prefrontal areas featured as hubs, characterized by dense connectivity and high shortest-path centrality. Further analyses revealed that the observed effective connectivity effects were more pertinent to dichotomous gain/loss comparisons than to continuous value determination. Factoring expected value into its constituent components, potential loss modulated connectivity across a subset of the value-sensitive network, whereas potential gain and outcome probability were not significantly embodied in functional interactions. Regional response non-linearity was excluded as an artifactual basis to the observed effects, and directionality inferences were confirmed by comparison of dynamic causal models. Our findings extend current literature demonstrating that the representation of value is dependent on distributed processing taking across a widespread network which feeds information into a limited set of integrative prefrontal nodes. This study also has more general paradigmatic implications for neuroeconomics, demonstrating the value of explicit modeling of inter-regional interactions for understanding the neural substrates of decisional processes.

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Multi-stage segmentation of white matter hyperintensity, cortical and lacunar infarcts.

Publication Date: 2012 May 1 PMID: 22387175
Authors: Wang, Y. - Catindig, J. A. - Hilal, S. - Soon, H. W. - Ting, E. - Wong, T. Y. - Venketasubramanian, N. - Chen, C. - Qiu, A.
Journal: Neuroimage

Cerebral abnormalities such as white matter hyperintensity (WMH), cortical infarct (CI), and lacunar infarct (LI) are of clinical importance and frequently present in patients with stroke and dementia. Up to date, there are limited algorithms available to automatically delineate these cerebral abnormalities partially due to their complex appearance in MR images. In this paper, we describe an automated multi-stage segmentation approach for labeling the WMH, CI, and LI using multi-modal MR images. We first automatically segment brain tissues (white matter, gray matter, and CSF) based on the T1-weighted image and then identify hyperintense voxels based on the fluid attenuated inversion recovery (FLAIR) image. We finally label the WMH, CI, and LI based on the T1-weighted, T2-weighted, and FLAIR images. The segmentation accuracy is evaluated using a community-based sample of 272 old adults. Our results show that the automated segmentation of the WMH, CI, and LI is comparable with manual labeling in terms of spatial location, volume, and the number of lacunes. Additionally, the WMH volume is highly correlated with the visual grading score based on the Age-Related White Matter Changes (ARWMC) protocol. The evaluations against the manual labeling and ARWMC visual grading suggest that our algorithm provides reasonable segmentation accuracy for the WMH, CI, and LI.

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Catechol-O-methyltransferase gene variation: impact on amygdala response to aversive stimuli.

Publication Date: 2012 May 1 PMID: 22387174
Authors: Domschke, K. - Baune, B. T. - Havlik, L. - Stuhrmann, A. - Suslow, T. - Kugel, H. - Zwanzger, P. - Grotegerd, D. - Sehlmeyer, C. - Arolt, V. - Dannlowski, U.
Journal: Neuroimage

The functional catechol-O-methyltransferase (COMT) val158met polymorphism has been found to be associated with anxiety disorders and depression as well as with neural correlates of emotional processing, with, however, contradictory results. Thus, the aim of the present study was to re-evaluate the impact of the COMT val158met variant on neural activation correlates of emotional face processing in a sample of healthy probands. In 85 healthy subjects genotyped for the COMT val158met polymorphism, amygdala responses were assessed by means of fMRI. Participants were presented with anger- and fear-relevant faces in a robust emotion-processing paradigm. For exploratory reasons, a supplementary whole-brain analysis of the allele-dose model and a gender-stratified analysis were conducted. The COMT 158val allele showed an allele-dose effect on increased predominantly left-sided amygdala activity in response to fearful/angry facial stimuli (p(uncorrected)=.00004). This effect was independent from the distribution of the frequently studied 5-HTTLPR polymorphism for which a linear effect of S-alleles on amygdala responsiveness was replicated. The influence of COMT 158val alleles was only discerned in the female subgroup of probands. The whole-brain analysis suggested associations of the COMT 158val allele with increased activity in areas of the ventral visual stream and the lateral prefrontal cortex. The present results provide further support for a-potentially female-specific-role of the COMT val158met polymorphism in the genetic and neural underpinnings of anxiety- and depression-related intermediate phenotypes and may aid in further clarifying the differential role of COMT genotype driven dopaminergic tonus in the processing of emotionally salient stimuli.

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Quantitative evaluation of white matter tract DTI parameter changes in gliomas using nonlinear registration.

Publication Date: 2012 May 1 PMID: 22387173
Authors: Miller, P. - Coope, D. - Thompson, G. - Jackson, A. - Herholz, K.
Journal: Neuroimage

Diffusion tensor imaging (DTI) has been used extensively to investigate white matter architecture in the brain. In the context of neurological disease, quantification of DTI data sets enables objective characterisation of the associated pathological changes. The aim of this study is to propose a method of evaluating DTI parameter changes in gliomas in the internal capsule using nonlinear registration to delineate the white matter and enable quantitative assessment of DTI derived parameters. 20 patients selected pre-operatively with probable grade 2 or grade 3 glioma on structural MRI along with ten normal volunteers were included in this study. DTI fractional anisotropy (FA) maps were used to define a common segmented FA skeleton that was projected back onto the original individual FA maps. Objective segment classification as normal or abnormal was achieved by comparison to prediction intervals of FA and mean diffusivity (MD) defined in normal subjects. The internal capsules of each patient were segmented into 10 regions of interest (ROI) with 20 and 16 segments across the group having significantly increased or decreased FA and MD values respectively. Seven glioma patients had abnormal DTI parameters in the internal capsule. We show that the classification of tract segments was consistent with disruption, oedema or compression. The results suggest that this method could be used to detect changes in eloquent white matter tracts in individual patients.

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Stimulus repetition probability effects on repetition suppression are position invariant for faces.

Publication Date: 2012 May 1 PMID: 22387172
Authors: Kovacs, G. - Iffland, L. - Vidnyanszky, Z. - Greenlee, M. W.
Journal: Neuroimage

It has been shown that the probability of face repetitions influences the magnitude of repetition-related response reductions (Summerfield et al., 2008), implying that perceptual expectations affect adaptation and repetition suppression processes in the human central nervous system. An unresolved question is whether probability effects are specific for the retinal position of the stimuli or affect stimulus processing globally, throughout the visual field. To address this question we tested whether face repetition probability affects fMRI adaptation (fMRIa) when the repeated stimuli are presented on the same retinal position, overlapping each other or when they are presented in opposite hemifields. Subjects were exposed to either two identical (repeated trial, RT) or two different (alternating trial, AT) face stimuli. Both types of trials were presented either in blocks consisting of 75% (repeated block, RB) or 25% (alternating block, AB) of RTs. We found that repetition probability influences fMRIa equally for overlapping and nonoverlapping arrangements: the signal reduction after RT was more pronounced in RB than in AB for both spatial arrangements of stimulus-pairs. This effect was present in bilateral fusiform and occipital face areas, as well as in the lateral occipital cortex. Our results support the role of stimulus repetition probability in determining fMRIa and shows that the effect is invariant to the retinal position of stimuli.

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Longitudinal change detection in diffusion MRI using multivariate statistical testing on tensors.

Publication Date: 2012 May 1 PMID: 22387171
Authors: Grigis, A. - Noblet, V. - Heitz, F. - Blanc, F. - de Seze, J. - Kremer, S. - Rumbach, L. - Armspach, J. P.
Journal: Neuroimage

This paper presents a longitudinal change detection framework for detecting relevant modifications in diffusion MRI, with application to neuromyelitis optica (NMO) and multiple sclerosis (MS). The core problem is to identify image regions that are significantly different between two scans. The proposed method is based on multivariate statistical testing which was initially introduced for tensor population comparison. We use this method in the context of longitudinal change detection by considering several strategies to build sets of tensors characterizing the variability of each voxel. These strategies make use of the variability existing in the diffusion weighted images (thanks to a bootstrap procedure), or in the spatial neighborhood of the considered voxel, or a combination of both. Results on synthetic evolutions and on real data are presented. Interestingly, experiments on NMO patients highlight the ability of the proposed approach to detect changes in the normal-appearing white matter (according to conventional MRI) that are related with physical status outcome. Experiments on MS patients highlight the ability of the proposed approach to detect changes in evolving and non-evolving lesions (according to conventional MRI). These findings might open promising prospects for the follow-up of NMO and MS pathologies.

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Across-study and within-subject functional connectivity of a right temporo-parietal junction subregion involved in stimulus-context integration.

Publication Date: 2012 May 1 PMID: 22387170
Authors: Jakobs, O. - Langner, R. - Caspers, S. - Roski, C. - Cieslik, E. C. - Zilles, K. - Laird, A. R. - Fox, P. T. - Eickhoff, S. B.
Journal: Neuroimage

Bidirectional integration between sensory stimuli and contextual framing is fundamental to action control. Stimuli may entail context-dependent actions, while temporal or spatial characteristics of a stimulus train may establish a contextual framework for upcoming stimuli. Here we aimed at identifying core areas for stimulus-context integration and delineated their functional connectivity (FC) using meta-analytic connectivity modeling (MACM) and analysis of resting-state networks. In a multi-study conjunction, consistently increased activity under higher demands on stimulus-context integration was predominantly found in the right temporo-parietal junction (TPJ), which represented the largest cluster of overlap and was thus used as the seed for the FC analyses. The conjunction between task-dependent (MACM) and task-free (resting state) FC of the right TPJ revealed a shared network comprising bilaterally inferior parietal and frontal cortices, anterior insula, premotor cortex, putamen and cerebellum, i.e., a 'ventral' action/attention network. Stronger task-dependent (vs. task-free) connectivity was observed with the pre-SMA, dorsal premotor cortex, intraparietal sulcus, basal ganglia and primary sensori motor cortex, while stronger resting-state (vs. task-dependent) connectivity was found with the dorsolateral prefrontal and medial parietal cortex. Our data provide strong evidence that the right TPJ may represent a key region for the integration of sensory stimuli and contextual frames in action control. Task-dependent associations with regions related to stimulus processing and motor responses indicate that the right TPJ may integrate 'collaterals' of sensory processing and apply (ensuing) contextual frames, most likely via modulation of preparatory loops. Given the pattern of resting-state connectivity, internal states and goal representations may provide the substrates for the contextual integration within the TPJ in the absence of a specific task.

