NeuroImage

Optimization of diffusion spectrum imaging and q-ball imaging on clinical MRI system.

Publication Date: 2008 May 15 PMID: 18387822
Authors: Kuo, L. W. - Chen, J. H. - Wedeen, V. J. - Tseng, W. Y.
Journal: Neuroimage

Mapping complex crossing fibers using diffusion MRI techniques requires adequate angular precision and accuracy. Beyond diffusion tensor imaging (DTI), high angular resolution sampling schemes such as diffusion spectrum imaging (DSI) and q-ball imaging (QBI) were proposed to resolve crossing fibers. These schemes require hundreds of data approximately five to ten times more than DTI, offsetting their clinical feasibility. To facilitate its clinical application, optimum values of highest diffusion sensitivity (bmax) must be investigated under the constraint of scan time and gradient performance. In this study, simulation of human data sets and a following verification experiment were performed to investigate the optimum bmax of DSI and QBI. Four sampling schemes, two with high sampling number, i.e., DSI515 and QBI493, and two with low sampling number, i.e., DSI203 and QBI253, were compared. Deviation angle and angular dispersion were used to evaluate the precision and accuracy among different bmax of each scheme. The results indicated that the optimum bmax was a trade-off between SNR and angular resolution. At their own optimum bmax, the reduced sampling schemes yielded angular precision and accuracy comparable to the high sampling schemes. On our current 3 T system, the optimum bmax (s/mm(2)) were 6500 for DSI515, 4000 for DSI203, 3000 for QBI493 and 2500 for QBI253. DSI was incrementally more accurate than QBI, but required a greater demand for gradient performance. In conclusion, our systematic study of optimum bmax in different sampling schemes and the consideration derived wherein could be helpful to determine optimum sampling schemes in other MRI systems.

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Anatomical substrates of cooperative joint-action in a continuous motor task: Virtual lifting and balancing.

Publication Date: 2008 May 15 PMID: 18378467
Authors: Newman-Norlund, R. D. - Bosga, J. - Meulenbroek, R. G. - Bekkering, H.
Journal: Neuroimage

An emerging branch of social cognitive neuroscience attempts to unravel the critical cognitive mechanisms that enable humans to engage in joint action. In the current experiment, differences in brain activity in participants engaging in solitary action and joint action were identified using whole brain fMRI while participants performed a virtual bar-balancing task either alone (S), or with the help of a partner in each of two separate joint-action conditions (isomorphic [J(i)] and non-isomorphic [J(n)]). Compared to the performing the task alone, BOLD signal was found to be stronger in both joint-action conditions at specific sites in the human mirror system (MNS). This activation pattern may reflect the demand on participants to simulate the actions of others, integrate their own actions with those of their partners, and compute appropriate responses. Increasing inter-dependence (complementarity) of movements being generated by cooperating individuals (J(n)>J(i)>S) was found to correlate with BOLD signal in the right anterior node of the MNS (pars opercularis), and the area around the right temporoparietal junction (TPJ). These data are relevant to current debates concerning the role of right IFG in complementary action, as well as evolving theories of joint action.

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Effects of feature-selective attention on auditory pattern and location processing.

Publication Date: 2008 May 15 PMID: 18378168
Authors: Altmann, C. F. - Henning, M. - Doring, M. K. - Kaiser, J.
Journal: Neuroimage

Recent neuroimaging studies have suggested that spatial versus nonspatial changes in acoustic stimulation are processed along separate cortical pathways. However, it has remained unclear in how far change-related responses are modulated by selective attention. Thus, we aimed at testing effects of feature-selective attention on the cortical representation of pattern and location of complex natural sounds using human functional magnetic resonance imaging (fMRI) adaptation. We consecutively presented the following pairs of animal vocalizations: (a) two identical animal vocalizations, (b) same animal vocalizations at different locations, (c) different animal vocalizations at the same location, and (d) different animal vocalizations at different locations. Subjects underwent this stimulation under two different task conditions requiring either to match sound identity or location. We observed significant fMRI adaptation effects within the bilateral superior temporal sulcus (STS), planum temporale (PT) and right anterior insula for location changes. For pattern changes, we found adaptation effects within the bilateral superior temporal lobe, in particular along the superior temporal gyrus (STG), PT and posterior STS, the bilateral anterior insula and inferior frontal areas. While the adaptation effects within the pattern-selective temporal lobe areas were robust to task requirements, adaptation within the more posterior location-selective areas was modulated by feature-specific attention. In contrast, inferior frontal cortex and anterior insular exhibited adaptation effects mainly during the location matching task. Given that the location matching task was significantly more difficult than the pattern matching, our data suggest that frontal and insular regions were modulated by task difficulty rather than feature-specific attention.

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3D characterization of brain atrophy in Alzheimer's disease and mild cognitive impairment using tensor-based morphometry.

Publication Date: 2008 May 15 PMID: 18378167
Authors: Hua, X. - Leow, A. D. - Lee, S. - Klunder, A. D. - Toga, A. W. - Lepore, N. - Chou, Y. Y. - Brun, C. - Chiang, M. C. - Barysheva, M. - Jack, C. R. Jr - Bernstein, M. A. - Britson, P. J. - Ward, C. P. - Whitwell, J. L. - Borowski, B. - Fleisher, A. S. - Fox, N. C. - Boyes, R. G. - Barnes, J. - Harvey, D. - Kornak, J. - Schuff, N. - Boreta, L. - Alexander, G. E. - Weiner, M. W. - Thompson, P. M. - The Alzheimer's Disease Neuroimaging, I. n. i. t. i. a. t. i. v. e.
Journal: Neuroimage

Tensor-based morphometry (TBM) creates three-dimensional maps of disease-related differences in brain structure, based on nonlinearly registering brain MRI scans to a common image template. Using two different TBM designs (averaging individual differences versus aligning group average templates), we compared the anatomical distribution of brain atrophy in 40 patients with Alzheimer's disease (AD), 40 healthy elderly controls, and 40 individuals with amnestic mild cognitive impairment (aMCI), a condition conferring increased risk for AD. We created an unbiased geometrical average image template for each of the three groups, which were matched for sex and age (mean age: 76.1 years+/-7.7 SD). We warped each individual brain image (N=120) to the control group average template to create Jacobian maps, which show the local expansion or compression factor at each point in the image, reflecting individual volumetric differences. Statistical maps of group differences revealed widespread medial temporal and limbic atrophy in AD, with a lesser, more restricted distribution in MCI. Atrophy and CSF space expansion both correlated strongly with Mini-Mental State Exam (MMSE) scores and Clinical Dementia Rating (CDR). Using cumulative p-value plots, we investigated how detection sensitivity was influenced by the sample size, the choice of search region (whole brain, temporal lobe, hippocampus), the initial linear registration method (9- versus 12-parameter), and the type of TBM design. In the future, TBM may help to (1) identify factors that resist or accelerate the disease process, and (2) measure disease burden in treatment trials.

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Impaired semantic processing during sentence reading in children with dyslexia: Combined fMRI and ERP evidence.

Publication Date: 2008 May 15 PMID: 18378166
Authors: Schulz, E. - Maurer, U. - van der Mark, S. - Bucher, K. - Brem, S. - Martin, E. - Brandeis, D.
Journal: Neuroimage

Developmental dyslexia is a specific disorder of reading acquisition characterized by a phonological core deficit. Sentence reading is also impaired in dyslexic readers, but whether semantic processing deficits contribute is unclear. Combining spatially and temporally sensitive neuroimaging techniques to focus on semantic processing can provide a more comprehensive characterization of sentence reading in dyslexia. We recorded brain activity from 52 children (16 with dyslexia, 31 controls) with functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) in two separate counterbalanced sessions. The children silently read and occasionally judged simple sentences with semantically congruous or incongruous endings. fMRI and ERP activation during sentence reading and semantic processing was analyzed across all children and also by comparing children with dyslexia to controls. For sentence reading, we analyzed the response to all words in a sentence; for semantic processing, we contrasted responses to incongruous and congruous endings. Sentence reading was characterized by activation in a left-lateralized language network. Semantic processing was characterized by activation in left-hemispheric regions of the inferior frontal and superior temporal cortex and by an electrophysiological N400 effect after 240 ms with consistent left anterior source localization. Children with dyslexia showed decreased activation for sentence reading in inferior parietal and frontal regions, and for semantic processing in inferior parietal regions, and during the N400 effect. Together, this suggests that semantic impairment during sentence reading reduces dyslexic children's response in left anterior brain regions underlying the more phasic N400 effect and subsequently modulates the more sustained BOLD response in left inferior parietal regions.

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Transient and linearly graded deactivation of the human default-mode network by a visual detection task.

Publication Date: 2008 May 15 PMID: 18375149
Authors: Singh, K. D. - Fawcett, I. P.
Journal: Neuroimage

In this fMRI study, we show that an extended network of brain areas, previously described as the default-mode network, is suppressed during the performance of a global visual motion discrimination task. For the first time, we demonstrate that this network is transiently suppressed in an event-related fashion, reflecting a true negative activation compared to baseline, and that this deactivation occurs in a strongly graded fashion depending on the strength of the global motion signal. Deactivation across the network varied in an inverse linear relationship with motion coherency, demonstrating that the strongest suppression occurs for the most error-prone tasks. Deactivations were absent for the easiest of the tasks (100% coherence). We also show that the magnitude of task-related activation of the individual sub-components of the default-mode network are strongly correlated, indicating a highly integrated system. The results offer a striking indication of a rapid, highly reactive and tunable system within the brain for active suppression of this network of brain areas.

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Repetition suppression in occipital-temporal visual areas is modulated by physical rather than semantic features of objects.

Publication Date: 2008 May 15 PMID: 18375148
Authors: Chouinard, P. A. - Morrissey, B. F. - Kohler, S. - Goodale, M. A.
Journal: Neuroimage

Functional magnetic-resonance imaging was used to identify areas involved in naming objects and to examine which of these areas adapted to either physical or semantics features of objects. We presented successive pairs of objects that were either the same exemplar of an object, different exemplars of that object, or different objects. By controlling for differences in physical features between pairs of different exemplars and different objects, visual areas in the occipital-temporal cortex were subject to repetition suppression when the same exemplars of an object were repeated, but not when different exemplars of an object were repeated. This was true independent of whether or not participants named objects. Repetition suppression in visual areas appeared therefore bound to physical features. Nevertheless, repetition suppression for physical features was greater in left visual areas when objects were named, suggesting that naming, known to depend on mechanisms in the left hemisphere, may induce greater attentional modulation in the left than in the right visual areas. Taken together, we propose that the difference between our findings and those of earlier studies that report semantic influences can be explained by the failure of those studies to control for differences in the appearance of different exemplars. Left frontal areas showed repetition suppression when either the same or different exemplars of an object were repeated, but only when participants named objects. These results suggest that visual areas process information about physical features without semantic modulation by higher-order areas, and that left frontal areas process semantic features, but the engagement of these processes is task modulated.

