Neuroimage

In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be perceived as gender-specific. Given that functional neuro-imaging correlates of AVHs involve multiple brain regions principally including auditory cortex, it is likely that those brain regions responsible for attribution of gender to speech are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and a paradigm utilising Fgender-apparent_ (unaltered) and Fgender-ambiguous_ (pitch-scaled) male and female voice stimuli to test the hypothesis that male and female voices activate distinct brain areas during gender attribution. The perception of female voices, when compared with male voices, affected greater activation of the right anterior superior temporal gyrus, near the superior temporal sulcus. Similarly, male voice perception activated the mesio-parietal precuneus area. These different gender associations could not be explained by either simple pitch perception or behavioural response because the activations that we observed were conjointly activated by both Fgender-apparent_ and Fgender-ambiguous_ voices. The results of this study demonstrate that, in the male brain, the perception of male and female voices activates distinct brain regions. D

Previous studies have shown activation of right orbitofrontal cortex during judgments of odor familiarity. In the present study, we sought to extend our knowledge about the neural circuits involved in such a task by exploring the involvement of the right prefrontal areas and limbic/ primary olfactory structures. Fourteen right-handed male subjects were tested using fMRI with a single functional run of two olfactory conditions (odor detection and familiarity judgments). Each condition included three epochs. During the familiarity condition, subjects rated whether odors were familiar or unfamiliar. During the detection condition, participants decided if odors were present. When contrasting the familiarity with the detection conditions, activated areas were found mainly in the right piriform cortex (PC) and hippocampus, the left inferior frontal gyrus and amygdala, and bilaterally in the mid-fusiform gyrus. Further analyses demonstrated that the right PC was more strongly activated than the left PC. This result supports the notion that the right PC is preferentially involved in judgments of odor familiarity. D

Cognition is thought to result from interactions within large-scale networks of brain regions. Here we propose a method to identify these large-scale networks using functional magnetic resonance imaging (fMRI). Regions belonging to such networks are defined as sets of strongly interacting regions, each of which showing an homogeneous temporal activity. Our method of large-scale network identification (LSNI) proceeds by first detecting functionally homogeneous regions. The networks of functional interconnections are then found by comparing the correlations among these regions against a model of the correlations in the noise.

Recent research has demonstrated that cortical motor areas are engaged when observing motor actions of others. However, little is known about the possible contribution of the motor system for evaluating the correctness of others' actions. To address this question we designed an MEG experiment in which subjects were executing and observing motor actions with and without errors. In the execution task subjects were asked to make speeded button presses according to instruction cues. During the observation task, they viewed pictures of an actor's hand making button presses which were correct or incorrect according to the cues. Time-frequency representations of the MEG data demonstrated a depression in oscillatory activity in the beta band activity (15-35 Hz) during execution followed by a beta rebound that was stronger for incorrect compared to correct executions. During the observation task, a similar time-course of the beta activity was identified and importantly the modulations were stronger for the observation of incorrect than correct actions. Sources accounting for the difference in beta activity between correct and incorrect actions were localized using a beamforming technique. Both for the execution and observation conditions sources were identified to the dorsal motor areas comprising both primary and pre-motor cortex. Our findings demonstrate that not only is cortical motor activity modulated by action observation, but the modulation increases when the observed action is erroneous. This suggests that the motor system is engaged in evaluating the correctness of the actions of others.

The functional anatomy of Chinese character processing was investigated using fMRI. Right-handed Mandarin-English bilingual participants made either semantic or perceptual size judgements with characters and pictures. Areas jointly activated by character and picture semantic tasks compared to size judgement tasks included the left prefrontal region (BA 9, 44, 45), left posterior temporal, left fusiform, and left parietal regions. Character processing produced greater activation than picture processing in the left mid and posterior temporal as well as left prefrontal regions. The lateral occipital regions were more active during picture semantic processing than character semantic processing. A similar pattern of activation and contrasts was observed when English words and pictures were compared in another set of bilingual participants. However, there was less contrast between word and picture semantic processing than between character and picture processing in the left prefrontal region. When character and word semantic processing were compared directly in a third group, the loci of activation peaks was similar in both languages but Chinese character semantic processing was associated with a larger MR signal change. The semantic processing of Chinese characters, English words, and pictures activates a common semantic system within which there are modality-specific differences. The semantic processing of Chinese characters more closely resembles English words than pictures.