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Spectrotemporal processing drives fast access to memory traces for spoken words.

Publication Date: 2012 May 1 PMID: 22387169
Authors: Tavano, A. - Grimm, S. - Costa-Faidella, J. - Slabu, L. - Schroger, E. - Escera, C.
Journal: Neuroimage

The Mismatch Negativity (MMN) component of the event-related potentials is generated when a detectable spectrotemporal feature of the incoming sound does not match the sensory model set up by preceding repeated stimuli. MMN is enhanced at frontocentral scalp sites for deviant words when compared to acoustically similar deviant pseudowords, suggesting that automatic access to long-term memory traces for spoken words contributes to MMN generation. Does spectrotemporal feature matching also drive automatic lexical access? To test this, we recorded human auditory event-related potentials (ERPs) to disyllabic spoken words and pseudowords within a passive oddball paradigm. We first aimed at replicating the word-related MMN enhancement effect for Spanish, thereby adding to the available cross-linguistic evidence (e.g., Finnish, English). We then probed its resilience to spectrotemporal perturbation by inserting short (20 ms) and long (120 ms) silent gaps between first and second syllables of deviant and standard stimuli. A significantly enhanced, frontocentrally distributed MMN to deviant words was found for stimuli with no gap. The long gap yielded no deviant word MMN, showing that prior expectations of word form limits in a given language influence deviance detection processes. Crucially, the insertion of a short gap suppressed deviant word MMN enhancement at frontocentral sites. We propose that spectrotemporal point-wise matching constitutes a core mechanism for fast serial computations in audition and language, bridging sensory and long-term memory systems.

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The anterior left inferior frontal gyrus contributes to semantic unification.

Publication Date: 2012 May 1 PMID: 22387168
Authors: Zhu, Z. - Hagoort, P. - Zhang, J. X. - Feng, G. - Chen, H. C. - Bastiaansen, M. - Wang, S.
Journal: Neuroimage

Semantic unification, the process by which small blocks of semantic information are combined into a coherent utterance, has been studied with various types of tasks. However, whether the brain activations reported in these studies are attributed to semantic unification per se or to other task-induced concomitant processes still remains unclear. The neural basis for semantic unification in sentence comprehension was examined using event-related potentials (ERP) and functional Magnetic Resonance Imaging (fMRI). The semantic unification load was manipulated by varying the goodness of fit between a critical word and its preceding context (in high cloze, low cloze and violation sentences). The sentences were presented in a serial visual presentation mode. The participants were asked to perform one of three tasks: semantic congruency judgment (SEM), silent reading for comprehension (READ), or font size judgment (FONT), in separate sessions. The ERP results showed a similar N400 amplitude modulation by the semantic unification load across all of the three tasks. The brain activations associated with the semantic unification load were found in the anterior left inferior frontal gyrus (aLIFG) in the FONT task and in a widespread set of regions in the other two tasks. These results suggest that the aLIFG activation reflects a semantic unification, which is different from other brain activations that may reflect task-specific strategic processing.

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Evaluating reverse speech as a control task with language-related gamma activity on electrocorticography.

Publication Date: 2012 May 1 PMID: 22387167
Authors: Brown, E. C. - Muzik, O. - Rothermel, R. - Matsuzaki, N. - Juhasz, C. - Shah, A. K. - Atkinson, M. D. - Fuerst, D. - Mittal, S. - Sood, S. - Diwadkar, V. A. - Asano, E.
Journal: Neuroimage

Reverse speech has often been used as a control task in brain-mapping studies of language utilizing various non-invasive modalities. The rationale is that reverse speech is comparable to forward speech in terms of auditory characteristics, while omitting the linguistic components. Thus, it may control for non-language auditory functions. This finds some support in fMRI studies indicating that reverse speech resulted in less blood-oxygen-level-dependent (BOLD) signal intensity in perisylvian regions than forward speech. We attempted to externally validate a reverse speech control task using intracranial electrocorticography (ECoG) in eight patients with intractable focal epilepsy. We studied adolescent and adult patients who underwent extraoperative ECoG prior to resective epilepsy surgery. All patients received an auditory language task during ECoG recording. Patients were presented 115 audible question stimuli, including 30 reverse speech trials. Reverse speech trials more strongly engaged bilateral superior temporal sites than did the corresponding forward speech trials. Forward speech trials elicited larger gamma-augmentation at frontal lobe sites not attributable to sensorimotor function. Other temporal and frontal sites of significant augmentation showed no significant difference between reverse and forward speech. Thus, we failed to validate reported evidence of weaker activation of temporal neocortices during reverse compared to forward speech. Superior temporal lobe engagement may indicate increased attention to reverse speech. Reverse speech does not appear to be a suitable task for the control of non-language auditory functions on ECoG.

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Cortical networks for vision and language in dyslexic and normal children of variable socio-economic status.

Publication Date: 2012 May 15 PMID: 22387166
Authors: Monzalvo, K. - Fluss, J. - Billard, C. - Dehaene, S. - Dehaene-Lambertz, G.
Journal: Neuroimage

In dyslexia, anomalous activations have been described in both left temporo-parietal language cortices and in left ventral visual occipito-temporal cortex. However, the reproducibility, task-dependency, and presence of these brain anomalies in childhood rather than adulthood remain debated. We probed the large-scale organization of ventral visual and spoken language areas in dyslexic children using minimal target-detection tasks that were performed equally well by all groups. In 23 normal and 23 dyslexic 10-year-old children from two different socio-economic status (SES) backgrounds, we compared fMRI activity to visually presented houses, faces, and written strings, and to spoken sentences in the native or in a foreign language. Our results confirm a disorganization of both ventral visual and spoken language areas in dyslexic children. Visually, dyslexic children showed a normal lateral-to-medial mosaic of preferences, as well as normal responses to houses and checkerboards, but a reduced activation to words in the visual word form area (VWFA) and to faces in the right fusiform face area (FFA). Auditorily, dyslexic children exhibited reduced responses to speech in posterior temporal cortex, left insula and supplementary motor area, as well as reduced responses to maternal language in subparts of the planum temporale, left basal language area and VWFA. By correlating these two findings, we identify spoken-language predictors of VWFA activation to written words, which differ for dyslexic and normal readers. Similarities in fMRI deficits in both SES groups emphasize the existence of a core set of brain activation anomalies in dyslexia, regardless of culture, language and SES, without however resolving whether these anomalies are a cause or a consequence of impaired reading.

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Characterisation of partial volume effect and region-based correction in small animal positron emission tomography (PET) of the rat brain.

Publication Date: 2012 May 1 PMID: 22387126
Authors: Lehnert, W. - Gregoire, M. C. - Reilhac, A. - Meikle, S. R.
Journal: Neuroimage

Accurate quantification of PET imaging data is required for a useful interpretation of the measured radioactive tracer concentrations. The partial volume effect (PVE) describes signal dilution and mixing due to spatial resolution and sampling limitations, which introduces bias in quantitative results. In the present study we investigated the magnitude of PVE for volumes of interest (VOIs) in the rat brain and the effect of positron range. In simulated (11)C-raclopride studies we examined the influence of PVE on time activity curves in striatal and cerebellar VOIs and binding potential estimation. The performance of partial volume correction (PVC) was studied using the region-based geometric transfer matrix (GTM) method including the question of whether a spatially variant point spread function (PSF) is necessary for PVC of a rat brain close to the centre of the field of view. Furthermore, we determined the effect of spillover from activity outside the brain. The results confirmed that PVE is significant in rat brain PET and showed that positron range is an important factor that needs to be included in the PSF. There was considerable bias in time activity curves for the simulated (11)C-raclopride studies and significant underestimation of binding potential even for very small centred VOIs. Good activity recovery was achieved with the GTM PVC using a spatially invariant simulated PSF when no activity was present outside the brain. PVC using a simple Gaussian fit point spread function was not sufficiently accurate. Spillover from regions outside the brain had a significant impact on measured activity concentrations and reduced the accuracy of PVC with the GTM method using rat brain regions alone, except for the smallest VOI size but at the cost of increased noise. Voxel-based partial volume correction methods which inherently compensate for spillover from outside the brain might be a more suitable choice.

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Spatiotemporal dynamics of the brain at rest--exploring EEG microstates as electrophysiological signatures of BOLD resting state networks.

Publication Date: 2012 May 1 PMID: 22381593
Authors: Yuan, H. - Zotev, V. - Phillips, R. - Drevets, W. C. - Bodurka, J.
Journal: Neuroimage

Neuroimaging research suggests that the resting cerebral physiology is characterized by complex patterns of neuronal activity in widely distributed functional networks. As studied using functional magnetic resonance imaging (fMRI) of the blood-oxygenation-level dependent (BOLD) signal, the resting brain activity is associated with slowly fluctuating hemodynamic signals (~10s). More recently, multimodal functional imaging studies involving simultaneous acquisition of BOLD-fMRI and electroencephalography (EEG) data have suggested that the relatively slow hemodynamic fluctuations of some resting state networks (RSNs) evinced in the BOLD data are related to much faster (~100 ms) transient brain states reflected in EEG signals, that are referred to as "microstates". To further elucidate the relationship between microstates and RSNs, we developed a fully data-driven approach that combines information from simultaneously recorded, high-density EEG and BOLD-fMRI data. Using independent component analysis (ICA) of the combined EEG and fMRI data, we identified thirteen microstates and ten RSNs that are organized independently in their temporal and spatial characteristics, respectively. We hypothesized that the intrinsic brain networks that are active at rest would be reflected in both the EEG data and the fMRI data. To test this hypothesis, the rapid fluctuations associated with each microstate were correlated with the BOLD-fMRI signal associated with each RSN. We found that each RSN was characterized further by a specific electrophysiological signature involving from one to a combination of several microstates. Moreover, by comparing the time course of EEG microstates to that of the whole-brain BOLD signal, on a multi-subject group level, we unraveled for the first time a set of microstate-associated networks that correspond to a range of previously described RSNs, including visual, sensorimotor, auditory, attention, frontal, visceromotor and default mode networks. These results extend our understanding of the electrophysiological signature of BOLD RSNs and demonstrate the intrinsic connection between the fast neuronal activity and slow hemodynamic fluctuations.