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Music training leads to the development of timbre-specific gamma band activity.

Publication Date: 2008 May 15 PMID: 18375147
Authors: Shahin, A. J. - Roberts, L. E. - Chau, W. - Trainor, L. J. - Miller, L. M.
Journal: Neuroimage

Oscillatory gamma band activity (GBA, 30-100 Hz) has been shown to correlate with perceptual and cognitive phenomena including feature binding, template matching, and learning and memory formation. We hypothesized that if GBA reflects highly learned perceptual template matching, we should observe its development in musicians specific to the timbre of their instrument of practice. EEG was recorded in adult professional violinists and amateur pianists as well as in 4- and 5-year-old children studying piano in the Suzuki method before they commenced music lessons and 1 year later. The adult musicians showed robust enhancement of induced (non-time-locked) GBA, specifically to their instrument of practice, with the strongest effect in professional violinists. Consistent with this result, the children receiving piano lessons exhibited increased power of induced GBA for piano tones with 1 year of training, while children not taking lessons showed no effect. In comparison to induced GBA, evoked (time-locked) gamma band activity (30-90 Hz, approximately 80 ms latency) was present only in adult groups. Evoked GBA was more pronounced in musicians than non-musicians, with synchronization equally exhibited for violin and piano tones but enhanced for these tones compared to pure tones. Evoked gamma activity may index the physical properties of a sound and is modulated by acoustical training, while induced GBA may reflect higher perceptual learning and is shaped by specific auditory experiences.

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Investigating signal integration with canonical correlation analysis of fMRI brain activation data.

Publication Date: 2008 May 15 PMID: 18375146
Authors: Bruguier, A. - Preuschoff, K. - Quartz, S. - Bossaerts, P.
Journal: Neuroimage

How the brain integrates signals from specific areas has been a longstanding critical question for neurobiologists. Two recent observations suggest a new approach to fMRI data analysis of this question. First, in many instances, the brain analyzes inputs by decomposing the information along several salient dimensions. For example, earlier work demonstrated that the brain splits a monetary gamble in terms of expected reward (ER) and variance of the reward (risk) [Preuschoff, K., Bossaerts, P., Quartz, S., 2006. Neural differentiation of expected reward and risk in human subcortical structures. Neuron 51, 381-390]. However, since ER and risk activate separate brain regions, the brain needs to integrate these activations to obtain an overall evaluation of the gamble. Second, recent evidence suggests that the correlation of the activity between neurons may serve a specific organizational purpose [Romo, R., Hernandez, A., Zainos, A., Salinas, E., 2003. Correlated neuronal discharges that increase coding efficiency during perceptual discrimination. Neuron 38, 649-657; Salinas, E., Sejnowski, T.J., 2001. Correlated neuronal activity and the flow of neural information. Nat. Rev. Neurosci. 2, 539]. Specifically, it is hypothesized that correlations allow brain regions to integrate several signals in a way that minimizes noise. Under this hypothesis, we show here that canonical correlation analysis of fMRI data identifies how the signals from several regions are combined. A general linear model then verifies whether the identified combination indeed activates a projection area in the brain. We illustrate the proposed procedure on data recorded while human subjects played a simple card game. We show that the brain adds the signals of ER and risk to form a measure that activates the medial prefrontal cortex, consistent with the role of this brain structure in the evaluation of monetary gambles.

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Right temporopolar activation associated with unique perception.

Publication Date: 2008 May 15 PMID: 18374603
Authors: Asari, T. - Konishi, S. - Jimura, K. - Chikazoe, J. - Nakamura, N. - Miyashita, Y.
Journal: Neuroimage

Unique mode of perception, or the ability to see things differently from others, is one of the psychological resources required for creative mental activities. Behavioral studies using ambiguous visual stimuli have successfully induced diverse responses from subjects, and the unique responses defined in this paradigm were observed in higher frequency in the artistic population as compared to the nonartistic population. However, the neural substrates that underlie such unique perception have yet to be investigated. In the present study, ten ambiguous figures were used as stimuli. The subjects were instructed to say what the figures looked like during functional MRI scanning. The responses were classified as "frequent", "infrequent" or "unique" responses based on the appearance frequency of the same response in an independent age- and gender-matched control group. An event-related analysis contrasting unique vs. frequent responses revealed the greatest activation in the right temporal pole, which survived a whole brain multiple comparison. An alternative parametric modulation analysis was also performed to show that potentially confounding perceptual effects deriving from differences in visual stimuli make no significant contribution to this temporopolar activation. Previous neuroimaging and neuropsychological studies have shown the involvement of the temporal pole in perception-emotion linkage. Thus, our results suggest that unique perception is produced by the integration of perceptual and emotional processes, and this integration might underlie essential parts of creative mental activities.

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Putaminal activity is related to perceptual certainty.

Publication Date: 2008 May 15 PMID: 18374602
Authors: Pastor, M. A. - Macaluso, E. - Day, B. L. - Frackowiak, R. S.
Journal: Neuroimage

We have investigated the neural basis of perceptual certainty using a simple discrimination paradigm. Psychophysical experiments have shown that a pair of identical electrical stimuli to the skin or a pair of auditory clicks to the ears are consistently perceived as two separate events in time when the inter-stimulus interval (ISIs) is long, and perceived as simultaneous events when the ISIs are very short. The perceptual certainty of having received one or two stimuli decreases when the ISI lies between these two extremes and this is reflected in inconsistent reporting of the percept across trials. In two fMRI experiments, 14 healthy subjects received either paired electrical pulses delivered to the forearm (ISIs=5-110 ms) or paired auditory clicks presented binaurally (ISIs=1-20 ms). For each subject and modality, we calculated a consistency index (CI) representing the level of perceptual certainty. The task activated pre-SMA and anterior cingulate cortex, plus the cerebellum and the basal ganglia. Critically, activity in the right putamen was linearly dependent on CI for both tactile and auditory discrimination, with topographically distinct effects in the two modalities. These results support a role for the human putamen in the "automatic" perception of temporal features of tactile and auditory stimuli.

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Defining functional areas in individual human brains using resting functional connectivity MRI.

Publication Date: 2008 May 15 PMID: 18367410
Authors: Cohen, A. L. - Fair, D. A. - Dosenbach, N. U. - Miezin, F. M. - Dierker, D. - Van Essen, D. C. - Schlaggar, B. L. - Petersen, S. E.
Journal: Neuroimage

The cerebral cortex is anatomically organized at many physical scales starting at the level of single neurons and extending up to functional systems. Current functional magnetic resonance imaging (fMRI) studies often focus at the level of areas, networks, and systems. Except in restricted domains, (e.g., topographically-organized sensory regions), it is difficult to determine area boundaries in the human brain using fMRI. The ability to delineate functional areas non-invasively would enhance the quality of many experimental analyses allowing more accurate across-subject comparisons of independently identified functional areas. Correlations in spontaneous BOLD activity, often referred to as resting state functional connectivity (rs-fcMRI), are especially promising as a way to accurately localize differences in patterns of activity across large expanses of cortex. In the current report, we applied a novel set of image analysis tools to explore the utility of rs-fcMRI for defining wide-ranging functional area boundaries. We find that rs-fcMRI patterns show sharp transitions in correlation patterns and that these putative areal boundaries can be reliably detected in individual subjects as well as in group data. Additionally, combining surface-based analysis techniques with image processing algorithms allows automated mapping of putative areal boundaries across large expanses of cortex without the need for prior information about a region's function or topography. Our approach reliably produces maps of bounded regions appropriate in size and number for putative functional areas. These findings will hopefully stimulate further methodological refinements and validations.

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Labeling of ambiguous subvoxel fibre bundle configurations in high angular resolution diffusion MRI.

Publication Date: 2008 May 15 PMID: 18367409
Authors: Savadjiev, P. - Campbell, J. S. - Descoteaux, M. - Deriche, R. - Pike, G. B. - Siddiqi, K.
Journal: Neuroimage

Whereas high angular resolution reconstruction methods for diffusion MRI can estimate multiple dominant fibre orientations within a single imaging voxel, they are fundamentally limited in certain cases of complex subvoxel fibre structures, resulting in ambiguous local orientation distribution functions. In this article we address the important problem of disambiguating such complex subvoxel fibre tract configurations, with the purpose of improving the performance of fibre tractography. We do so by extending a curve inference method to distinguish between the cases of curving and fanning fibre bundles using differential geometric estimates in a local neighbourhood. The key benefit of this method is the inference of curves, instead of only fibre orientations, to model the underlying fibre bundles. This in turn allows distinct fibre geometries that contain nearly identical sets of fibre orientations at a voxel, to be distinguished from one another. Experimental results demonstrate the ability of the method to successfully label voxels into one of the above categories and improve the performance of a fibre-tracking algorithm.

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Functional brain correlates of heterosexual paedophilia.

Publication Date: 2008 May 15 PMID: 18358744
Authors: Schiffer, B. - Paul, T. - Gizewski, E. - Forsting, M. - Leygraf, N. - Schedlowski, M. - Kruger, T. H.
Journal: Neuroimage

Although the neuronal mechanisms underlying normal sexual motivation and function have recently been examined, the alterations in brain function in deviant sexual behaviours such as paedophilia are largely unknown. The objective of this study was to identify paedophilia-specific functional networks implicated in sexual arousal. Therefore a consecutive sample of eight paedophile forensic inpatients, exclusively attracted to females, and 12 healthy age-matched heterosexual control participants from a comparable socioeconomic stratum participated in a visual sexual stimulation procedure during functional magnetic resonance imaging. The visual stimuli were sexually stimulating photographs and emotionally neutral photographs. Immediately after the imaging session subjective responses pertaining to sexual desire were recorded. Principally, the brain response of heterosexual paedophiles to heteropaedophilic stimuli was comparable to that of heterosexual males to heterosexual stimuli, including different limbic structures (amygdala, cingulate gyrus, and hippocampus), the substantia nigra, caudate nucleus, as well as the anterior cingulate cortex, different thalamic nuclei, and associative cortices. However, responses to visual sexual stimulation were found in the orbitofrontal cortex in healthy heterosexual males, but not in paedophiles, in whom abnormal activity in the dorsolateral prefrontal cortex was observed. Thus, in line with clinical observations and neuropsychological studies, it seems that central processing of sexual stimuli in heterosexual paedophiles may be altered by a disturbance in the prefrontal networks, which, as has already been hypothesized, may be associated with stimulus-controlled behaviours, such as sexual compulsive behaviours. Moreover, these findings may suggest a dysfunction (in the functional and effective connectivity) at the cognitive stage of sexual arousal processing.