Recently, structural MRI studies in children have been used to examine relations between brain volume and behavioral measures. However, most of these studies have been done in children older than 2 years of age. Obtaining volumetric measures in infants is considerably more difficult, as structures are less well defined and largely unmyelinated, making segmentation challenging. Moreover, it is still unclear whether individual anatomic variation across development, in healthy, normally developing infants, is reflected in the configuration and function of the mature brain and, as importantly, whether variation in infant brain structure might be related to later cognitive and linguistic abilities. In this longitudinal study, using T1 structural MRI, we identified links between amygdala volume in normally developing, naturally sleeping, 6-month infants and their subsequent language abilities at 2, 3 and 4 years. The images were processed and manually segmented using Cardviews to extract volumetric measures. Intra-rater reliability for repeated segmentation was 87.73% of common voxel agreement. Standardized language assessments were administered at 6 and 12 months and at 2, 3 and 4 years. Significant and consistent correlations were found between amygdala size and language abilities. Children with larger right amygdalae at 6 months had lower scores on expressive and receptive language measures at 2, 3, and 4 years. Associations between amygdala size and language outcomes have been reported in children with autism. The findings presented here extend this association to normally developing children, supporting the idea that the amygdalae might play an important but as yet unspecified role in mediating language acquisition.

The Human Connectome Project (HCP) has developed protocols, standard operating and quality control procedures, and a suite of informatics tools to enable high throughput data collection, data sharing, automated data processing and analysis, and data mining and visualization. Quality control procedures include methods to maintain data collection consistency over time, to measure head motion, and to establish quantitative modality-specific overall quality assessments. Database services developed as customizations of the XNAT imaging informatics platform support both internal daily operations and open access data sharing. The Connectome Workbench visualization environment enables user interaction with HCP data and is increasingly integrated with the HCP's database services. Here we describe the current state of these procedures and tools and their application in the ongoing HCP study.

The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI data provides measures of damage, which are key criteria for the diagnosis, prognosis, and longitudinal monitoring in MS. Automating this operation eliminates inter-rater variability and increases the efficiency of large-throughput analysis pipelines. Robust and reliable segmentation across multi-site spinal cord data is challenging because of the large variability related to acquisition parameters and image artifacts. The goal of this study was to develop a fully-automatic framework, robust to variability in both image parameters and clinical condition, for segmentation of the spinal cord and intramedullary MS lesions from conventional MRI data. Scans of 1,042 subjects (459 healthy controls, 471 MS patients, and 112 with other spinal pathologies) were included in this multi-site study (n=30). Data spanned three contrasts (T1-, T2...

A three-fold enhanced risk of schizophrenia is conferred by learning disability. Here we use voxel-based morphometry (VBM) to investigate grey matter correlates of early psychotic and related symptoms in 137 adolescents at enhanced risk of this disorder because of intellectual disability. Anxiety, hallucinations, incoherence of speech and delusions were assessed at clinical interview, and VBM was used to examine linear associations between symptom severity and grey matter density (GMD). We found significant correlations between anxiety and GMD in the right dorsomedial thalamic nucleus, left parahippocampal gyrus and left hippocampus. Incoherence of speech was associated with GMD in the left cerebellar hemisphere. Gender-separate analysis demonstrated correlations between anxiety and GMD in the right dorsomedial thalamic nucleus of males and the right pulvinar nucleus of females, hallucinations and GMD in the right STG of males, delusions and GMD in the left middle temporal gyrus (MTG) of females, and incoherence of speech and GMD in the right MTG of males and both cerebellar hemispheres and right inferior temporal gyrus of females. Findings are consistent with symptomstructure associates previously reported in populations with schizophrenia or at enhanced genetic risk, and suggest an anatomical basis for the psychopathology found in this young nonclinical population.

The question whether brain activity is temporally or spatially correlated arises when dealing with Principal Component Analysis @CA) and Independent Component Analysis (ICA) for analyzing functional magnetic resonance imaging (fMRI) data. These methods draw increasing attention, because they are data driven and hence do not need a priori information about a stimulus. The two methods are able to extract multiple components of brain activity based on the assumption that there exists a set of underlying brain processes which are., respectively, mutually uncorrelated or statistically independent. Temporal or spatial aspects of the experimental data are emphasized by considering the data either as a set of time sequences reflecting the time-variant activities of single voxels or as a set of images reflecting the activity distribution at a given time.