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Within-subject joint independent component analysis of simultaneous fMRI/ERP in an auditory oddball paradigm.

Publication Date: 2012 May 1 PMID: 22377443
Authors: Mangalathu-Arumana, J. - Beardsley, S. A. - Liebenthal, E.
Journal: Neuroimage

The integration of event-related potential (ERP) and functional magnetic resonance imaging (fMRI) can contribute to characterizing neural networks with high temporal and spatial resolution. This research aimed to determine the sensitivity and limitations of applying joint independent component analysis (jICA) within-subjects, for ERP and fMRI data collected simultaneously in a parametric auditory frequency oddball paradigm. In a group of 20 subjects, an increase in ERP peak amplitude ranging 1-8 muV in the time window of the P300 (350-700 ms), and a correlated increase in fMRI signal in a network of regions including the right superior temporal and supramarginal gyri, was observed with the increase in deviant frequency difference. JICA of the same ERP and fMRI group data revealed activity in a similar network, albeit with stronger amplitude and larger extent. In addition, activity in the left pre- and post-central gyri, likely associated with right hand somato-motor response, was observed only with the jICA approach. Within-subject, the jICA approach revealed significantly stronger and more extensive activity in the brain regions associated with the auditory P300 than the P300 linear regression analysis. The results suggest that with the incorporation of spatial and temporal information from both imaging modalities, jICA may be a more sensitive method for extracting common sources of activity between ERP and fMRI.

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The neuromagnetic response to spoken sentences: co-modulation of theta band amplitude and phase.

Publication Date: 2012 May 1 PMID: 22374481
Authors: Howard, M. F. - Poeppel, D.
Journal: Neuroimage

Speech elicits a phase-locked response in the auditory cortex that is dominated by theta (3-7 Hz) frequencies when observed via magnetoencephalography (MEG). This phase-locked response is potentially explained as new phase-locked activity superimposed on the ongoing theta oscillation or, alternatively, as phase-resetting of the ongoing oscillation. The conventional method used to distinguish between the two hypotheses is the comparison of post- to prestimulus amplitude for the phase-locked frequency across a set of trials. In theory, increased amplitude indicates the presence of additive activity, while unchanged amplitude points to phase-resetting. However, this interpretation may not be valid if the amplitude of ongoing background activity also changes following the stimulus. In this study, we employ a new approach that circumvents this problem. Specifically, we utilize a fine-grained time-frequency analysis of MEG channel data to examine the co-modulation of amplitude change and phase coherence in the post-stimulus theta-band response. If the phase-locked response is attributable solely to phase-resetting of the ongoing theta oscillation, then amplitude and phase coherence should be uncorrelated. In contrast, additive activity should produce a positive correlation. We find significant positive correlation not only during the onset response but also throughout the response period. In fact, transient increases in phase coherence are accompanied by transient increases in amplitude in accordance with a "signal plus background" model of the evoked response. The results support the hypothesis that the theta-band phase-locked response to attended speech observed using MEG is dominated by additive phase-locked activity.

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The neural mechanisms of affect infusion in social economic decision-making: A mediating role of the anterior insula.

Publication Date: 2012 May 15 PMID: 22374480
Authors: Harle, K. M. - Chang, L. J. - van 't Wout, M. - Sanfey, A. G.
Journal: Neuroimage

Though emotions have been shown to have sometimes dramatic effects on decision-making, the neural mechanisms mediating these biases are relatively unexplored. Here, we investigated how incidental affect (i.e. emotional states unrelated to the decision at hand) may influence decisions, and how these biases are implemented in the brain. Nineteen adult participants made decisions which involved accepting or rejecting monetary offers from others in an Ultimatum Game while undergoing functional magnetic resonance imaging (fMRI). Prior to each set of decisions, participants watched a short video clip aimed at inducing either a sad or neutral emotional state. Results demonstrated that, as expected, sad participants rejected more unfair offers than those in the neutral condition. Neuroimaging analyses revealed that receiving unfair offers while in a sad mood elicited activity in brain areas related to aversive emotional states and somatosensory integration (anterior insula) and to cognitive conflict (anterior cingulate cortex). Sad participants also showed a diminished sensitivity in neural regions associated with reward processing (ventral striatum). Importantly, insular activation uniquely mediated the relationship between sadness and decision bias. This study is the first to reveal how subtle mood states can be integrated at the neural level to influence decision-making.

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Bridging the hemispheres in meditation: Thicker callosal regions and enhanced fractional anisotropy (FA) in long-term practitioners.

Publication Date: 2012 May 15 PMID: 22374478
Authors: Luders, E. - Phillips, O. R. - Clark, K. - Kurth, F. - Toga, A. W. - Narr, K. L.
Journal: Neuroimage

Recent findings suggest a close link between long-term meditation practices and the structure of the corpus callosum. Prior analyses, however, have focused on estimating mean fractional anisotropy (FA) within two large pre-defined callosal tracts only. Additional effects might exist in other, non-explored callosal regions and/or with respect to callosal attributes not captured by estimates of FA. To further explore callosal features in the framework of meditation, we analyzed 30 meditators and 30 controls, carefully matched for sex, age, and handedness. We applied a multimodal imaging approach using diffusion tensor imaging (DTI) in combination with structural magnetic resonance imaging (MRI). Callosal measures of tract-specific FA were complemented with other global (segment-specific) estimates as well as extremely local (point-wise) measures of callosal micro- and macro-structure. Callosal measures were larger in long-term meditators compared to controls, particularly in anterior callosal sections. However, differences achieved significance only when increasing the regional sensitivity of the measurement (i.e., using point-wise measures versus segment-specific measures) and were more prominent for microscopic than macroscopic characteristics (i.e., callosal FA versus callosal thickness). Thicker callosal regions and enhanced FA in meditators might indicate greater connectivity, possibly reflecting increased hemispheric integration during cerebral processes involving (pre)frontal regions. Such a brain organization might be linked to achieving characteristic mental states and skills as associated with meditation, though this hypothesis requires behavioral confirmation. Moreover, longitudinal studies are required to address whether the observed callosal effects are induced by meditation or constitute an innate prerequisite for the start or successful continuation of meditation.

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Sex differences in amygdala subregions: evidence from subregional shape analysis.

Publication Date: 2012 May 1 PMID: 22374477
Authors: Kim, H. J. - Kim, N. - Kim, S. - Hong, S. - Park, K. - Lim, S. - Park, J. M. - Na, B. - Chae, Y. - Lee, J. - Yeo, S. - Choe, I. H. - Cho, S. Y. - Cho, G.
Journal: Neuroimage

Each subregion of the amygdala is characterized by a distinct cytoarchitecture and function. However, most previous studies on sexual dimorphism and aging have assessed differences in the structure of the amygdala at the level of the amygdala in its entirety rather than at the subregional level. Using an amygdala subregional shape analysis, we investigated the effects of sex, age, and the sex x age interaction on the subregion after controlling for intracranial volume. We found the main effect of age in the subregions and the effect of sex in the superficial nucleus, which showed that men had a larger mean radius than women. We also found a sex x age interaction in the centromedial nucleus, in that the radius of the centromedial nucleus showed a steeper decline with age in women compared with men. Regarding the amygdala volume as a whole, we found only an age effect and did not find any other significant difference between genders. The sex difference in the amygdala subregion and its relevance to the circulating gonadal hormone were discussed.

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The correlation between brain gray matter volume and empathizing and systemizing quotients in healthy children.

Publication Date: 2012 May 1 PMID: 22369996
Authors: Sassa, Y. - Taki, Y. - Takeuchi, H. - Hashizume, H. - Asano, M. - Asano, K. - Wakabayashi, A. - Kawashima, R.
Journal: Neuroimage

The abilities to empathize and to systemize, two fundamental dimensions of cognitive style, are characterized by apparent individual differences. These abilities are typically measured using an empathizing quotient (EQ) and a systemizing quotient (SQ) questionnaire, respectively. The purpose of this study was to reveal any correlations between EQ and SQ scores and regional gray matter volumes in healthy children by applying voxel-based morphometry to magnetic resonance images. We collected MRIs of brain structure and administered children's versions of the EQ and SQ questionnaires (EQ-C and SQ-C, respectively) to 261 healthy children aged 5-15 years. Structural MRI data were segmented, normalized, and smoothed using an optimized voxel-based morphometric analysis. Next, we analyzed the correlation between regional gray matter volume and EQ-C and SQ-C scores adjusting for age, sex, and intracranial volume. The EQ-C scores showed significant positive correlations with the regional gray matter volumes of the left fronto-opercular and superior temporal cortices, including the precentral gyrus, the inferior frontal gyrus, the superior temporal gyrus, and the insula, which are functionally related to empathic processing. Additionally, SQ-C scores showed a significant negative correlation with the regional gray matter volume of the left posterior parietal cortex, which is functionally involved in selective attention processing. Our findings suggest that individual differences in cognitive style pertaining to empathizing or systemizing abilities could be explained by differences in the volume of brain structures that are functionally relevant to empathizing and systemizing.

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A framework to integrate EEG-correlated fMRI and intracerebral recordings.