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A three-dimensional MRI atlas of the zebra finch brain in stereotaxic coordinates.

Publication Date: 2008 May 15 PMID: 18358743
Authors: Poirier, C. - Vellema, M. - Verhoye, M. - Van Meir, V. - Wild, J. M. - Balthazart, J. - Van Der Linden, A.
Journal: Neuroimage

The neurobiology of birdsong, as a model for human speech, is a fast growing area of research in the neurosciences and involves electrophysiological, histological and more recently magnetic resonance imaging (MRI) approaches. Many of these studies require the identification and localization of different brain areas (nuclei) involved in the sensory and motor control of song. Until now, the only published atlases of songbird brains consisted in drawings based on histological slices of the canary and of the zebra finch brain. Taking advantage of high-magnetic field (7 Tesla) MRI technique, we present the first high-resolution (80x160x160 microm) 3-D digital atlas in stereotaxic coordinates of a male zebra finch brain, the most widely used species in the study of birdsong neurobiology. Image quality allowed us to discern most of the song control, auditory and visual nuclei. The atlas can be freely downloaded from our Web site and can be interactively explored with MRIcro. This zebra finch MRI atlas should become a very useful tool for neuroscientists working on birdsong, especially for co-registrating MRI data but also for determining accurately the optimal coordinates and angular approach for injections or electrophysiological recordings.

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Mapping the involvement of BA 4a and 4p during Motor Imagery.

Publication Date: 2008 May 15 PMID: 18358742
Authors: Sharma, N. - Jones, P. S. - Carpenter, T. A. - Baron, J. C.
Journal: Neuroimage

Motor Imagery (MI) is an attractive but intriguing means to access the motor network. There are marked inconsistencies in the functional imaging literature regarding the degree, extent and distribution of the primary motor cortex (BA 4) involvement during MI as compared to Executed Movement (EM), which may in part be related to the diverse role of BA 4 and its two subdivisions (i.e., 4a and 4p) in motor processes as well as to methodological issues. Here we used fMRI with monitoring of compliance to show that in healthy volunteers optimally screened for their ability to perform MI the contralateral BA 4 is involved during MI of a finger opposition sequence (2, 3, 4, 5; paced at 1 Hz), albeit less than during EM of the same sequence, and in a location sparing the hand area. Furthermore, both 4a and 4p subdivisions were found to be involved in MI, but the relative involvement of BA 4p appeared more robust and closer to that seen with EM. We suggest that during MI the role of BA 4 and its subdivisions may be non-executive, perhaps related to spatial encoding, though clearly further studies are needed. Finally, we report a similar hemispheric activation balance within BA 4 with both tasks, which extends the commonalities between EM and MI.

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Objective phonological and subjective perceptual characteristics of syllables modulate spatiotemporal patterns of superior temporal gyrus activity.

Publication Date: 2008 May 1 PMID: 18356082
Authors: Frye, R. E. - Fisher, J. M. - Witzel, T. - Ahlfors, S. P. - Swank, P. - Liederman, J. - Halgren, E.
Journal: Neuroimage

Natural consonant-vowel syllables are reliably classified by most listeners as voiced or voiceless. However, our previous research [Liederman, J., Frye, R., Fisher, J.M., Greenwood, K., Alexander, R., 2005. A temporally dynamic context effect that disrupts voice onset time discrimination of rapidly successive stimuli. Psychon Bull Rev. 12, 380-386] suggests that among synthetic stimuli varying systematically in voice onset time (VOT), syllables that are classified reliably as voiceless are nonetheless perceived differently within and between listeners. This perceptual ambiguity was measured by variation in the accuracy of matching two identical stimuli presented in rapid succession. In the current experiment, we used magnetoencephalography (MEG) to examine the differential contribution of objective (i.e., VOT) and subjective (i.e., perceptual ambiguity) acoustic features on speech processing. Distributed source models estimated cortical activation within two regions of interest in the superior temporal gyrus (STG) and one in the inferior frontal gyrus. These regions were differentially modulated by VOT and perceptual ambiguity. Ambiguity strongly influenced lateralization of activation; however, the influence on lateralization was different in the anterior and middle/posterior portions of the STG. The influence of ambiguity on the relative amplitude of activity in the right and left anterior STG activity depended on VOT, whereas that of middle/posterior portions of the STG did not. These data support the idea that early cortical responses are bilaterally distributed whereas late processes are lateralized to the dominant hemisphere and support a "how/what" dual-stream auditory model. This study helps to clarify the role of the anterior STG, especially in the right hemisphere, in syllable perception. Moreover, our results demonstrate that both objective phonological and subjective perceptual characteristics of syllables independently modulate spatiotemporal patterns of cortical activation.

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Five-dimensional neuroimaging: Localization of the time-frequency dynamics of cortical activity.

Publication Date: 2008 May 1 PMID: 18356081
Authors: Dalal, S. S. - Guggisberg, A. G. - Edwards, E. - Sekihara, K. - Findlay, A. M. - Canolty, R. T. - Berger, M. S. - Knight, R. T. - Barbaro, N. M. - Kirsch, H. E. - Nagarajan, S. S.
Journal: Neuroimage

The spatiotemporal dynamics of cortical oscillations across human brain regions remain poorly understood because of a lack of adequately validated methods for reconstructing such activity from noninvasive electrophysiological data. In this paper, we present a novel adaptive spatial filtering algorithm optimized for robust source time-frequency reconstruction from magnetoencephalography (MEG) and electroencephalography (EEG) data. The efficacy of the method is demonstrated with simulated sources and is also applied to real MEG data from a self-paced finger movement task. The algorithm reliably reveals modulations both in the beta band (12-30 Hz) and high gamma band (65-90 Hz) in sensorimotor cortex. The performance is validated by both across-subjects statistical comparisons and by intracranial electrocorticography (ECoG) data from two epilepsy patients. Interestingly, we also reliably observed high frequency activity (30-300 Hz) in the cerebellum, although with variable locations and frequencies across subjects. The proposed algorithm is highly parallelizable and runs efficiently on modern high-performance computing clusters. This method enables the ultimate promise of MEG and EEG for five-dimensional imaging of space, time, and frequency activity in the brain and renders it applicable for widespread studies of human cortical dynamics during cognition.

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Representing connected and disconnected shapes in human inferior intraparietal sulcus.

Publication Date: 2008 May 1 PMID: 18353688
Authors: Xu, Y.
Journal: Neuroimage

Although human lesion data have indicated the importance of the parietal cortex in object-based representations, our understanding of parietal object grouping and selection mechanisms in normal observers remains largely incomplete. This study manipulated the grouping between shapes and found that fMRI response from the inferior intraparietal sulcus (IPS) was higher for the disconnected (ungrouped) than for the connected (grouped) shapes in a task in which observers simply watched the displays and performed a simple image motion jitter detection task. These results replicated similar findings from a previous study employing a different paradigm and showed that the inferior IPS plays an important role in tracking the grouping between visual elements during visual perception. Assuming that a lower response corresponds to a greater ease of representation, these results may explain why after parietal brain lesions grouped visual elements are easier to perceive than ungrouped ones.

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A comparison of methods for the automated calculation of volumes and atrophy rates in the hippocampus.

Publication Date: 2008 May 1 PMID: 18353687
Authors: Barnes, J. - Foster, J. - Boyes, R. G. - Pepple, T. - Moore, E. K. - Schott, J. M. - Frost, C. - Scahill, R. I. - Fox, N. C.
Journal: Neuroimage

Hippocampal atrophy rates have been used in a number of studies in Alzheimer's disease (AD) to assess disease progression and are being increasingly utilized as an outcome measure in clinical trials of new pharmaceutical agents. Owing to the labor-intensive nature of hippocampal segmentation, more automated approaches are required for such analysis. In this study we compared methods of automatically segmenting the hippocampus (single-person template and template library) on the baseline image in a group of probable AD (n=36) and control (n=19) subjects with serial images. Using the method that gave most similar results to manual, three automated methods of calculating change within the hippocampal region were compared: fluid change calculated using (1) Jacobian change or (2) region propagation and (3) boundary shift. Rates were compared with manual measures. We found that segmentation of baseline hippocampus was most accurate using a template library combined with morphological operations (intensity thresholding plus one conditional dilation). This gave a voxel similarity of 0.69 (0.05) and 0.72 (0.06) in controls and probable AD subjects respectively compared with manual measures. Atrophy rates within these regions were most similar to the manual rates using the boundary shift integral (mean difference from manual rate 0.03% (1.29) in controls and 0.48% (2.44) in AD). A template library segmentation approach, together with morphological operations, provides a segmentation accurate enough to quantify relative change over time. The change over time can then be calculated automatically using boundary shift or fluid measures, with boundary shift giving most similar results to manual.

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The perception of pain in others suppresses somatosensory oscillations: A magnetoencephalography study.

Publication Date: 2008 May 1 PMID: 18353686
Authors: Cheng, Y. - Yang, C. Y. - Lin, C. P. - Lee, P. L. - Decety, J.
Journal: Neuroimage

Accumulating evidence demonstrates that similar neural circuits are activated during the first-hand experience of pain and the observation of pain in others. However, most functional MRI studies did not detect signal change in the primary somatosensory cortex during pain empathy. To test if the perception of pain in others involves the primary somatosensory cortex, neuromagnetic oscillatory activity was recorded from the primary somatosensory cortex in 16 participants while they observed static pictures depicting body parts in painful and non-painful situations. The left median nerve was stimulated at the wrist, and the poststimulus rebounds of the ~10-Hz somatosensory cortical oscillations were quantified. Compared to the baseline condition, the level of the ~10-Hz oscillations was suppressed during both of the observational situations, indicating the activation of the primary somatosensory cortex. Importantly, watching painful compared to non-painful situations suppressed somatosensory oscillations to a significant stronger degree. In addition, the suppression caused by perceiving others in the painful relative to the non-painful situations correlated with the perspective taking subscale of the interpersonal reaction index. These results, consistent with the mirror-neuron system, demonstrate that the perception of pain in others modulates neural activity in primary somatosensory cortex and supports the idea that the perception of pain in others elicits subtle somatosensory activity that may be difficult to detect by fMRI techniques.

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White matter tract integrity and intelligence in patients with mental retardation and healthy adults.