Neuroimaging experiments have revealed that the visual cortex is involved in the processing of affective stimuli: seeing emotional pictures leads to greater activation than seeing neutral ones. It is unclear, however, whether such differential activation is due to stimulus valence or whether the results are confounded by arousal level. In order to investigate the contributions of valence and arousal to visual activation, we created a new category of "interesting" stimuli designed to have high arousal, but neutral valence, and employed standard neutral, unpleasant, and pleasant picture categories. Arousal ratings for pleasant and neutral pictures were equivalent, as were valence ratings for interesting and neutral pictures. Differential activation for conditions matched for arousal (pleasant vs neutral) as well as matched for valence (interesting vs neutral) indicated that both stimulus valence and arousal contributed to visual activation.

The anterior cingulate cortex (ACC) is thought to be the neuroanatomical interface between emotion and cognition. Because effective emotion-cognition interactions are essential to optimal decision making, clarifying how the functionality of the ACC changes in older age using functional imaging holds great promise for ultimately understanding what contributes to the psychological changes occurring in late life. However, the interpretation of functional imaging studies is complicated by the fact that aging is associated with changes in grey matter volume and in the cerebral vasculature. In the present study, we obtained high-resolution structural magnetic resonance (MR) imaging data and quantitative blood flow images to examine the association between aging, blood flow, and grey matter volume in the ACC. Twenty-six healthy individuals between 25 and 79 years of age underwent quantitative [ 15 O]water positron emission tomography (PET) imaging. The ACC was traced onto tissue-classified images derived from T1-and T2-weighted MRIs using previously defined methods. The ACC was divided into dorsal, rostral, and subgenual regions. Age was negatively correlated with blood flow in dorsal and rostral ACC regions. Effects were weaker but in a similar direction for the subgenual ACC. While older age and lower blood flow were both associated with smaller rostral ACC grey matter volumes, mediation analysis revealed that grey matter volume only partially mediated the effect of age on blood flow in the rostral ACC. Neural alterations not detectable on MR images may lead to reduced blood flow due to fewer and/or less metabolically active neurons. Alternatively, lower blood flow may be a cause, rather than a consequence, of smaller grey matter volume in the ACC. M., 2002. Changes in regional cerebral blood flow abnormalities in late-life depression following response to electroconvulsive therapy. Psychiatry Clin. Neurosci. 56, 31-40. Baron, R.M., Kenny, D.A., 1986. The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J. Pers. Soc. Psychol. 51, 1173-1182. Bennett, S.A., Tenniswood, M., Chen, J.H., Davidson, C.M., Keyes, M.T., Fortin, T., Pappas, B.A., 1998. Chronic cerebral hypoperfusion elicits neuronal apoptosis and behavioral impairment. NeuroReport 9, 161-166. ., 2001. Hippocampal and anterior cingulate activation deficits in patients with geriatric depression. Am. J. Psychiatry 158, 1321-1323. Denburg, N.L., Recknor, E.C., Bechara, A., Tranel, D., 2006. Psychophysiological anticipation of positive outcomes promotes advantageous decision-making in normal older persons. Int. J. Psychophysiol. 61, 19-25. Devinsky, O., Morrell, M.J., Vogt, B.A., 1995. Contributions of anterior cingulate cortex to behaviour. Brain 118, 279-306.

Cortical flattening algorithms are becoming more widely used to assist in visualizing the convoluted cortical gray matter sheet of the brain. Metric-based approaches are the most common but suffer from high distortions. Conformal, or angle-based algorithms, are supported by a comprehensive mathematical theory. The conformal approach that uses circle packings is versatile in the manipulation and display of results. In addition, it offers some new and interesting metrics that may be useful in neuroscientific analysis and are not available through numerical partial differential equation conformal methods. In this paper, we begin with a brief description of cortical bflatQ mapping, from data acquisition to map displays, including a brief review of past flat mapping approaches. We then describe the mathematics of conformal geometry and key elements of conformal mapping. We introduce the mechanics of circle packing and discuss its connections with conformal geometry. Using a triangulated surface representing a cortical hemisphere, we illustrate several manipulations available using circle packing methods and describe the associated bensemble conformal featuresQ (ECFs). We conclude by discussing current and potential uses of conformal methods in neuroscience and computational anatomy. D 2004 Elsevier Inc. All rights reserved.