Publication Date: 2012 May 1 PMID: 22369995
Authors: van Houdt, P. J. - Ossenblok, P. P. - Colon, A. J. - Boon, P. A. - de Munck, J. C.
Journal: Neuroimage

EEG-correlated functional MRI (EEG-fMRI) has been used to indicate brain regions associated with interictal epileptiform discharges (IEDs). This technique enables the delineation of the complete epileptiform network, including multifocal and deeply situated cortical areas. Before EEG-fMRI can be used as an additional diagnostic tool in the preoperative work-up, its added value should be assessed in relation to intracranial EEG recorded from depth electrodes (SEEG) or from the cortex (ECoG), currently the clinical standard. In this study, we propose a framework for the analysis of the SEEG data to investigate in a quantitative way whether EEG-fMRI reflects the same cortical areas as identified by the IEDs present in SEEG recordings. For that purpose, the data of both modalities were analyzed with a general linear model at the same time scale and within the same spatial domain. The IEDs were used as predictors in the model, yielding for EEG-fMRI the brain voxels that were related to the IEDs and, similarly for SEEG, the electrodes that were involved. Finally, the results of the regression analysis were projected on the anatomical MRI of the patients. To explore the usefulness of this quantitative approach, a sample of five patients was studied who both underwent EEG-fMRI and SEEG recordings. For clinical validation, the results of the SEEG analysis were compared to the standard visual review of IEDs in SEEG and to the identified seizure onset zone, the resected area, and outcome of surgery. SEEG analysis revealed a spatial pattern for the most frequent and dominant IEDs present in the data of all patients. The electrodes with the highest correlation values were in good concordance with the electrodes that showed maximal amplitude during those events in the SEEG recordings. These results indicate that the analysis of SEEG data at the time scale of EEG-fMRI, using the same type of regression model, is a promising way to validate EEG-fMRI data. In fact, the BOLD areas with a positive hemodynamic response function were closely related to the spatial pattern of IEDs in the SEEG recordings in four of the five patients. The areas of significant BOLD that were not located in the vicinity of depth electrodes, were mainly characterized by negative hemodynamic responses. Furthermore, the area with a positive hemodynamic response function overlapped with the resected area in three patients, while it was located at the edge of the resection area for one. To conclude, the results of this study encourage the application of EEG-fMRI to guide the implantation of depth electrodes as prerequisite for successful epilepsy surgery.

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Rule and similarity in grammar: their interplay and individual differences in the brain.

Publication Date: 2012 May 1 PMID: 22369994
Authors: Hauser, M. F. - Hofmann, J. - Opitz, B.
Journal: Neuroimage

Previous research on artificial grammar has indicated that the human ability to classify sentences or letter strings according to grammaticality relies on two types of knowledge. One is a superficial, familiarity-based understanding of a grammar the other is the knowledge of rules and critical features underlying a grammar. The fundamentally different characteristics of these systems permit an analysis of receiver-operating characteristics (ROC), which measures the extent to which each type of knowledge is used in grammaticality judgments. Furthermore, violations of a grammar can be divided into hierarchical and local violations. The present study is the first to combine the use of ROC analyses, fMRI and a grammaticality dichotomy. Based on previous neuroimaging studies, it was hypothesized that judgments based on rule knowledge, as extracted from individual ROC analyses, involve the left inferior frontal gyrus (IFG), whereas similarity would involve right IFG, as well as left hippocampal regions. With regards to violation types, it was hypothesized that hierarchical violations would recruit the opercular part of the left IFG as well as the posterior operculum, whereas local violations would bilaterally activate the premotor cortex (PMC). Results indicated that for greater reliance on rule knowledge, a ventral part of the left PMC was activated for ungrammatical items, whereas other PMC areas show a differentiated response for grammaticality for individuals less reliant on similarity. The right IFG was related to ungrammatical items as a function of similarity. Results are discussed with regards to possible error detection systems and differentiated efficiencies for respective classification strategies.

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Decoding covert spatial attention using electrocorticographic (ECoG) signals in humans.

Publication Date: 2012 May 1 PMID: 22366333
Authors: Gunduz, A. - Brunner, P. - Daitch, A. - Leuthardt, E. C. - Ritaccio, A. L. - Pesaran, B. - Schalk, G.
Journal: Neuroimage

This study shows that electrocorticographic (ECoG) signals recorded from the surface of the brain provide detailed information about shifting of visual attention and its directional orientation in humans. ECoG allows for the identification of the cortical areas and time periods that hold the most information about covert attentional shifts. Our results suggest a transient distributed fronto-parietal mechanism for orienting of attention that is represented by different physiological processes. This neural mechanism encodes not only whether or not a subject shifts their attention to a location, but also the locus of attention. This work contributes to our understanding of the electrophysiological representation of attention in humans. It may also eventually lead to brain-computer interfaces (BCIs) that optimize user interaction with their surroundings or that allow people to communicate choices simply by shifting attention to them.

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Age effects on the P300 potential and the corresponding fMRI BOLD-signal.

Publication Date: 2012 May 1 PMID: 22366332
Authors: Juckel, G. - Karch, S. - Kawohl, W. - Kirsch, V. - Jager, L. - Leicht, G. - Lutz, J. - Stammel, A. - Pogarell, O. - Ertl, M. - Reiser, M. - Hegerl, U. - Moller, H. J. - Mulert, C.
Journal: Neuroimage

Age has been reported to influence amplitude and latency of the P300 potential. Nevertheless, it is not yet fully understood which brain regions are responsible for these effects. The aim of this study was to investigate age-effects on the P300 potential and the simultaneously acquired BOLD signal of functional MRI. 32 healthy male subjects were investigated using an auditory oddball paradigm. The functional MRI data were acquired in temporal synchrony to the task. The evoked potential data were recorded during the intervals in between MR image acquisitions in order to reduce the influence of the scanner noise on the presentation of the tones and to reduce gradient artifacts. The age-effects were calculated by means of regression analyses. In addition, brain regions modulated by the task-induced amplitude variation of the P300 were identified (single trial analysis). The results indicated an age effect on the P300 amplitude. Younger subjects demonstrated increased parietal P300 amplitudes and increased BOLD responses in a network of brain regions including the anterior and posterior cingulate cortex, the insula, the temporo-parietal junction, the superior temporal gyrus, the caudate body, the amygdala and the parahippocampal gyrus. Single trial coupling of EEG and fMRI indicated that P300 amplitudes were predominantly associated with neural responses in the anterior cingulate cortex, the putamen and temporal brain areas. Taken together, the results indicate diminished neural responses in older compared to younger subjects especially in frontal, temporo-parietal and subcortical brain regions.

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Quantitative comparison of resting-state functional connectivity derived from fNIRS and fMRI: a simultaneous recording study.

Publication Date: 2012 May 1 PMID: 22366082
Authors: Duan, L. - Zhang, Y. J. - Zhu, C. Z.
Journal: Neuroimage

The feasibility of functional near-infrared spectroscopy (fNIRS) to assess resting-state functional connectivity (RSFC) has already been demonstrated. However the validity of fNIRS-based RSFC has rarely been studied. In the present study, fNIRS and fMRI data were simultaneously acquired from 21 subjects during the resting state. After the spatial correspondence was established between the two imaging modalities by transforming the fMRI data into fNIRS measurements space, the index of Between-Modality-Similarity (BMS) of RSFC was evaluated across multiple spatial scales. First, the RSFC between the bilateral primary motor ROI was quite similar between fNIRS and fMRI for all the subjects (BMS(ROI) = 0.95 +/- 0.04 for HbO and BMS(ROI) = 0.86 +/- 0.13 for HbR). Second, group-level sensorimotor RSFC maps (0.79 for HbO and 0.74 for HbR) showed higher between-modality similarity than individual-level RSFC maps (0.48 +/- 0.16 for HbO and 0.41 +/- 0.15 for HbR). Finally, for the first time, we combined fNIRS and graph theory to investigate topological properties of resting-state brain networks. The clustering coefficient (C(p)) and characteristic path length (L(p)) which are the most important network topological parameters, both showed high between-modality similarities (BMS(Cp) = 0.90 +/- 0.03 for HbO and 0.90 +/- 0.06 for HbR; BMS(Lp) = 0.92 +/- 0.04 for HbO and 0.91 +/- 0.05 for HbR). In summary, the converged results across all the spatial scales demonstrated that fNIRS is capable of providing comparable RSFC measures to fMRI, and thus provide direct evidence for the validity of the optical brain connectivity and the optical brain network approaches to functional brain integration during resting state.

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Enhancing reproducibility of fMRI statistical maps using generalized canonical correlation analysis in NPAIRS framework.

Publication Date: 2012 May 1 PMID: 22366080
Authors: Afshin-Pour, B. - Hossein-Zadeh, G. A. - Strother, S. C. - Soltanian-Zadeh, H.
Journal: Neuroimage

Common fMRI data processing techniques usually minimize a temporal cost function or fit a temporal model to extract an activity map. Here, we focus on extracting a highly, spatially reproducible statistical parametric map (SPM) from fMRI data using a cost function that does not depend on a model of the subjects' temporal response. Based on a generalized version of canonical correlation analysis (gCCA), we propose a method to extract a highly reproducible map by maximizing the sum of pair-wise correlations between some maps. In a group analysis, each map is calculated from a linear combination of fMRI scans of a subset of subjects under study. The proposed method is applied to BOLD fMRI datasets without any spatial smoothing from 10 subjects performing a simple reaction time (RT) task. Using the NPAIRS split-half resampling framework with a reproducibility measure based on SPM correlations, we compare the proposed approach with canonical variate analysis (CVA) and a simple general linear model (GLM). gCCA provides statistical parametric maps with higher reproducibility than CVA and GLM with correlation reproducibilities across independent split-half SPMs of 0.78, 0.46, and 0.41, respectively. Our results show that gCCA is an efficient approach for extracting the default mode network, assessing brain connectivity, and processing event-related and resting-state datasets in which the temporal BOLD signal varies from subject to subject.

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Changes in reward-related signals in the rat nucleus accumbens measured by in vivo oxygen amperometry are consistent with fMRI BOLD responses in man.

Publication Date: 2012 May 1 PMID: 22361256
Authors: Francois, J. - Conway, M. W. - Lowry, J. P. - Tricklebank, M. D. - Gilmour, G.
Journal: Neuroimage

Real-time in vivo oxygen amperometry, a technique that allows measurement of regional brain tissue oxygen (O(2)) has been previously shown to bear relationship to the BOLD signal measured with functional magnetic resonance imaging (fMRI) protocols. In the present study, O(2) amperometry was applied to the study of reward processing in the rat nucleus accumbens to validate the technique with a behavioural process known to cause robust signals in human neuroimaging studies. After acquisition of a cued-lever pressing task a robust increase in O(2) tissue levels was observed in the nucleus accumbens specifically following a correct lever press to the rewarded cue. This O(2) signal was modulated by cue reversal but not lever reversal, by differences in reward magnitudes and by the motivational state of the animal consistent with previous reports of the role of the nucleus accumbens in both the anticipation and representation of reward value. Moreover, this modulation by reward value was related more to the expected incentive value rather than the hedonic value of reward, also consistent with previous reports of accumbens coding of "wanting" of reward. Altogether, these results show striking similarities to those obtained in human fMRI studies suggesting the use of oxygen amperometry as a valid surrogate for fMRI in animals performing cognitive tasks, and a powerful approach to bridge between different techniques of measurement of brain function.