Publication Date: 2008 May 1 PMID: 18353685
Authors: Yu, C. - Li, J. - Liu, Y. - Qin, W. - Li, Y. - Shu, N. - Jiang, T. - Li, K.
Journal: Neuroimage

It is well known that brain structures correlate with intelligence but the association between the integrity of brain white matter tracts and intelligence in patients with mental retardation (MR) and healthy adults remains unknown. The aims of this study are to investigate whether the integrity of corpus callosum (CC), cingulum, uncinate fasciculus (UF), optic radiation (OR) and corticospinal tract (CST) are damaged in patients with MR, and to determine the correlations between the integrity of these tracts and full scale intelligence quotient (FSIQ) in both patients and controls. Fifteen MR patients and 79 healthy controls underwent intelligence tests and diffusion tensor imaging examinations. According to the FSIQ, all healthy controls were divided into general intelligence (GI: FSIQ<120; n=42) and high intelligence (HI: FSIQ>/=120; n=37) groups. Intelligence was assessed by Chinese Revised Wechsler Adult Intelligence Scale, and white matter tract integrity was assessed by fractional anisotropy (FA). MR patients showed significantly lower FA than healthy controls in the CC, UF, OR and CST. However, GI subjects only demonstrated lower FA than HI subjects in the right UF. Partial correlation analysis controlling for age and sex showed that FSIQ scores were significantly correlated with the FA of the bilateral UF, genu and truncus of CC, bilateral OR and left CST. While FSIQ scores were only significantly correlated with the FA of the right UF when further controlling for group. This study indicate that MR patients show extensive damage in the integrity of the brain white matter tracts, and the right UF is an important neural basis of human intelligence.

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Activation of the human medial temporal lobes by stereoscopic depth cues.

Publication Date: 2008 May 1 PMID: 18353684
Authors: van Strien, N. M. - Scholte, H. S. - Witter, M. P.
Journal: Neuroimage

The perirhinal cortex (PER) is part of both the medial temporal lobe memory system (MTL) and the ventral visual stream (VVS). In the MTL, PER provides input to the hippocampal formation directly and via the entorhinal cortex (EC), whereas in the VVS, PER is considered to be at the top of the visual processing hierarchy of object information. Because of its position in both networks, PER presumably serves a role in memory and visual perception. PER's perceptual role is thought to be contingent upon the complexity of visual information, i.e., PER only becomes active in visual perception when many higher order visual cues are combined. Using high-resolution functional MRI (fMRI), we investigated the effect of varying the presence of binocular disparity, in complex visual object stimuli. Nineteen subjects were presented with movies of complex objects and a fixation cross, either with or without binocular disparity (referred to as stereo and mono condition respectively). Subjects were instructed to attentively watch the objects, but no instructions were given to memorize them. Group results showed increased activity in the MTL, among which is PER, when comparing the stereo over the mono condition (stereo > mono). Individual analysis showed dominant activation in the stereo > mono contrast in eleven out of nineteen subjects, whereas only three subjects showed dominance in the opposite contrast. We conclude that the MTL is differentially activated by the stereo and mono condition, such that activation is stronger when a complex visual object stimulus with disparity is presented.

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The molecular basis for gray and white matter contrast in phase imaging.

Publication Date: 2008 May 1 PMID: 18353683
Authors: Zhong, K. - Leupold, J. - von Elverfeldt, D. - Speck, O.
Journal: Neuroimage

Direct magnetic resonance phase images acquired at high field have been shown to yield superior gray and white matter contrast up to 10-fold higher compared to conventional magnitude images. However, the underlying contrast mechanism is not yet understood. This study demonstrates that the water resonance frequency is directly shifted by water-macromolecule exchange processes (0.040 ppm/mM for bovine serum albumin) and might be a major source of contribution to in vivo phase image contrast. Therefore, magnetic resonance phase imaging based on the proposed contrast mechanism could potentially be applied for in vivo studies of pathologies on a macromolecular level.

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Testing the validity of the TMS state-dependency approach: Targeting functionally distinct motion-selective neural populations in visual areas V1/V2 and V5/MT+.

Publication Date: 2008 May 1 PMID: 18353682
Authors: Silvanto, J. - Muggleton, N. G.
Journal: Neuroimage

By making use of the phenomenon that the effects of transcranial magnetic stimulation (TMS) are dependent on the initial cortical excitability, we show that TMS can reveal the properties of distinct neural populations within the stimulated region. Visual adaptation to either simple translational or radial motion was used to manipulate the initial activity state of neural populations of different tunings prior to application of TMS. After adaptation to either leftward or rightward motion, phosphenes induced from V1/V2 and the V5/MT+ complex took on the motion properties of the adapting stimulus, consistent with evidence that both regions contain direction-selective neurons. In contrast, after adaptation to radial motion, only phosphenes induced from the V5/MT+ complex took on the motion qualities of the adapting stimulus, consistent with findings that V5/MT+ but not V1/V2 contains neurons tuned to radial motion. That phosphenes induced from the V5/MT+ complex can appear containing either simple or radial motion demonstrates that the state dependency of TMS can be used to target specific neural populations within the affected region.

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Parallel input makes the brain run faster.

Publication Date: 2008 May 1 PMID: 18353681
Authors: Raij, T. - Karhu, J. - Kicic, D. - Lioumis, P. - Julkunen, P. - Lin, F. H. - Ahveninen, J. - Ilmoniemi, R. J. - Makela, J. P. - Hamalainen, M. - Rosen, B. R. - Belliveau, J. W.
Journal: Neuroimage

In serial sensory processing, information flows from the thalamus via primary sensory cortices to higher-order association areas. However, association cortices also receive, albeit weak, direct thalamocortical sensory inputs of unknown function. For example, while information proceeds from primary (SI) to secondary (SII) somatosensory cortex in a serial fashion, both areas are known to receive direct thalamocortical sensory input. The present study examines the potential roles of such parallel input arrangements. The subjects were presented with median nerve somatosensory stimuli with the instruction to respond with the contralateral hand. The locations and time courses of the activated brain areas were first identified with magnetoencephalography (MEG). In a subsequent session, these brain areas were modulated with single-pulse transcranial magnetic stimulation (TMS) at 15-210 ms after the somatosensory stimulus while electroencephalography (EEG) was recorded. TMS pulses at 15-40 ms post-stimulus significantly speeded up reaction times and somatosensory-evoked responses, with largest facilitatory effects when the TMS pulse was given to contralateral SII at about 20 ms. To explain the results, we propose that the early somatosensory-evoked physiological SII activation exerts an SII-->SI influence that facilitates the reciprocal SI-->SII pathway - with TMS to SII we apparently amplified this mechanism. The results suggest that the human brain may utilize parallel inputs to facilitate long-distance cortico-cortical connections, resulting in accelerated processing and speeded reaction times. This arrangement could also allow very early top-down modulation of the bottom-up stream of sensory information.

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A novel MR-compatible device for providing forces to the human finger during functional neuroimaging studies.

Publication Date: 2008 May 1 PMID: 18346913
Authors: Jackson, C. P. - Bowtell, R. - Morris, P. G. - Jackson, S. R.
Journal: Neuroimage

Many motor learning experiments involve subjects performing a task while experiencing external force perturbations. However, it is difficult to transfer these tasks to functional magnetic resonance imaging (fMRI) studies, and much of the technology that currently exists to facilitate this is expensive to produce and difficult to use. Here, we report on the design and construction of a novel device (the 'force coil') that is simple and inexpensive, and that uses the static magnetic field inside the scanner to provide forces to the human finger. The coil incorporates a potentiometer in the base to allow the recording of angular position. To test whether the magnetic field generated by the current flowing through the coil would interfere with the functional images collected, we compared images from a phantom during the use of the coil at arm's length in a 7T magnet. There was no noticeable interference from the coil at the levels of current used in this experiment, which produced about 10 N of force in a 7T scanner. In conclusion, the force coil is a cheap, easy to operate device which provides forces to the finger inside the scanner without affecting image quality. Designs based on this principle are likely to prove useful in studies of motor learning using fMRI.

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Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease.

Publication Date: 2008 May 1 PMID: 18343688
Authors: Habeck, C. - Foster, N. L. - Perneczky, R. - Kurz, A. - Alexopoulos, P. - Koeppe, R. A. - Drzezga, A. - Stern, Y.
Journal: Neuroimage

We performed univariate and multivariate discriminant analysis of FDG-PET scans to evaluate their ability to identify Alzheimer's disease (AD). FDG-PET scans came from two sources: 17 AD patients and 33 healthy elderly controls were scanned at the University of Michigan; 102 early AD patients and 20 healthy elderly controls were scanned at the Technical University of Munich, Germany. We selected a derivation sample of 20 AD patients and 20 healthy controls matched on age with the remainder divided into 5 replication samples. The sensitivity and specificity of diagnostic AD-markers and threshold criteria from the derivation sample were determined in the replication samples. Although both univariate and multivariate analyses produced markers with high classification accuracy in the derivation sample, the multivariate marker's diagnostic performance in the replication samples was superior. Further, supplementary analysis showed its performance to be unaffected by the loss of key regions. Multivariate measures of AD utilize the covariance structure of imaging data and provide complementary, clinically relevant information that may be superior to univariate measures.

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A bilateral cortico-bulbar network associated with breath holding in humans, determined by functional magnetic resonance imaging.

Publication Date: 2008 May 1 PMID: 18343687
Authors: McKay, L. C. - Adams, L. - Frackowiak, R. S. - Corfield, D. R.
Journal: Neuroimage

Few tasks are simpler to perform than a breath hold; however, the neural basis underlying this voluntary inhibitory behaviour, which must suppress spontaneous respiratory motor output, is unknown. Here, using blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI), we investigated the neural network responsible for volitional breath holding in 8 healthy humans. BOLD images of the whole brain (156 brain volumes, voxel resolution 3x3x3 mm) were acquired every 5.2 s. All breath holds were performed for 15 s at resting expiratory lung volume when respiratory musculature was presumed to be relaxed, which ensured that the protocol highlighted the inhibitory components underlying the breath hold. An experimental paradigm was designed to dissociate the time course of the whole-brain BOLD signal from the time course of the local, neural-related BOLD signal associated with the inhibitory task. We identified a bilateral network of cortical and subcortical structures including the insula, basal ganglia, frontal cortex, parietal cortex and thalamus, which are in common with response inhibition tasks, and in addition, activity within the pons. From these results we speculate that the pons has a role in integrating information from supra-brainstem structures, and in turn it exerts an inhibitory effect on medullary respiratory neurones to inhibit breathing during breath holding.

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The neural mechanism underlying the female advantage in identifying negative emotions: An event-related potential study.

Publication Date: 2008 May 1 PMID: 18343686
Authors: Li, H. - Yuan, J. - Lin, C.
Journal: Neuroimage

Previous studies have extensively reported an advantage of females in identifying negative facial emotions as compared with males. Nevertheless, why females are better in performance relative to males during emotion recognition tasks is still unknown, and the neural mechanism(s) underlying this phenomenon has yet to be directly investigated. As facial affects convey emotional information which is adaptively important and the recognition of a given facial affect generally evokes individuals' emotion of the same type [Dimberg, U., 1997. Facial reactions: rapidly evoked emotional responses. J. Psychophysiol. 11, 115-123], the present study assumes that the female advantage in emotion recognition may result from the attenuated sensitivity of males to emotionally negative stimuli of lesser valence intensity compared to that of females. In contrast, each gender may be comparably sensitive to emotionally negative stimuli of enhanced salience as suggested by the emotional negativity bias. To test this hypothesis, event-related potentials were recorded for highly negative (HN), moderately negative (MN), and Neutral deviant images while subjects (15 males, 15 females) perform a standard/deviant categorization task, irrespective of the emotional valence of deviants. The results demonstrated more negative ERP deflections during HN condition than during MN and Neutral conditions at early N2 and later P3 components, irrespective of gender. Moreover, MN condition elicited significantly more negative deflections than the Neutral condition across N2 and P3 components only in females, and the MN-Neutral difference waveform in females during 250-450 ms interval was localized to the right prefrontal cortex. Thus, apart from the increased sensitivity of both genders to the highly negative stimuli, the present study demonstrated that women, instead of men, are sensitive to emotionally negative stimuli of lesser saliency, which may be an important mechanism underlying the female advantage in identifying negative emotions, and the right prefrontal cortex may be the neural basis underlying the female-specific sensitivity to emotionally negative stimuli of lesser salience.

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Experience-dependent neural substrates involved in vocal pitch regulation during singing.

Publication Date: 2008 May 1 PMID: 18343163
Authors: Zarate, J. M. - Zatorre, R. J.
Journal: Neuroimage

Proper singing requires the integration of auditory feedback mechanisms with the vocal motor system, such that vocal pitch can be precisely controlled. To determine the neural substrates involved in audio-vocal integration, non-musicians and experienced singers underwent fMRI scanning while they sang a single tone with either unaltered ("simple") or pitch-shifted auditory feedback; in pitch-shifted trials, subjects were instructed either to ignore or compensate for the shifted feedback. We hypothesized that the anterior cingulate cortex (ACC), superior temporal gyrus (STG), and anterior insula may be involved in audio-vocal integration due to their functional roles during singing and their anatomical connectivity. Although singers were more accurate than non-musicians in simple singing, both groups recruited similar functional networks. Singers ignored the shifted feedback better than non-musicians, and both groups also displayed different patterns of neural activity for this task: singers recruited bilateral auditory areas and left putamen, while non-musicians recruited the left supramarginal gyrus and primary motor cortex. While there were no significant group differences in performing the compensate task, singers displayed enhanced activity in the ACC, superior temporal sulcus, and putamen, whereas non-musicians exhibited increased activity in the dorsal premotor cortex, a region involved with sensorimotor interactions. We propose two neural substrates for audio-vocal integration: the dorsal premotor cortex may act as a basic interface, but with vocal training and practice, the ACC, auditory cortices, and putamen may be increasingly recruited as people learn to monitor their auditory feedback and adjust their vocal output accordingly.

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The micro-architecture of the cerebral cortex: Functional neuroimaging models and metabolism.

Publication Date: 2008 May 1 PMID: 18343162
Authors: Riera, J. J. - Schousboe, A. - Waagepetersen, H. S. - Howarth, C. - Hyder, F.
Journal: Neuroimage

In order to interpret/integrate data obtained with different functional neuroimaging modalities (e.g. fMRI, EEG/MEG, PET/SPECT, fNIRS), forward-generative models of a diversity of brain mechanisms at the mesoscopic level are considered necessary. For the cerebral cortex, the brain structure with possibly the most relevance for functional neuroimaging, a variety of such biophysical models has been proposed over the last decade. The development of technological tools to investigate in vitro the physiological, anatomical and biochemical principles at the microscopic scale in comparative studies formed the basis for such theoretical progresses. However, with the most recent introduction of systems to record electrical (e.g. miniaturized probes chronically/acutely implantable in the brain), optical (e.g. two-photon laser scanning microscopy) and atomic nuclear spectral (e.g. nuclear magnetic resonance spectroscopy) signals using living laboratory animals, the field is receiving even greater attention. Major advances have been achieved by combining such sophisticated recording systems with new experimental strategies (e.g. transgenic/knock-out animals, high resolution stereotaxic manipulation systems for probe-guidance and cellular-scale chemical-delivery). Theoreticians may now be encouraged to re-consider previously formulated mesoscopic level models in order to incorporate important findings recently made at the microscopic scale. In this series of reviews, we summarize the background at the microscopic scale, which we suggest will constitute the foundations for upcoming representations at the mesoscopic level. In this first part, we focus our attention on the nerve ending particles in order to summarize basic principles and mechanisms underlying cellular metabolism in the cerebral cortex. It will be followed by two parts highlighting major features in its organization/working-principles to regulate both cerebral blood circulation and neuronal activity, respectively. Contemporary theoretical models for functional neuroimaging will be revised in the fourth part, with particular emphasis in their applications, advantages/limitations and future prospects.

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Differential sensitivity for viewpoint between familiar and unfamiliar faces in human visual cortex.

Publication Date: 2008 May 1 PMID: 18343161
Authors: Ewbank, M. P. - Andrews, T. J.
Journal: Neuroimage

People are extremely proficient at recognizing faces that are familiar to them, but are poor at identifying unfamiliar faces. We used fMR-adaptation to ask whether this difference in recognition might be reflected in the relative viewpoint-dependence of face-selective regions in the brain. A reduced response (adaptation) to repeated images of unfamiliar or familiar faces was found in the fusiform face area (FFA), but not in the superior temporal sulcus (STS) face-selective region. To establish if the neural representation of faces was invariant to changes in viewpoint, we parametrically varied the viewing angle of successive images using 3-dimensional models of unfamiliar and familiar faces. We found adaptation to familiar faces across all changes in viewpoint in the FFA. In contrast, a release from adaptation was apparent in the FFA when unfamiliar faces were viewed at increasing viewing angles. These results provide a neural basis for differences in the recognition of familiar and unfamiliar faces.

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Hypothermia effects on neurovascular coupling and cerebral metabolic rate of oxygen.

Publication Date: 2008 May 1 PMID: 18343160
Authors: Royl, G. - Fuchtemeier, M. - Leithner, C. - Megow, D. - Offenhauser, N. - Steinbrink, J. - Kohl-Bareis, M. - Dirnagl, U. - Lindauer, U.
Journal: Neuroimage

Neuronal activation is accompanied by a local increase in cerebral blood flow (CBF) and in cerebral metabolic rate of oxygen (CMRO(2)), caused by neurovascular and neurometabolic coupling. Hypothermia is used as a neuroprotective approach in surgical patients and therapeutically after cardiac arrest or stroke. The effect of hypothermia on neurovascular coupling is of interest for evaluating brain function in these patients, but has not been determined so far. It is not clear whether functional hyperaemia actually operates at subnormal temperatures. In addition, decreasing brain temperature reduces spontaneous CMRO(2) following a known quantitative relationship (Q(10)). Q(10) determination may serve to validate a recently introduced CMRO(2) measurement approach relying on optical measurements of CBF and hemoglobin concentration. We applied this method to investigate hypothermia in a functional study of the somatosensory cortex. Anesthetized Wistar rats underwent surgical implantation of a closed cranial window. Using laser Doppler flowmetry and optical spectroscopy, relative changes in CBF and hemoglobin concentration were measured continuously. At the same time, an electroencephalogram (EEG) was recorded from the measurement site. By the application of ice packs, whole-body hypothermia was induced, followed by rewarming. Spontaneous EEG, CBF and CMRO(2) were measured, interleaved by blocks of electrical forepaw stimulation. The Q(10) obtained from spontaneous CMRO(2) changes of 4.4 (95% confidence interval 3.7-5.1) was close to published values, indicating the reliability of the CMRO(2) measurement. Lowering brain temperature decreased functional changes of CBF and CMRO(2) as well as amplitudes of somatosensory evoked potentials (SEP) to the same degree. In conclusion, neurovascular and neurometabolic coupling is preserved during hypothermia.

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Detection and scaling of task-induced fMRI-BOLD response using resting state fluctuations.

Publication Date: 2008 May 1 PMID: 18343159
Authors: Kannurpatti, S. S. - Biswal, B. B.
Journal: Neuroimage

This study evaluated a calibration technique for scaling the fMRI-BOLD response during a simple motor task. A novel scaling parameter, resting state physiological fluctuation amplitude (RSFA), was tested using previously established scaling factors such as breath hold or 5% CO(2). RSFA was hypothesized to contain vascular reactivity information present in the resting state fMRI signal. Subjects were scanned under various stimulus conditions: (a) rest while breathing room air, (b) bilateral fingertapping, (c) breath holding and (d) moderate hypercapnia (breathing 5% CO(2)+air). In all subjects who breathed 5% CO(2), RSFA correlated highly with the BOLD response amplitude during 5% CO(2) inhalation. Also, RSFA correlated highly with the amplitude of the BOLD response elicited by breath hold. RSFA was therefore used as a hemodynamic scaling factor to calibrate both the amplitude and spatial extent of the fMRI-BOLD response during the motor task (fingertapping). Results revealed that amplitude scaling using RSFA was similar to that using breath hold or 5% CO(2), where the spatial extent of activation diminished by 20-37% over all subjects. Spatial extent of activation changed significantly after scaling and only 30-40% of the activated area overlapped with the unscaled activation. RSFA-scaled task-induced fMRI-BOLD response in both amplitude and spatial extent was comparable to that obtained using breath hold or 5% CO(2). We conclude that RSFA may be used to hemodynamically scale the fMRI-BOLD response and does not require the use of a hypercapnic challenge (which may not be purely non-neural), which can be difficult to implement in special populations.

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The neural basis of belief encoding and integration in moral judgment.