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State-dependent attention modulation of human primary visual cortex: a high density ERP study.

Publication Date: 2012 May 1 PMID: 22361168
Authors: Rossi, V. - Pourtois, G.
Journal: Neuroimage

Converging electrophysiological and brain-imaging results show that sensory processing in V1 can be modulated by attention. In this study, we tested the prediction that this early filtering effect depends on the current affective state of the participant. We recorded visual evoked potentials (VEPs) to visual peripheral distractors while participants performed a demanding task at fixation, whose perceptual load was manipulated in a parametric fashion. Crucially, levels of negative affect were either increased or decreased independently of changes in perceptual load. Concurrent psychophysiological measurements and self-report scales confirmed that changes in emotional state were effective. In the control condition, ERP results showed that the C1 component generated in response to the exact same peripheral distractors systematically varied in amplitude with the amount of perceptual load imposed at fixation, being larger when perceptual load decreased. However, this early modulatory effect in V1 was disrupted when participants transiently experienced increased state anxiety, resulting in a decreased C1 amplitude even though task load at fixation remained low. These results suggest that early bottom-up processing in V1 is not only influenced by the amount of attention resources available, but also by the current internal state of the participant.

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The role of the left anterior temporal lobe in exception word reading: reconciling patient and neuroimaging findings.

Publication Date: 2012 May 1 PMID: 22361167
Authors: Wilson, M. A. - Joubert, S. - Ferre, P. - Belleville, S. - Ansaldo, A. I. - Joanette, Y. - Rouleau, I. - Brambati, S. M.
Journal: Neuroimage

Semantic dementia (SD) is a neurodegenerative disease that occurs following the atrophy of the anterior temporal lobes (ATLs). It is characterised by the degradation of semantic knowledge and difficulties in reading exception words (surface dyslexia). This disease has highlighted the role of the ATLs in the process of exception word reading. However, imaging studies in healthy subjects have failed to detect activation of the ATLs during exception word reading. The aim of the present study was to test whether the functional brain regions that mediate exception word reading in normal readers overlap those brain regions atrophied in SD. In Study One, we map the brain regions of grey matter atrophy in AF, a patient with mild SD and surface dyslexia profile. In Study Two, we map the activation pattern associated with exception word compared to pseudoword reading in young, healthy participants using fMRI. The results revealed areas of significant activation in healthy subjects engaged in the exception word reading task in the left anterior middle temporal gyrus, in a region observed to be atrophic in the patient AF. These results reconcile neuropsychological and functional imaging data, revealing the critical role of the left ATL in exception word reading.

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Dissociable large-scale networks anchored in the right anterior insula subserve affective experience and attention.

Publication Date: 2012 May 1 PMID: 22361166
Authors: Touroutoglou, A. - Hollenbeck, M. - Dickerson, B. C. - Feldman Barrett, L.
Journal: Neuroimage

Meta-analytic summaries of neuroimaging studies point to at least two major functional-anatomic subdivisions within the anterior insula that contribute to the detection and processing of salient information: a dorsal region that is routinely active during attention tasks and a ventral region that is routinely active during affective experience. In two independent samples of cognitively normal human adults, we used intrinsic functional connectivity magnetic resonance imaging to demonstrate that the right dorsal and right ventral anterior insula are nodes in separable large-scale functional networks. Furthermore, stronger intrinsic connectivity within the right dorsal anterior insula network was associated with better performance on a task involving attention and processing speed whereas stronger connectivity within the right ventral anterior insula network was associated with more intense affective experience. These results support the hypothesis that the identification and manipulation of salient information is subserved by at least two brain networks anchored in the right anterior insula that exhibit distinct large-scale topography and dissociable behavioral correlates.

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Enhanced early-latency electromagnetic activity in the left premotor cortex is associated with successful phonetic categorization.

Publication Date: 2012 May 1 PMID: 22361165
Authors: Alho, J. - Sato, M. - Sams, M. - Schwartz, J. L. - Tiitinen, H. - Jaaskelainen, I. P.
Journal: Neuroimage

Sensory-motor interactions between auditory and articulatory representations in the dorsal auditory processing stream are suggested to contribute to speech perception, especially when bottom-up information alone is insufficient for purely auditory perceptual mechanisms to succeed. Here, we hypothesized that the dorsal stream responds more vigorously to auditory syllables when one is engaged in a phonetic identification/repetition task subsequent to perception compared to passive listening, and that this effect is further augmented when the syllables are embedded in noise. To this end, we recorded magnetoencephalography while twenty subjects listened to speech syllables, with and without noise masking, in four conditions: passive perception; overt repetition; covert repetition; and overt imitation. Compared to passive listening, left-hemispheric N100m equivalent current dipole responses were amplified and shifted posteriorly when perception was followed by covert repetition task. Cortically constrained minimum-norm estimates showed amplified left supramarginal and angylar gyri responses in the covert repetition condition at ~100ms from stimulus onset. Longer-latency responses at ~200ms were amplified in the covert repetition condition in the left angular gyrus and in all three active conditions in the left premotor cortex, with further enhancements when the syllables were embedded in noise. Phonetic categorization accuracy and magnitude of voice pitch change between overt repetition and imitation conditions correlated with left premotor cortex responses at ~100 and ~200ms, respectively. Together, these results suggest that the dorsal stream involvement in speech perception is dependent on perceptual task demands and that phonetic categorization performance is influenced by the left premotor cortex.

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Delayed monitoring of accuracy errors compared to commission errors in ACC.

Publication Date: 2012 May 1 PMID: 22353628
Authors: Bediou, B. - Koban, L. - Rosset, S. - Pourtois, G. - Sander, D.
Journal: Neuroimage

Error detection is essential for monitoring performance and preparing subsequent behavioral adjustments, and is associated with specific neural responses in the anterior cingulate cortex (ACC). To investigate whether different brain mechanisms subserve the processing of commission vs. accuracy errors, we recorded EEG in adult participants while they performed a novel speeded GO-NOGO aiming task ("the Shoot-NoShoot paradigm"). Our ERP results show that commission errors (responding during NOGO trials) elicited a classical error-related negativity (ERN) component, followed by an error-related positivity (Pe), as well as a negativity peaking before response onset (pre-ERN). By contrast, spatial accuracy errors elicited a feedback-related negativity (FRN), which correlated with the spatial discrepancy between response and target position across subjects. Fast hits also elicited a pre-ERN but no ERN, suggesting that this pre-response monitoring component might be related to the detection of error likelihood. Although source analysis revealed similar generators in ACC for these different error-related negativities, the respective timing differed, suggesting that commission errors are detected rapidly based on internal motor representations, whereas the detection of accuracy errors in ACC relies on the additional and swift processing of external visual information.

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Using confirmatory factor analysis to measure contemporaneous activation of defined neuronal networks in functional magnetic resonance imaging.

Publication Date: 2012 May 1 PMID: 22348884
Authors: Lahey, B. B. - McNealy, K. - Knodt, A. - Zald, D. H. - Sporns, O. - Manuck, S. B. - Flory, J. D. - Applegate, B. - Rathouz, P. J. - Hariri, A. R.
Journal: Neuroimage

Functional neuroimaging often generates large amounts of data on regions of interest. Such data can be addressed effectively with a widely-used statistical technique based on measurement theory that has not yet been applied to neuroimaging. Confirmatory factor analysis is a convenient hypothesis-driven modeling environment that can be used to conduct formal statistical tests comparing alternative hypotheses regarding the elements of putative neuronal networks. In such models, measures of each activated region of interest are treated as indicators of an underlying latent construct that represents the contemporaneous activation of the elements in the network. As such, confirmatory factor analysis focuses analyses on the activation of hypothesized networks as a whole, improves statistical power by modeling measurement error, and provides a theory-based approach to data reduction with a robust statistical basis. This approach is illustrated using data on seven regions of interest in a hypothesized mesocorticostriatal reward system in a sample of 262 adult volunteers assessed during a card-guessing reward task. A latent construct reflecting contemporaneous activation of the reward system was found to be significantly associated with a latent construct measuring impulsivity, particularly in males.

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EEG correlates of haptic feedback in a visuomotor tracking task.

Publication Date: 2012 May 1 PMID: 22348883
Authors: Lin, C. L. - Shaw, F. Z. - Young, K. Y. - Lin, C. T. - Jung, T. P.
Journal: Neuroimage

This study investigates the temporal brain dynamics associated with haptic feedback in a visuomotor tracking task. Haptic feedback with deviation-related forces was used throughout tracking experiments in which subjects' behavioral responses and electroencephalogram (EEG) data were simultaneously measured. Independent component analysis was employed to decompose the acquired EEG signals into temporally independent time courses arising from distinct brain sources. Clustering analysis was used to extract independent components that were comparable across participants. The resultant independent brain processes were further analyzed via time-frequency analysis (event-related spectral perturbation) and event-related coherence (ERCOH) to contrast brain activity during tracking experiments with or without haptic feedback. Across subjects, in epochs with haptic feedback, components with equivalent dipoles in or near the right motor region exhibited greater alpha band power suppression. Components with equivalent dipoles in or near the left frontal, central, left motor, right motor, and parietal regions exhibited greater beta-band power suppression, while components with equivalent dipoles in or near the left frontal, left motor, and right motor regions showed greater gamma-band power suppression relative to non-haptic conditions. In contrast, the right occipital component cluster exhibited less beta-band power suppression in epochs with haptic feedback compared to non-haptic conditions. The results of ERCOH analysis of the six component clusters showed that there were significant increases in coherence between different brain networks in response to haptic feedback relative to the coherence observed when haptic feedback was not present. The results of this study provide novel insight into the effects of haptic feedback on the brain and may aid the development of new tools to facilitate the learning of motor skills.

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Mesolimbic dopamine release is linked to symptom severity in pathological gambling.