Publication Date: 2008 May 1 PMID: 18342544
Authors: Young, L. - Saxe, R.
Journal: Neuroimage

Moral judgment in the mature state depends on "theory of mind", or the capacity to attribute mental states (e.g., beliefs, desires, and intentions) to moral agents. The current study uses functional magnetic resonance imaging (fMRI) to investigate the cognitive processes for belief attribution in moral judgment. Participants read vignettes in a 2x2x2 design: protagonists produced either a negative or neutral outcome, based on the belief that they were causing the negative outcome or the neutral outcome; presentation of belief information either preceded or followed outcome information. In each case, participants judged the moral permissibility of the action. The results indicate that while the medial prefrontal cortex is recruited for processing belief valence, the temporo-parietal junction and precuneus are recruited for processing beliefs in moral judgment via two distinct component processes: (1) encoding beliefs and (2) integrating beliefs with other relevant features of the action (e.g., the outcome) for moral judgment.

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Impact of inconsistent resolution on VBM studies.

Publication Date: 2008 May 1 PMID: 18342543
Authors: Pereira, J. M. - Nestor, P. J. - Williams, G. B.
Journal: Neuroimage

This paper considers the effects of using magnetic resonance scans with different voxel dimensions in voxel-based morphometry studies. This is of potential relevance to many longitudinal studies or any ad-hoc study that relies on pre-existing databases of subjects. In order to study this effect, a group of controls were contrasted with a group of semantic dementia as well as with a group of Alzheimer's disease patients using a mixture of different voxel dimensions scans on each side of the statistical test. Scans were interpolated using a sinc function in order to obtain a different voxel depth. The effects were measured by comparing the output of each analysis to the benchmark in which all scans had the original depth (and highest resolution), both visually and through the computation of the root-mean-square error difference between the resulting t-maps. It was shown that the impact is highly dependent on the scan itself, with some images showing more robustness to the interpolation process, and hence yielding fewer differences. A measure of robustness is proposed, which may be used in order to understand the impact of mixing different dimensions or adjusting them for each scan. Indiscriminate use of voxel dimensions on both groups was found to produce more errors (false positives/false negatives) than does an approach involving the use of balanced groups and a voxel dimension nuisance covariate.

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Classification images reveal the information sensitivity of brain voxels in fMRI.

Publication Date: 2008 May 1 PMID: 18342542
Authors: Smith, F. W. - Muckli, L. - Brennan, D. - Pernet, C. - Smith, M. L. - Belin, P. - Gosselin, F. - Hadley, D. M. - Cavanagh, J. - Schyns, P. G.
Journal: Neuroimage

Reverse correlation methods have been widely used in neuroscience for many years and have recently been applied to study the sensitivity of human brain signals (EEG, MEG) to complex visual stimuli. Here we employ one such method, Bubbles (Gosselin, F., Schyns, P.G., 2001. Bubbles: A technique to reveal the use of information in recognition tasks. Vis. Res. 41, 2261-2271), in conjunction with fMRI in the context of a 3AFC facial expression categorization task. We highlight the regions of the brain showing significant sensitivity with respect to the critical visual information required to perform the categorization judgments. Moreover, we reveal the actual subset of visual information which modulates BOLD sensitivity within each such brain region. Finally, we show the potential which lies within analyzing brain function in terms of the information states of different brain regions. Thus, we can now analyse human brain function in terms of the specific visual information different brain regions process.

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Indirect measurement of regional axon diameter in excised mouse spinal cord with q-space imaging: Simulation and experimental studies.

Publication Date: 2008 May 1 PMID: 18342541
Authors: Ong, H. H. - Wright, A. C. - Wehrli, S. L. - Souza, A. - Schwartz, E. D. - Hwang, S. N. - Wehrli, F. W.
Journal: Neuroimage

Q-space imaging (QSI), a diffusion MRI technique, can provide quantitative tissue architecture information at cellular dimensions not amenable by conventional diffusion MRI. By exploiting regularities in molecular diffusion barriers, QSI can estimate the average barrier spacing such as the mean axon diameter in white matter (WM). In this work, we performed ex vivo QSI on cervical spinal cord sections from healthy C57BL/6 mice at 400 MHz using a custom-designed uniaxial 50T/m gradient probe delivering a 0.6 mum displacement resolution capable of measuring axon diameters on the scale of 1 mum. After generating QSI-derived axon diameter maps, diameters were calculated using histology from seven WM tracts (dorsal corticospinal, gracilis, cuneatus, rubrospinal, spinothalamic, reticulospinal, and vestibulospinal tracts) each with different axon diameters. We found QSI-derived diameters from regions drawn in the seven WM tracts (1.1 to 2.1 mum) to be highly correlated (r(2)=0.95) with those calculated from histology (0.8 to 1.8 mum). The QSI-derived values overestimated those obtained by histology by approximately 20%, which is likely due to the presence of extra-cellular signal. Finally, simulations on images of synthetic circular axons and axons from histology suggest that QSI-derived diameters are informative despite diameter and axon shape variation and the presence of intra-cellular and extra-cellular signal. QSI may be able to quantify nondestructively changes in WM axon architecture due to pathology or injury at the cellular level.

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The cortical motor threshold reflects microstructural properties of cerebral white matter.

Publication Date: 2008 May 1 PMID: 18342540
Authors: Kloppel, S. - Baumer, T. - Kroeger, J. - Koch, M. A. - Buchel, C. - Munchau, A. - Siebner, H. R.
Journal: Neuroimage

Transcranial magnetic stimulation (TMS) can be used to probe distinct aspects of excitability of the primary motor hand area (M1(Hand)). The motor threshold (MT) reflects the trans-synaptic excitability of corticospinal output neurons. The MT corresponds to the minimal intensity at which TMS evokes a contralateral motor response. Here, we employed diffusion-weighted imaging (DWI) to examine whether inter-individual differences in MT of the left and right M1(Hand), an index of cortical excitability, are associated with variations in fractional anisotropy (FA), an index of white matter microstructure. Resting and active MT showed an inverse linear relationship with regional FA values in large bihemispheric clusters, including the white matter underlying primary motor, premotor and posterior prefrontal cortices, as well as the genu of the internal capsule, cerebral peduncles and corpus callosum. The linear increase in FA with cortical excitability as indexed by the MT remained significant after controlling for differences in handedness or coil-cortex distance. The posterior limb of the internal capsule, where fast-conducting corticospinal fibres from M1(Hand) pass through, showed only a weak linear relationship between FA and MT. The FA measurements show that a high level of corticospinal excitability is associated with a higher fibre coherence in large parts of cerebral white matter. The higher FA values in the white matter beneath premotor and motor cortices may reflect a structural property of cortico-cortical connections that renders M1(Hand) more susceptible to TMS-induced trans-synaptic excitation of the corticospinal fibres and may account for the inverse linear relationship between MT and FA.

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Analysis of laminar activity in normal and injured rat spinal cord by manganese enhanced MRI.

Publication Date: 2008 May 1 PMID: 18339560
Authors: Bonny, J. M. - Mailly, P. - Renou, J. P. - Orsal, D. - Benmoussa, A. - Stettler, O.
Journal: Neuroimage

The present study provides an account of a sensitive and rapid experimental approach for MRI visualization and analysis of spinal cord (SC) laminar activity in normal and injured animals. This approach is based upon neuronal activity-dependant manganese (Mn) uptake after focal SC injection of MnCl(2), and subsequent ex-vivo magnetic resonance imaging (MRI) of activated SC pathways. The method was designed as an alternative to time-intensive histochemical and behavioral approaches typically used for analysis of spinal cord injury (SCI) and our results provide both anatomical and functional insights. We show that ex vivo imaging can determine layer-specific activity over an extended region of the rat SC. In addition, we demonstrate that the Mn concentration profile along the SC axis accurately reflects the type of SC injury. The approach is flexible since MRI analysis can be done immediately after animal sacrifice, or alternatively several days later, without a loss of sensitivity. Moreover, the integrity and functional state of SC circuitry can be analyzed in less than 1 h whereas several days and weeks are necessary to perform classical histochemical and behavioral analysis. Thus our method can be used for precise assessment of the extent of dysfunction or change in SC disorders and may facilitate the screening of molecules with therapeutic potential after SC injury.

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Spatio-temporal characteristics of low-frequency BOLD signal fluctuations in isoflurane-anesthetized rat brain.

Publication Date: 2008 May 1 PMID: 18339559
Authors: Kannurpatti, S. S. - Biswal, B. B. - Kim, Y. R. - Rosen, B. R.
Journal: Neuroimage

We studied the spatio-temporal characteristics of the resting state low-frequency fluctuations in fMRI-BOLD signal in isoflurane-anesthetized rats. fMRI-BOLD measurements at 9.4 T were made during normal and exsanguinated condition previously known to alter cerebral blood flow (CBF) fluctuations in anesthetized rats. fMRI signal time series were low pass filtered and studied by spectral analysis. During normal conditions, baseline mean arterial pressure (MAP) was 110+/-10 mm Hg and low-frequency fluctuations in BOLD signal were observed in the frequency range of 0.01 to 0.125 Hz. Following blood withdrawal (exsanguination), MAP decreased to 68+/-7 mm Hg, resulting in an increase in the amplitude of the low-frequency fluctuations in BOLD signal time series and an increase in power at several frequencies between 0.01 and 0.125 Hz. Spatially, the BOLD fluctuations were confined to the cortex and thalamus spanning both hemispheres with sparse presence in the caudate putamen and hippocampus during both normal and exsanguinated states. Spatial distribution of the low-frequency fluctuations in BOLD signal, from cross-correlation analysis, indicates substantial inter-hemispheric synchrony similar to that observed in the conscious human brain. The behavior of the resting state BOLD signal fluctuations similar to CBF fluctuations during exsanguination indicates a myogenic dependence. Also, a high inter-hemispheric synchrony combined with different phase characteristics of the low-frequency BOLD fluctuations particularly in the hippocampus relative to the cortex emphasizes distinct functional networks.

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Spatiotemporal frequency tuning of BOLD and gamma band MEG responses compared in primary visual cortex.

Publication Date: 2008 May 1 PMID: 18337125
Authors: Muthukumaraswamy, S. D. - Singh, K. D.
Journal: Neuroimage

In this study, the spatial and temporal frequency tuning characteristics of the MEG gamma (40-60 Hz) rhythm and the BOLD response in primary visual cortex were measured and compared. In an identical MEG/fMRI paradigm, 10 participants viewed reversing square wave gratings at 2 spatial frequencies [0.5 and 3 cycles per degree (cpd)] reversing at 5 temporal frequencies (0, 1 6, 10, 15 Hz). Three-dimensional images of MEG source power were generated with synthetic aperture magnetometry (SAM) and showed a high degree of spatial correspondence with BOLD responses in primary visual cortex with a mean spatial separation of 6.5 mm, but the two modalities showed different tuning characteristics. The gamma rhythm showed a clear increase in induced power for the high spatial frequency stimulus while BOLD showed no difference in activity for the two spatial frequencies used. Both imaging modalities showed a general increase of activity with temporal frequency, however, BOLD plateaued around 6-10 Hz while the MEG generally increased with a dip exhibited at 6 Hz. These results demonstrate that the two modalities may show activation in similar spatial locations but that the functional pattern of these activations may differ in a complex manner, suggesting that they may be tuned to different aspects of neuronal activity.

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Neocortical reorganization in spina bifida.

Publication Date: 2008 May 1 PMID: 18337124
Authors: Juranek, J. - Fletcher, J. M. - Hasan, K. M. - Breier, J. I. - Cirino, P. T. - Pazo-Alvarez, P. - Diaz, J. D. - Ewing-Cobbs, L. - Dennis, M. - Papanicolaou, A. C.
Journal: Neuroimage

Normal brain development throughout childhood and adolescence is usually characterized by decreased cortical thickness in the frontal regions as well as region-specific patterns of increased white matter myelination and volume. We investigated total cerebral volumes, neocortical surface area, and neocortical thickness in 16 children with a neural tube defect, spina bifida myelomeningocele (SB), and 16 age-matched typically developing controls using a semi-automated, quantitative approach to MRI-based brain morphometry. The results revealed no significant group differences in total cerebral volume. However, group differences were observed in the global distribution of distinct tissue classes within the cerebrum: the SB group demonstrated a significant 15% reduction in total white matter and a 69% increase in cerebrospinal fluid, with no differences in total gray matter. Group comparisons of neocortical surface area assessments were significantly smaller in the occipital regions for SB, with no significant group differences in the frontal regions. Group comparisons of cortical thickness measurements demonstrated reduced cortical thickness in all regions except the frontal regions, where the SB group exhibited an increase relative to the PC group. Although regional patterns of thinning may be associated with the mechanical effects of hydrocephalus, the overall reduction in white matter and increased neocortical thickness in the frontal regions suggest that SB reflects a long-term disruption of brain development that extends far beyond the neural tube defect in the first weeks of gestation.

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Distinguishing specific sexual and general emotional effects in fMRI-Subcortical and cortical arousal during erotic picture viewing.

Publication Date: 2008 May 1 PMID: 18329905
Authors: Walter, M. - Bermpohl, F. - Mouras, H. - Schiltz, K. - Tempelmann, C. - Rotte, M. - Heinze, H. J. - Bogerts, B. - Northoff, G.
Journal: Neuroimage

Sexual activity involves excitement with high arousal and pleasure as typical features of emotions. Brain activations specifically related to erotic feelings and those related to general emotional processing are therefore hard to disentangle. Using fMRI in 21 healthy subjects (11 males and 10 females), we investigated regions that show activations specifically related to the viewing of sexually intense pictures while controlling for general emotional arousal (GEA) or pleasure. Activations in the ventral striatum and hypothalamus were found to be modulated by the stimulus' specific sexual intensity (SSI) while activations in the anterior cingulate cortex were associated with an interaction between sexual intensity and emotional valence. In contrast, activation in other regions like the dorsomedial prefrontal cortex, the mediodorsal thalamus and the amygdala was associated only with a general emotional component during sexual arousal. No differences were found in these effects when comparing females and males. Our findings demonstrate for the first time neural differentiation between emotional and sexual components in the neural network underlying sexual arousal.

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Neural correlates of age-related changes in cortical neurophysiology.

Publication Date: 2008 May 1 PMID: 18329904
Authors: Talelli, P. - Ewas, A. - Waddingham, W. - Rothwell, J. C. - Ward, N. S.
Journal: Neuroimage

Functional imaging studies of cortical motor systems in humans have demonstrated age-related reorganisation often attributed to anatomical and physiological changes. In this study we investigated whether aspects of brain activity during a motor task were influenced not only by age, but also by neurophysiological parameters of the motor cortex contralateral to the moving hand. Twenty seven right-handed volunteers underwent functional magnetic resonance imaging whilst performing repetitive isometric right hand grips in which the target force was parametrically varied between 15 and 55% of each subject's own maximum grip force. For each subject we characterised two orthogonal parameters, B(G) (average task-related activity for all hand grips) and B(F) (the degree to which task-related activity co-varied with peak grip force). We used transcranial magnetic stimulation (TMS) to assess task-related changes in interhemispheric inhibition from left to right motor cortex (IHIc) and to perform measures relating to left motor cortex excitability during activation of the right hand. Firstly, we found that B(G) in right (ipsilateral) motor cortex was greater with increasing values of age(2) and IHIc. Secondly, B(F) in left ventral premotor cortex was greater in older subjects and in those in whom contralateral M1 was less responsive to TMS stimulation. In both cases, neurophysiological parameters accounted for variability in brain responses over and above that explained by ageing. These results indicate that neurophysiological markers may be better indicators of biological ageing than chronological age and point towards the mechanisms by which reconfiguration of distributed brain networks occurs in the face of degenerative changes.

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Human secondary somatosensory cortex is involved in the processing of somatosensory rare stimuli: An fMRI study.

Publication Date: 2008 May 1 PMID: 18329293
Authors: Chen, T. L. - Babiloni, C. - Ferretti, A. - Perrucci, M. G. - Romani, G. L. - Rossini, P. M. - Tartaro, A. - Del Gratta, C.
Journal: Neuroimage

In the human somatosensory system, the contralateral primary somatosensory cortex (SI) is presumed to process and encode type and intensity of the sensory inputs, whereas the bilateral secondary somatosensory cortex (SII) is believed to perform higher order functions including sensorimotor integration, integration of information from the two body halves, attention, learning and memory. In this fMRI study we investigated the effect of attention on the activation of SI and SII, as induced by nonpainful and painful rare deviant electric stimuli during somatosensory oddball tasks. The working hypothesis is of stronger effects of attention on SII with respect to SI. Four runs were acquired according to an oddball scheme. Frequent nonpainful electrical stimuli were delivered to the ulnar nerve at motor threshold, whereas rare/deviant stimuli were delivered to median nerve in four conditions (one condition per run): nonpainful, painful, counting nonpainful, and counting painful. Results showed a statistically significant fMRI activation in bilateral SII but not in contralateral SI when the rare/deviant median nerve stimuli were delivered at nonpainful and painful levels as well as at the two levels of attention considered (i.e., associated with counting and non-counting tasks). Furthermore, fMRI activation in SII did not differ across the different levels of stimulus intensity (nonpainful, painful) and attention (non-counting, counting). These results corroborate the notion that SII is the target of independent pathways for the processing and integration of nonpainful and painful somatosensory stimuli salient for further high-order elaborations.

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The impact of temporal regularization on estimates of the BOLD hemodynamic response function: A comparative analysis.

Publication Date: 2008 May 1 PMID: 18329292
Authors: Casanova, R. - Ryali, S. - Serences, J. - Yang, L. - Kraft, R. - Laurienti, P. J. - Maldjian, J. A.
Journal: Neuroimage

In fMRI data analysis it has been shown that for a wide range of situations the hemodynamic response function (HRF) can be reasonably characterized as the impulse response function of a linear and time invariant system. An accurate and robust extraction of the HRF is essential to infer quantitative information about the relative timing of the neuronal events in different brain regions. When no assumptions are made about the HRF shape, it is most commonly estimated using time windowed averaging or a least squares estimated general linear model based on either Fourier or delta basis functions. Recently, regularization methods have been employed to increase the estimation efficiency of the HRF; typically these methods produce more accurate HRF estimates than the least squares approach [Goutte, C., Nielsen, F.A., Hansen, L.K., 2000. Modeling the Haemodynamic Response in fMRI Using Smooth FIR Filters. IEEE Trans. Med. Imag. 19(12), 1188-1201.]. Here, we use simulations to clarify the relative merit of temporal regularization based methods compared to the least squares methods with respect to the accuracy of estimating certain characteristics of the HRF such as time to peak (TTP), height (HR) and width (W) of the response. We implemented a Bayesian approach proposed by Marrelec et al. [Marrelec, G., Benali, H., Ciuciu, P., Pelegrini-Issac, M., Poline, J.-B., 2003. Robust Estimation of the Hemodynamic Response Function in Event-Related BOLD fMRI Using Basic Physiological Information. Hum. Brain Mapp. 19, 1-17., Marrelec, G., Benali, H., Ciuciu, P., Poline, J.B. Bayesian estimation of the hemodynamic of the hemodynamic response function in functional MRI. In: R. F, editor; 2001; Melville. p 229-247.] and its deterministic counterpart based on a combination of Tikhonov regularization [Tikhonov, A.N., Arsenin, V.Y., 1977. Solution of ill-posed problems. Washington DC: W.H. Winston.] and generalized cross-validation (GCV) [Wahba, G., 1990. Spline Models for Observational Data. Philadelphia: SIAM.] for selecting the regularization parameter. The performance of both methods is compared with least square estimates as a function of temporal resolution, color and strength of the noise, and the type of stimulus sequences used. In almost all situations, under the considered assumptions (e.g. linearity, time invariance and smooth HRF), the regularization-based techniques more accurately characterize the HRF compared to the least-squares method. Our results clarify the effects of temporal resolution, noise color, and experimental design on the accuracy of HRF estimation.

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Calibrated fMRI in the medial temporal lobe during a memory-encoding task.

Publication Date: 2008 May 1 PMID: 18329291
Authors: Restom, K. - Perthen, J. E. - Liu, T. T.
Journal: Neuroimage

Prior measures of the blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF) responses to a memory-encoding task within the medial temporal lobe have suggested that the coupling between functional changes in CBF and changes in the cerebral metabolic rate of oxygen (CMRO(2)) may be tighter in the medial temporal lobe as compared to the primary sensory areas. In this study, we used a calibrated functional magnetic resonance imaging (fMRI) approach to directly estimate memory-encoding-related changes in CMRO(2) and to assess the coupling between CBF and CMRO(2) in the medial temporal lobe. The CBF-CMRO(2) coupling ratio was estimated using a linear fit to the flow and metabolism changes observed across subjects. In addition, we examined the effect of region-of-interest (ROI) selection on the estimates. In response to the memory-encoding task, CMRO(2) increased by 23.1+/-8.8% to 25.3+/-5.7% (depending upon ROI), with an estimated CBF-CMRO(2) coupling ratio of 1.66+/-0.07 to 1.75+/-0.16. There was not a significant effect of ROI selection on either the CMRO(2) or coupling ratio estimates. The observed coupling ratios were significantly lower than the values (2 to 4.5) that have been reported in previous calibrated fMRI studies of the visual and motor cortices. In addition, the estimated coupling ratio was found to be less sensitive to the calibration procedure for functional responses in the medial temporal lobe as compared to the primary sensory areas.