Publication Date: 2012 May 1 PMID: 22348881
Authors: Joutsa, J. - Johansson, J. - Niemela, S. - Ollikainen, A. - Hirvonen, M. M. - Piepponen, P. - Arponen, E. - Alho, H. - Voon, V. - Rinne, J. O. - Hietala, J. - Kaasinen, V.
Journal: Neuroimage

BACKGROUND: Brain dopamine neurons code rewarding environmental stimuli by releasing endogenous dopamine, a transmission signal that is important for reinforcement learning. Human reward-seeking gambling behavior, and especially pathological gambling, has been presumed to be modulated by brain dopamine. METHODS: Striatal dopamine release was studied with [(11)C]raclopride positron emission tomography (PET) during gambling with an ecologically valid slot machine gambling task. Twenty-four males with and without pathological gambling (DSM-IV) were scanned three times, and the effects of different gambling outcomes (high-reward and low-reward vs. control task) on dopamine release were evaluated. RESULTS: Striatal dopamine was released in both groups during high-reward but also low-reward tasks. The dopamine release during the low-reward task was located in the associative part of the caudate nucleus. During the high-reward task, the effect was also seen in the ventral striatum and the magnitude of dopamine release was associated with parallel gambling "high". Furthermore, there was a positive correlation between dopamine release during the low-reward and the high-reward task. There was no general difference in the magnitude of dopamine release between pathological gamblers and controls. However, in pathological gamblers, dopamine release correlated positively with gambling symptom severity. CONCLUSIONS: Striatal dopamine is released during gambling irrespective of gambling outcome suggesting that the mere expectation/prediction of reward is sufficient to induce dopaminergic changes. Although dopamine release during slot machine gambling is comparable between healthy controls and pathological gamblers, greater gambling symptom severity is associated with greater dopaminergic responses. Thus, as the dopamine reward deficiency theory predicts blunted mesolimbic dopamine responses to gambling in addicted individuals, our results question the validity of the reward deficiency hypothesis in pathological gambling.

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Correlations between FDG PET glucose uptake-MRI gray matter volume scores and apolipoprotein E epsilon4 gene dose in cognitively normal adults: a cross-validation study using voxel-based multi-modal partial least squares.

Publication Date: 2012 May 1 PMID: 22348880
Authors: Chen, K. - Ayutyanont, N. - Langbaum, J. B. - Fleisher, A. S. - Reschke, C. - Lee, W. - Liu, X. - Alexander, G. E. - Bandy, D. - Caselli, R. J. - Reiman, E. M.
Journal: Neuroimage

We previously introduced a voxel-based, multi-modal application of the partial least square algorithm (MMPLS) to characterize the linkage between patterns in a person's complementary complex datasets without the need to correct for multiple regional comparisons. Here we used it to demonstrate a strong correlation between MMPLS scores to characterize the linkage between the covarying patterns of fluorodeoxyglucose positron emission tomography (FDG PET) measurements of regional glucose metabolism and magnetic resonance imaging (MRI) measurements of regional gray matter associated with apolipoprotein E (APOE) epsilon4 gene dose (i.e., three levels of genetic risk for late-onset Alzheimer's disease (AD)) in cognitively normal, late-middle-aged persons. Coregistered and spatially normalized FDG PET and MRI images from 70% of the subjects (27 epsilon4 homozygotes, 36 epsilon4 heterozygotes and 67 epsilon4 non-carriers) were used in a hypothesis-generating MMPLS analysis to characterize the covarying pattern of regional gray matter volume and cerebral glucose metabolism most strongly correlated with APOE-epsilon4 gene dose. Coregistered and spatially normalized FDG PET and MRI images from the remaining 30% of the subjects were used in a hypothesis-testing MMPLS analysis to generate FDG PET-MRI gray matter MMPLS scores blind to their APOE genotype and characterize their relationship to APOE-epsilon4 gene dose. The hypothesis-generating analysis revealed covarying regional gray matter volume and cerebral glucose metabolism patterns that resembled those in traditional univariate analyses of AD and APOE-epsilon4 gene dose and PET-MRI scores that were strongly correlated with APOE-epsilon4 gene dose (p<1 x 10(-16)). The hypothesis-testing analysis results showed strong correlations between FDG PET-MRI gray matter scores and APOE-epsilon4 gene dose (p = 8.7 x 10(-4)). Our findings support the possibility of using the MMPLS to analyze complementary datasets from the same person in the presymptomatic detection and tracking of AD.

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On the use of correlation as a measure of network connectivity.

Publication Date: 2012 May 1 PMID: 22343126
Authors: Zalesky, A. - Fornito, A. - Bullmore, E.
Journal: Neuroimage

Numerous studies have demonstrated that brain networks derived from neuroimaging data have nontrivial topological features, such as small-world organization, modular structure and highly connected hubs. In these studies, the extent of connectivity between pairs of brain regions has often been measured using some form of statistical correlation. This article demonstrates that correlation as a measure of connectivity in and of itself gives rise to networks with non-random topological features. In particular, networks in which connectivity is measured using correlation are inherently more clustered than random networks, and as such are more likely to be small-world networks. Partial correlation as a measure of connectivity also gives rise to networks with non-random topological features. Partial correlation networks are inherently less clustered than random networks. Network measures in correlation networks should be benchmarked against null networks that respect the topological structure induced by correlation measurements. Prevalently used random rewiring algorithms do not yield appropriate null networks for some network measures. Null networks are proposed to explicitly normalize for the inherent topological structure found in correlation networks, resulting in more conservative estimates of small-world organization. A number of steps may be needed to normalize each network measure individually and control for distinct features (e.g. degree distribution). The main conclusion of this article is that correlation can and should be used to measure connectivity, however appropriate null networks should be used to benchmark network measures in correlation networks.

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The timing of exploratory decision-making revealed by single-trial topographic EEGanalyses.

Publication Date: 2012 May 1 PMID: 22342874
Authors: Tzovara, A. - Murray, M. M. - Bourdaud, N. - Chavarriaga, R. - Millan Jdel, R. - De Lucia, M.
Journal: Neuroimage

Decision-making in an uncertain environment is driven by two major needs: exploring the environment to gather information or exploiting acquired knowledge to maximize reward. The neural processes underlying exploratory decision-making have been mainly studied by means of functional magnetic resonance imaging, overlooking any information about the time when decisions are made. Here, we carried out an electroencephalography (EEG) experiment, in order to detect the time when the brain generators responsible for these decisions have been sufficiently activated to lead to the next decision. Our analyses, based on a classification scheme, extract time-unlocked voltage topographies during reward presentation and use them to predict the type of decisions made on the subsequent trial. Classification accuracy, measured as the area under the Receiver Operator's Characteristic curve was on average 0.65 across 7 subjects. Classification accuracy was above chance levels already after 516 ms on average, across subjects. We speculate that decisions were already made before this critical period, as confirmed by a positive correlation with reaction times across subjects. On an individual subject basis, distributed source estimations were performed on the extracted topographies to statistically evaluate the neural correlates of decision-making. For trials leading to exploration, there was significantly higher activity in dorsolateral prefrontal cortex and the right supramarginal gyrus; areas responsible for modulating behavior under risk and deduction. No area was more active during exploitation. We show for the first time the temporal evolution of differential patterns of brain activation in an exploratory decision-making task on a single-trial basis.

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Distinct functional networks within the cerebellum and their relation to cortical systems assessed with independent component analysis.

Publication Date: 2012 May 1 PMID: 22342804
Authors: Dobromyslin, V. I. - Salat, D. H. - Fortier, C. B. - Leritz, E. C. - Beckmann, C. F. - Milberg, W. P. - McGlinchey, R. E.
Journal: Neuroimage

Cerebellar functional circuitry has been examined in several prior studies using resting fMRI data and seed-based procedures, as well as whole-brain independent component analysis (ICA). Here, we hypothesized that ICA applied to functional data from the cerebellum exclusively would provide increased sensitivity for detecting cerebellar networks compared to previous approaches. Consistency of group-level networks was assessed in two age- and sex-matched groups of twenty-five subjects each. Cerebellum-only ICA was compared to the traditional whole-brain ICA procedure to examine the potential gain in sensitivity of the novel method. In addition to replicating a number of previously identified cerebellar networks, the current approach revealed at least one network component that was not apparent with the application of whole brain ICA. These results demonstrate the gain in sensitivity attained through specifying the cerebellum as a target structure with regard to the identification of robust and reliable networks. The use of similar procedures could be important in further expanding on previously defined patterns of cerebellar functional anatomy, as well as provide information about unique networks that have not been explored in prior work. Such information may prove crucial for understanding the cognitive and behavioral importance of the cerebellum in health and disease.

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Genetic variation in CYP2A6 predicts neural reactivity to smoking cues as measured using fMRI.

Publication Date: 2012 May 1 PMID: 22342802
Authors: Tang, D. W. - Hello, B. - Mroziewicz, M. - Fellows, L. K. - Tyndale, R. F. - Dagher, A.
Journal: Neuroimage

Smoking cues trigger craving for cigarettes and relapse. Nicotine metabolism, mediated by the enzyme CYP2A6, also influences smoking behavior. In this study, we investigated how nicotine metabolism and genetic variation in CYP2A6 influence the neural response to smoking cues in humans using functional magnetic resonance imaging (fMRI). We hypothesized that individuals with faster rates of nicotine metabolism would have stronger conditioned responses to smoking cues because of closer coupling in everyday life between exposure to cigarettes and surges in blood nicotine concentration. In contrast, individuals with reduced rates of metabolism, who have relatively constant nicotine blood levels throughout the day, should be less likely to develop conditioned responses to cues. We screened 169 smokers for their rate of nicotine metabolism and CYP2A6 genotype, and selected 31 smokers with the fastest and slowest rates for fMRI, matched for daily cigarette intake. We measured their neural response to visual smoking and non-smoking cues using fMRI. As predicted, fast metabolizers, by phenotype or genotype, had significantly greater responses to visual cigarette cues than slow metabolizers in the amygdala, hippocampus, striatum, insula, and cingulate cortex. These results support the theory that drug cues are conditioned stimuli, and explain why fast metabolizers who smoke have lower cessation rates. They also provide insight into how genetics can shape human vulnerability to addiction, and have implications for tailoring smoking cessation programs based on individual genetics.

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Spatiotemporal mapping of brain atrophy in mouse models of Huntington's disease using longitudinal in vivo magnetic resonance imaging.

Publication Date: 2012 May 1 PMID: 22342677
Authors: Aggarwal, M. - Duan, W. - Hou, Z. - Rakesh, N. - Peng, Q. - Ross, C. A. - Miller, M. I. - Mori, S. - Zhang, J.
Journal: Neuroimage

Mouse models of Huntington's disease (HD) that recapitulate some of the phenotypic features of human HD, play a crucial role in investigating disease mechanisms and testing potential therapeutic approaches. Longitudinal studies of these models can yield valuable insights into the temporal course of disease progression and the effect of drug treatments on the progressive phenotypes. Atrophy of the brain, particularly the striatum, is a characteristic phenotype of human HD, is known to begin long before the onset of motor symptoms, and correlates strongly with clinical features. Elucidating the spatial and temporal patterns of atrophy in HD mouse models is important to characterize the phenotypes of these models, as well as evaluate the effects of neuroprotective treatments at specific time frames during disease progression. In this study, three dimensional in vivo magnetic resonance imaging (MRI) and automated longitudinal deformation-based morphological analysis was used to elucidate the spatial and temporal patterns of brain atrophy in the R6/2 and N171-82Q mouse models of HD. Using an established MRI-based brain atlas and mixed-effects modeling of deformation-based metrics, we report the rates of progression and region-specificity of brain atrophy in the two models. Further, the longitudinal analysis approach was used to evaluate the effects of sertraline and coenzyme Q(10) (CoQ(10)) treatments on progressive atrophy in the N171-82Q model. Sertraline treatment resulted in significant slowing of atrophy, especially in the striatum and frontal cortex regions, while no significant effects of CoQ(10) treatment were observed. Progressive cortical and striatal atrophy in the N171-82Q mice showed significant positive correlations with measured functional deficits. The findings of this report can be used for future testing and comparison of potential therapeutics in mouse models of HD.

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Multi-projection magnetic resonance inverse imaging of the human visuomotor system.

Publication Date: 2012 May 15 PMID: 22326985
Authors: Wen-Kai Tsai, K. - Nummenmaa, A. - Witzel, T. - Chang, W. T. - Kuo, W. J. - Lin, F. H.
Journal: Neuroimage

Using highly parallel radiofrequency (RF) detection, magnetic resonance inverse imaging (InI) can achieve 100ms temporal resolution with whole brain coverage. This is achieved by trading off partition encoding steps and thus spatial resolution for a higher acquisition rate. The reduced spatial information is estimated by solving under-determined inverse problems using RF coil sensitivity information. Here we propose multi projection inverse imaging (mInI) to combine different projection images to improve the spatial resolution of InI. Specifically, coronal, sagittal, and transverse projection images were acquired from different runs of the fMRI acquisitions using a 32-channel head coil array. Simulations show that mInI improves the quality of the instantaneous image reconstruction significantly. Going from one projection to three projections, the spatial resolution quantified by the full width at half maximum of the point-spread function (PSF) is improved from 2.6 pixels to 1.4 pixels (4mm nominal resolution per pixel). Considering the shape of the PSF, the effective spatial resolution is improved from 16.9 pixels to 4.7 pixels. In vivo fMRI experiments using a two-choice reaction time tasks show visual and sensorimotor cortical activities spatially consistent with typical EPI data, yet mInI offers 100ms temporal resolution with the whole brain coverage. The mInI data with three projections revealed that the sensorimotor cortex was activated 700ms after the visual cortex. mInI can be applied to BOLD-contrast fMRI experiments to characterize the dynamics of the activated brain areas with a high spatiotemporal resolution.

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A geographical history of social cognitive neuroscience.

Publication Date: 2012 Jun PMID: 22309803
Authors: Lieberman, M. D.
Journal: Neuroimage

The history of social cognitive neuroscience (SCN) began with isolated islands of research in Europe and the United States in the 1990s. In the decade between 1995 and 2004 most of the major areas of current SCN research were identified in a series of high profile first studies. This paper reviews the timeline as well as the geography of important moments in the short history of this field. Of note is the different focus seen in European contributions (theory of mind, mirror neurons, and empathy) and the more self-focused U.S. contributions (self-knowledge, emotion regulation, implicit attitudes).

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Interaction of COMT val158met and externalizing behavior: relation to prefrontal brain activity and behavioral performance.

Publication Date: 2012 May 1 PMID: 22306803
Authors: Shehzad, Z. - DeYoung, C. G. - Kang, Y. - Grigorenko, E. L. - Gray, J. R.
Journal: Neuroimage

A promising approach in neuroimaging studies aimed at understanding effects of single genetic variants on behavior is the study of gene-trait interactions. Variation in the catechol-O-methyl-transferase gene (COMT) is associated with the regulation of dopamine levels in the prefrontal cortex and with cognitive functioning. Given the involvement of dopaminergic neurotransmission in externalizing behavior, a trait characterized by impulsivity and aggression, especially in men, externalizing (as a trait) may index a set of genetic, environmental, and neural characteristics pertinent to understanding phenotypic effects of genetic variation in the COMT gene. In the current study, we used a gene-trait approach to investigate effects of the COMT val(158)met polymorphism and externalizing on brain activity during moments involving low or high demands on cognitive control. In 104 male participants, interference-related activation depended conjointly on externalizing and val(158)met: stronger activation in the dorsal anterior cingulate and lateral prefrontal cortex was found for val/val individuals with high trait externalizing while stronger activation in cingulate motor areas and sensorimotor precuneus was found for met/met individuals with low externalizing. Our results suggest that the val/val genotype, coupled with high levels of trait externalizing, lowers the efficiency of stimulus conflict resolution, whereas the met/met genotype, coupled with low levels of externalizing, lowers the efficiency of response selection.

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The past, present and future of social neuroscience: A European perspective.

Publication Date: 2012 Jun PMID: 22305955
Authors: Singer, T.
Journal: Neuroimage

This review provides an overview of the field of social neuroscience from a European perspective and focuses mainly on outlining research topics which originated in European laboratories. After a brief historical synopsis of the emergence of this young field, the most relevant findings related to the investigation of the neural networks underlying our capacity to understand the minds of others are summarized. More specifically, three routes of social cognition are distinguished: (1) our capacity to mentalize, or to infer intentions and beliefs of others, (2) our capacity to mimic and understand other's motor actions, and (3) our capacity to empathize, or to share and understand the feelings of others. More recent studies focusing on social emotions such as love, compassion, revenge or our sense of fairness will be discussed linking the field of social neuroscience to the even younger field of neuroeconomics, with the focus on the study of human social interactions using game theoretical paradigms. Finally, the use of a multi-method and multi-disciplinary research approach combining genetic, pharmacological, computational and developmental aspects is advocated and future directions for the study of interactive minds are discussed.

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Distributed processing; distributed functions?

Publication Date: 2012 Jun PMID: 22245638
Authors: Fox, P. T. - Friston, K. J.
Journal: Neuroimage

After more than twenty years busily mapping the human brain, what have we learned from neuroimaging? This review (coda) considers this question from the point of view of structure-function relationships and the two cornerstones of functional neuroimaging; functional segregation and integration. Despite remarkable advances and insights into the brain's functional architecture, the earliest and simplest challenge in human brain mapping remains unresolved: We do not have a principled way to map brain function onto its structure in a way that speaks directly to cognitive neuroscience. Having said this, there are distinct clues about how this might be done: First, there is a growing appreciation of the role of functional integration in the distributed nature of neuronal processing. Second, there is an emerging interest in data-driven cognitive ontologies, i.e., that are internally consistent with functional anatomy. We will focus this review on the growing momentum in the fields of functional connectivity and distributed brain responses and consider this in the light of meta-analyses that use very large data sets to disclose large-scale structure-function mappings in the human brain.

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Coma and consciousness: Paradigms (re)framed by neuroimaging.

Publication Date: 2012 Jun PMID: 22227888
Authors: Laureys, S. - Schiff, N. D.
Journal: Neuroimage

The past 15years have provided an unprecedented collection of discoveries that bear upon our scientific understanding of recovery of consciousness in the human brain following severe brain damage. Highlighted among these discoveries are unique demonstrations that patients with little or no behavioral evidence of conscious awareness may retain critical cognitive capacities and the first scientific demonstrations that some patients, with severely injured brains and very longstanding conditions of limited behavioral responsiveness, may nonetheless harbor latent capacities for significant recovery. Included among such capacities are particularly human functions of language and higher-level cognition that either spontaneously or through direct interventions may reemerge even at long time intervals or remain unrecognized. Collectively, these observations have reframed scientific inquiry and further led to important new insights into mechanisms underlying consciousness in the human brain. These studies support a model of consciousness as the emergent property of the collective behavior of widespread frontoparietal network connectivity modulated by specific forebrain circuit mechanisms. We here review these advances in measurement and the scientific and broader implications of this rapidly progressing field of research.

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The neurochemical profile quantified by in vivo(1)H NMR spectroscopy.

Publication Date: 2012 Jun PMID: 22227137
Authors: Duarte, J. M. - Lei, H. - Mlynarik, V. - Gruetter, R.
Journal: Neuroimage

Proton NMR spectroscopy is emerging from translational and preclinical neuroscience research as an important tool for evidence based diagnosis and therapy monitoring. It provides biomarkers that offer fingerprints of neurological disorders even in cases where a lesion is not yet observed in MR images. The collection of molecules used as cerebral biomarkers that are detectable by (1)H NMR spectroscopy define the so-called "neurochemical profile". The non-invasive quality of this technique makes it suitable not only for diagnostic purposes but also for therapy monitoring paralleling an eventual neuroprotection. The application of (1)H NMR spectroscopy in basic and translational neuroscience research is discussed here.

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Towards the utilization of EEG as a brain imaging tool.

Publication Date: 2012 Jun PMID: 22227136
Authors: Michel, C. M. - Murray, M. M.
Journal: Neuroimage

Recent advances in signal analysis have engendered EEG with the status of a true brain mapping and brain imaging method capable of providing spatio-temporal information regarding brain (dys)function. Because of the increasing interest in the temporal dynamics of brain networks, and because of the straightforward compatibility of the EEG with other brain imaging techniques, EEG is increasingly used in the neuroimaging community. However, the full capability of EEG is highly underestimated. Many combined EEG-fMRI studies use the EEG only as a spike-counter or an oscilloscope. Many cognitive and clinical EEG studies use the EEG still in its traditional way and analyze grapho-elements at certain electrodes and latencies. We here show that this way of using the EEG is not only dangerous because it leads to misinterpretations, but it is also largely ignoring the spatial aspects of the signals. In fact, EEG primarily measures the electric potential field at the scalp surface in the same way as MEG measures the magnetic field. By properly sampling and correctly analyzing this electric field, EEG can provide reliable information about the neuronal activity in the brain and the temporal dynamics of this activity in the millisecond range. This review explains some of these analysis methods and illustrates their potential in clinical and experimental applications.