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Effective connectivity during haptic perception: A study using Granger causality analysis of functional magnetic resonance imaging data.

Publication Date: 2008 May 1 PMID: 18329290
Authors: Deshpande, G. - Hu, X. - Stilla, R. - Sathian, K.
Journal: Neuroimage

Although it is accepted that visual cortical areas are recruited during touch, it remains uncertain whether this depends on top-down inputs mediating visual imagery or engagement of modality-independent representations by bottom-up somatosensory inputs. Here we addressed this by examining effective connectivity in humans during haptic perception of shape and texture with the right hand. Multivariate Granger causality analysis of functional magnetic resonance imaging (fMRI) data was conducted on a network of regions that were shape- or texture-selective. A novel network reduction procedure was employed to eliminate connections that did not contribute significantly to overall connectivity. Effective connectivity during haptic perception was found to involve a variety of interactions between areas generally regarded as somatosensory, multisensory, visual and motor, emphasizing flexible cooperation between different brain regions rather than rigid functional separation. The left postcentral sulcus (PCS), left precentral gyrus and right posterior insula were important sources of connections in the network. Bottom-up somatosensory inputs from the left PCS and right posterior insula fed into visual cortical areas, both the shape-selective right lateral occipital complex (LOC) and the texture-selective right medial occipital cortex (probable V2). In addition, top-down inputs from left postero-supero-medial parietal cortex influenced the right LOC. Thus, there is strong evidence for the bottom-up somatosensory inputs predicted by models of visual cortical areas as multisensory processors and suggestive evidence for top-down parietal (but not prefrontal) inputs that could mediate visual imagery. This is consistent with modality-independent representations accessible through both bottom-up sensory inputs and top-down processes such as visual imagery.

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Motor learning transiently changes cortical somatotopy.

Publication Date: 2008 May 1 PMID: 18329289
Authors: Molina-Luna, K. - Hertler, B. - Buitrago, M. M. - Luft, A. R.
Journal: Neuroimage

Learning a complex motor skill is associated with changes in motor cortex representations of trained body parts. It has been suggested that representation changes reflect the storage of a skill, i.e., the motor memory trace. If a reflection of the trace, such modifications should persist after training is stopped for as long as the skill is retained. The objective here was to test the persistence of learning-related changes in the representation of the forelimb of the rat after learning a reaching task using repeated epidural stimulation mapping of primary motor cortex. It is shown that the forelimb representations enlarge after 8 days of training (n=8) but contract while performing arm movements without learning (n=7, p=0.006); hindlimb representations remain unchanged. Enlargement correlated with learning success (r=0.82; p=0.012). Subsequently, after 8 days without training, representation size reverted to baseline while the motor skill was retained. Somatotopy remained unaltered by a second training phase in which performance did not improve further (n=5). These findings suggest that successful acquisition but not storage of a motor skill depends on cortical map changes. The motor memory trace in rats may require changes in motor cortex organization other than those detected by stimulation mapping.

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Voxelwise Bayesian lesion-deficit analysis.

Publication Date: 2008 May 1 PMID: 18328733
Authors: Chen, R. - Hillis, A. E. - Pawlak, M. - Herskovits, E. H.
Journal: Neuroimage

Relating cognitive deficits to the presence of lesions has been an important means of delineating structure-function associations in the human brain. We propose a voxel-based Bayesian method for lesion-deficit analysis, which identifies complex linear or nonlinear associations among brain-lesion locations, and neurological status. We validated this method using a simulated data set, and we applied this algorithm to data obtained from an acute-stroke study to identify associations among voxels with infarct or hypoperfusion, and impaired word reading. We found that a distributed region involving Brodmann areas (BA) 22, 37, 39, and 40 was implicated in word reading.

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Manganese enhanced MRI detects mossy fiber sprouting rather than neurodegeneration, gliosis or seizure-activity in the epileptic rat hippocampus.

Publication Date: 2008 May 1 PMID: 18328732
Authors: Immonen, R. J. - Kharatishvili, I. - Sierra, A. - Einula, C. - Pitkanen, A. - Grohn, O. H.
Journal: Neuroimage

We tested a hypothesis that manganese enhanced magnetic resonance imaging (MEMRI) after systemic injection of MnCl(2) could detect axonal sprouting in the hippocampus following kainate (KA) induced status epilepticus (SE). MEMRI was performed at 3 h, 25 h, 4 days, and 2 months post-SE. To assess the contribution of various cellular alterations that occur in parallel with sprouting to the MEMRI signal, we sacrificed animals for histology at 4 days and 2 months post-SE. Neurodegeneration was assessed from thionin and Fluoro-Jade B stained preparations, astrogliosis from GFAP (glial fibrillary acidic protein) and microgliosis from Ox-42 immunostained preparations. Sprouting of granule cells axons (mossy fibers) in the dentate gyrus was analyzed from Timm stained sections. Occurrence of spontaneous epileptic seizures was analyzed at 2 months post-SE using continuous video-EEG monitoring. Integrity of the blood-brain barrier (BBB) was studied using Gd-enhanced MRI. We found abnormal MEMRI hyperintensity in the CA1 and the dentate gyrus at 2 months post-SE but not at earlier time points. Based on histologic analysis of individual animals with MEMRI hyperintensity, hippocampal MEMRI changes could be attributed to increasing axonal density rather than to neurodegeneration, astrogliosis, or microgliosis. Moreover, MEMRI contrast was not affected by seizure activity, and we could not detect any leakage of the BBB that could have explained the observed MEMRI hyperintensity. Present data show that systemic MEMRI can reveal axonal sprouting, and thus, can potentially serve as a marker for neuroplasticity in preclinical studies.

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Voxel-based cortical thickness measurements in MRI.

Publication Date: 2008 May 1 PMID: 18325790
Authors: Hutton, C. - De Vita, E. - Ashburner, J. - Deichmann, R. - Turner, R.
Journal: Neuroimage

The thickness of the cerebral cortex can provide valuable information about normal and abnormal neuroanatomy. High resolution MRI together with powerful image processing techniques has made it possible to perform these measurements automatically over the whole brain. Here we present a method for automatically generating voxel-based cortical thickness (VBCT) maps. This technique results in maps where each voxel in the grey matter is assigned a thickness value. Sub-voxel measurements of thickness are possible using sub-sampling and interpolation of the image information. The method is applied to repeated MRI scans of a single subject from two MRI scanners to demonstrate its robustness and reproducibility. A simulated data set is used to show that small focal differences in thickness between two groups of subjects can be detected. We propose that the analysis of VBCT maps can provide results that are complementary to other anatomical analyses such as voxel-based morphometry.

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Effects of shifting perspective of the self: An fMRI study.

Publication Date: 2008 May 1 PMID: 18325789
Authors: Corradi-Dell'acqua, C. - Ueno, K. - Ogawa, A. - Cheng, K. - Rumiati, R. I. - Iriki, A.
Journal: Neuroimage

When looking to our reflection, or moving a video-game character, we see our own movement preformed by an agent which is physically separated from our body. Yet, we consider the agent to be ourself. Using fMRI, we sought to explore the neural underpinnings of disembodiment, the cognitive mechanism under which the properties of the self are projected away from the boundaries of one's own body towards an external entity. Seventeen participants watched a video-game in which three players threw each other a ball. Subjects' key-press could either be synchronous or asynchronous with one of the players' action (TASK: Agency vs. Control). The game was shown from one of four viewpoints which could either be fixed or change every trial (VIEWS: Fixed vs. Changeable). Consistent with previous studies, the left insula was activated when the agent's movements were synchronous with those of the participants (main effect of TASK, p<0.05, SVC). The analysis of the interaction TASKVIEWS revealed activation (p<0.05, corrected) of the right parieto-temporal-occipital (PTO) junction when the agent whose movements were synchronous to the participants was processed in a spatial position each time different with respect to the preceding trials. Our findings implicate the right PTO junction in assigning one's own movements to an agent which is physically independent of oneself. They also suggest that the ability to disembody, and thereby objectify, bodily or mental states concerning the self is common to all experimental paradigms which led to an activation of the PTO junction.

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The cortical energy needed for conscious perception.

Publication Date: 2008 May 1 PMID: 18321731
Authors: Scholvinck, M. L. - Howarth, C. - Attwell, D.
Journal: Neuroimage

The brain's information processing power is limited by its energy supply but the allocation of cortical energy use between conscious and unconscious information processing is unknown. We calculate, from electrophysiological data in primates, that conscious perception reflects surprisingly small local alterations in mean cortical neuronal firing rate and energy consumption: perceiving visual stimulus movement, altered tactile vibration frequency, or tone stream separation, changes local cortical energy use by less than 6%. Our estimations of energy use suggest that a "design strategy", of encoding signals using separate neurons that increase and decrease their firing rate, serves to minimise changes of energy use in the cortical areas mediating perception and may result in stimulus perception failing to be detected by BOLD functional imaging.

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Myelin water imaging of multiple sclerosis at 7 T: Correlations with histopathology.

Publication Date: 2008 May 1 PMID: 18321730
Authors: Laule, C. - Kozlowski, P. - Leung, E. - Li, D. K. - Mackay, A. L. - Moore, G. R.
Journal: Neuroimage

Myelin water imaging (MWI) promises to be invaluable in understanding neurological diseases like MS. However, a limitation of MWI is signal to noise ratio. Recently, a number of investigators have performed MWI at field strengths higher than 1.5 T. Our goal was to determine if myelin water imaging at increased SNR, arising from the use of a small bore 7 T MR system with optimized coil geometry, enables the production of superior myelin water maps with increased spatial detail and enables better correlations with histology. Ten formalin-fixed MS brain samples underwent a 32-echo T(2) relaxation experiment which measured myelin water fraction (MWF) on a 7-T animal MRI scanner. MWF correlated strongly qualitatively and quantitatively with luxol fast blue staining for myelin [mean (range): R(2)=0.78 (0.56-0.95), p<0.0001]. The quality and detail of 7 T myelin water maps were far superior to that previously seen at 1.5 T, allowing for visualization of fine structures such as the normal prominent myelination of the deeper cortical layers, the alveus of the hippocampus and rings of preserved myelin in a concentric Balo's lesion. 7 T imaging will allow detailed assessment of myelin pathology to a degree not possible with lower field strengths.

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