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The motor system and its disorders.

Publication Date: 2012 Jun PMID: 22227135
Authors: Rowe, J. B. - Siebner, H. R.
Journal: Neuroimage

The motor system has been intensively studied using the emerging neuroimaging technologies over the last twenty years. These include early applications of positron emission tomography of brain perfusion, metabolic rate and receptor function, as well as functional magnetic resonance imaging, tractography from diffusion weighted imaging, and transcranial magnetic stimulation. Motor system research has the advantage of the existence of extensive electrophysiological and anatomical information from comparative studies which enables cross-validation of new methods. We review the impact of neuroimaging on the understanding of diverse motor functions, including motor learning, decision making, inhibition and the mirror neuron system. In addition, we show how imaging of the motor system has supported a powerful platform for bidirectional translational neuroscience. In one direction, it has provided the opportunity to study safely the processes of neuroplasticity, neural networks and neuropharmacology in stroke and movement disorders and offers a sensitive tool to assess novel therapeutics. In the reverse direction, imaging of clinical populations has promoted innovations in cognitive theory, experimental design and analysis. We highlight recent developments in the analysis of structural and functional connectivity in the motor system; the advantages of integration of multiple methodologies; and new approaches to experimental design using formal models of cognitive-motor processes.

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Imaging attention networks.

Publication Date: 2012 Jun PMID: 22227132
Authors: Posner, M. I.
Journal: Neuroimage

The study of attention has largely been about how to select among the various sensory events but also involves the selection among conflicting actions. Prior to the late 1980s, locating bottlenecks between sensory input and response dominated these studies, a different view was that attentional limits involved the importance of maintaining behavioral coherence rather than resulting from a bottleneck. In both cases ideas of resource limits taken over from economics were important. Early evidence relating to the anatomy of attention came from neurological investigations of lesioned patients, but the major impetus for the anatomical approach came from neuroimaging studies that provided evidence of brain networks related to orienting to sensory events and control of response tendencies. The presence of a functional anatomy has supported studies of the development of attention networks and the role of neuromodulators and genetic polymorphisms in their construction. Together these developments have enhanced our understanding of attention and paved the way for significant applications to education, pathology and prevention of mental illness.

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Oxygen metabolism, oxygen extraction and positron emission tomography: Historical perspective and impact on basic and clinical neuroscience.

Publication Date: 2012 Jun PMID: 22227130
Authors: Baron, J. C. - Jones, T.
Journal: Neuroimage

Oxygen utilization is central to the human brain's high metabolic rate. Measurement of this fundamental process, in both disease and health, has been a focus of research attention over the last 35years. This review plots the course of the use of oxygen-15 to study regional cerebral oxygen extraction and metabolism using Positron Emission Tomography (PET) in disease and in health. The scientific discoveries and resulting conceptual changes to both basic and clinical neuroscience, as well as the new methodological approaches brought about by this area of research, are also summarized. We conclude with a brief overview of the current status of oxygen-15 PET in neuroscience, along with our visions for future developments and applications.

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PET radiotracers for molecular imaging in the brain: Past, present and future.

Publication Date: 2012 Jun PMID: 22222719
Authors: Zimmer, L. - Luxen, A.
Journal: Neuroimage

Neuroimaging of brain receptors began in the early 1980s. Now, some thirty-five years later, PET imaging is still an expanding field of preclinical and clinical investigations. In addition to improvements in PET cameras and image analysis, the availability of suitable radiotracers is a crucial factor leading this expansion. Radiotracers have been developed to visualize and quantify a growing numbers of brain receptors, transporters, enzymes and other molecular targets. The development of adequate PET radiotracers represents an exciting challenge, given the large number of targets and neurochemical functions that have yet to be explored. In this article, we review the main evolutions led by preclinical radiotracers and clinical radiopharmaceuticals. The current main contributions of PET radiotracers are described in terms of imaging of neuronal metabolism, receptor and transporter quantification and neurodegenerative, neuroinflammatory and neurooncologic process imaging. In the last part, we highlight some applications presenting a potential for novel functional explorations of the brain.

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Imaging brain development: The adolescent brain.

Publication Date: 2012 Jun PMID: 22178817
Authors: Blakemore, S. J.
Journal: Neuroimage

The past 15years has seen a rapid expansion in the number of studies using neuroimaging techniques to investigate maturational changes in the human brain. In this paper, I review MRI studies on structural changes in the developing brain, and fMRI studies on functional changes in the social brain during adolescence. Both MRI and fMRI studies point to adolescence as a period of continued neural development. In the final section, I discuss a number of areas of research that are just beginning and may be the subject of developmental neuroimaging in the next twenty years. Future studies might focus on complex questions including the development of functional connectivity; how gender and puberty influence adolescent brain development; the effects of genes, environment and culture on the adolescent brain; development of the atypical adolescent brain; and implications for policy of the study of the adolescent brain.

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Brain imaging in the study of Alzheimer's disease.

Publication Date: 2012 Jun PMID: 22173295
Authors: Reiman, E. M. - Jagust, W. J.
Journal: Neuroimage

Over the last 20years, there has been extraordinary progress in brain imaging research and its application to the study of Alzheimer's disease (AD). Brain imaging researchers have contributed to the scientific understanding, early detection and tracking of AD. They have set the stage for imaging techniques to play growing roles in the clinical setting, the evaluation of disease-modifying treatments, and the identification of demonstrably effective prevention therapies. They have developed ground-breaking methods, including positron emission tomography (PET) ligands to measure fibrillar amyloid-beta (Abeta) deposition, new magnetic resonance imaging (MRI) pulse sequences, and powerful image analysis techniques, to help in these endeavors. Additional work is needed to develop even more powerful imaging methods, to further clarify the relationship and time course of Abeta and other disease processes in the predisposition to AD, to establish the role of brain imaging methods in the clinical setting, and to provide the scientific means and regulatory approval pathway needed to evaluate the range of promising disease-modifying and prevention therapies as quickly as possible. Twenty years from now, AD may not yet be a distant memory, but the best is yet to come.

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Magnetoencephalography: From SQUIDs to neuroscience: Neuroimage 20th Anniversary Special Edition.

Publication Date: 2012 Jun PMID: 22166794
Authors: Hari, R. - Salmelin, R.
Journal: Neuroimage

Magnetoencephalography (MEG), with its direct view to the cortex through the magnetically transparent skull, has developed from its conception in physics laboratories to a powerful tool of basic and clinical neuroscience. MEG provides millisecond time resolution and allows real-time tracking of brain activation sequences during sensory processing, motor planning and action, cognition, language perception and production, social interaction, and various brain disorders. Current-day neuromagnetometers house hundreds of SQUIDs, superconducting quantum interference devices, to pick up signals generated by concerted action of cortical neurons. Complementary MEG measures of neuronal involvement include evoked responses, modulation of cortical rhythms, properties of the on-going neural activity, and interareal connectivity. Future MEG breakthroughs in understanding brain dynamics are expected through advanced signal analysis and combined use of MEG with hemodynamic imaging (fMRI). Methodological development progresses most efficiently when linked with insightful neuroscientific questions.

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Diffusion MRI at 25: Exploring brain tissue structure and function.

Publication Date: 2012 Jun PMID: 22120012
Authors: Le Bihan, D. - Johansen-Berg, H.
Journal: Neuroimage

Diffusion MRI (or dMRI) came into existence in the mid-1980s. During the last 25years, diffusion MRI has been extraordinarily successful (with more than 300,000 entries on Google Scholar for diffusion MRI). Its main clinical domain of application has been neurological disorders, especially for the management of patients with acute stroke. It is also rapidly becoming a standard for white matter disorders, as diffusion tensor imaging (DTI) can reveal abnormalities in white matter fiber structure and provide outstanding maps of brain connectivity. The ability to visualize anatomical connections between different parts of the brain, non-invasively and on an individual basis, has emerged as a major breakthrough for neurosciences. The driving force of dMRI is to monitor microscopic, natural displacements of water molecules that occur in brain tissues as part of the physical diffusion process. Water molecules are thus used as a probe that can reveal microscopic details about tissue architecture, either normal or in a diseased state.

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Diagnostic neuroimaging across diseases.

Publication Date: 2012 Jun PMID: 22094642
Authors: Kloppel, S. - Abdulkadir, A. - Jack, C. R. Jr - Koutsouleris, N. - Mourao-Miranda, J. - Vemuri, P.
Journal: Neuroimage

Fully automated classification algorithms have been successfully applied to diagnose a wide range of neurological and psychiatric diseases. They are sufficiently robust to handle data from different scanners for many applications and in specific cases outperform radiologists. This article provides an overview of current applications taking structural imaging in Alzheimer's disease and schizophrenia as well as functional imaging to diagnose depression as examples. In this context, we also report studies aiming to predict the future course of the disease and the response to treatment for the individual. This has obvious clinical relevance but is also important for the design of treatment studies that may aim to include a cohort with a predicted fast disease progression to be more sensitive to detect treatment effects. In the second part, we present our own opinions on i) the role these classification methods can play in the clinical setting; ii) where their limitations are at the moment and iii) how those can be overcome. Specifically, we discuss strategies to deal with disease heterogeneity, diagnostic uncertainties, a probabilistic framework for classification and multi-class classification approaches.

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Imaging semantics and syntax.

Publication Date: 2012 Jun PMID: 22019859
Authors: Cappa, S. F.
Journal: Neuroimage

This is a highly selective review of functional imaging papers, which have attempted to isolate the neural substrates of semantic and syntactic processing in the human brain. The main emphasis is historical, with a special consideration of the mutual relationship between the traditional, lesion-based approach to the neurology of language and the contributions of the tremendous development of imaging techniques of the last decades.

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