Based on the hypothesis that brain plaques and tangles can affect cortical function in Alzheimer's disease (AD), we investigated functional responses in an AD rat model (called the Samaritan Alzheimer's rat achieved by ventricular infusion of amyloid peptide) and age-matched healthy control. High-field functional magnetic resonance imaging (fMRI) and extracellular neural activity measurements were applied to characterize sensory-evoked responses. Electrical stimulation of the forepaw led to BOLD and neural responses in the contralateral somatosensory cortex and thalamus. In AD brain we noted much smaller BOLD activation patterns in the somatosensory cortex (i.e., about 50% less activated voxels compared to normal brain). While magnitudes of BOLD and neural responses in the cerebral cortex were markedly attenuated in AD rats compared to normal rats (by about 50%), the dynamic coupling between the BOLD and neural responses in the cerebral cortex, as assessed by transfer function analysis, remained unaltered between the groups. However thalamic BOLD and neural responses were unaltered in AD brain compared to controls. Thus cortical responses in the AD model were indeed diminished compared to controls, but the thalamic responses in the AD and control rats were quite similar. Therefore these results suggest that Alzheimer's disease may affect cortical function more than subcortical function, which may have implications for interpreting altered human brain functional responses in fMRI studies of Alzheimer's disease.

Prior evidence has suggested a link between caudate dopaminergic functioning and cognition in Parkinson's disease (PD). In this dual tracer study we analyzed the relationship between nigrostriatal dopaminergic dysfunction and the expression of the previously validated PD cognition-related metabolic pattern (PDCP). In this study, 17 non-demented PD patients underwent positron emission tomography (PET) imaging with [ 18 F]-fluorodeoxyglucose to measure PDCP expression, and [ 18 F]-fluoropropyl-β-CIT (FPCIT) to measure dopamine transporter (DAT) binding. Automated voxel-by-voxel searches of the FPCIT PET volumes were performed to identify regions in which DAT binding significantly correlated with PDCP expression values. The findings were validated using prespecified anatomical regions-of-interest (ROIs). Voxel-wise interrogation of the FPCIT PET scans revealed a single significant cluster in which DAT binding correlated with PDCP expression (p b 0.05, corrected). This cluster was localized to the left caudate nucleus; an analogous correlation (r = − 0.63, p b 0.01) was also present in the "mirror" region of the right hemisphere. These findings were confirmed by the presence of a significant correlation (r = −0.67, p b 0.005) between PDCP expression and DAT binding in caudate ROIs, which survived adjustment for age, disease duration, and clinical severity ratings. Correlation between caudate DAT binding and subject expression of the PD motor-related metabolic pattern was not significant (p > 0.21). In summary, this study demonstrates a significant relationship between loss of dopaminergic input to the caudate nucleus and the expression of a cognition-related disease network in unmedicated PD patients. These baseline measures likely function in concert to determine the cognitive effects of dopaminergic therapy in PD.

In this paper, we present a novel automated method for White Matter (WM) lesion segmentation of Multiple Sclerosis (MS) patient images. Our approach is based on a cascade of two 3D patch-wise convolutional neural networks (CNN). The first network is trained to be more sensitive revealing possible candidate lesion voxels while the second network is trained to reduce the number of misclassified voxels coming from the first network. This cascaded CNN architecture tends to learn well from a small (n≤35) set of labeled data of the same MRI contrast, which can be very interesting in practice, given the difficulty to obtain manual label annotations and the large amount of available unlabeled Magnetic Resonance Imaging (MRI) data. We evaluate the accuracy of the proposed method on the public MS lesion segmentation challenge MICCAI2008 dataset, comparing it with respect to other state-of-the-art MS lesion segmentation tools. Furthermore, the proposed method is also evaluated on two private M...

While neuroimaging studies implicate medial rostral prefrontal cortex (mrPFC) in self-referential processing, simulation accounts of social cognition suggest that this region also supports thinking about other people. This study tested the prediction that mrPFC might be involved in appraising the personality traits of another person to the degree that this person is perceived as similar to oneself. We also examined whether recruiting common processes for thinking about oneself and others might impact on subsequent memory for those judgments. Functional MRI was used while two factors were crossed: (i) the requirement to engage in personality trait or episodic source memory judgments and (ii) the reference for these judgments (i.e., oneself or a friend). The results link haemodynamic changes in mrPFC to both personality judgments about oneself and subsequent episodic memory retrieval of these judgments. The degree to which BOLD signal in this region was also associated with thinking about others correlated with perceived similarity in both tasks, thus corroborating simulation accounts. Moreover, participants who perceived themselves as having similar traits to their friends tended to be poorer at remembering whether they had made trait judgments in reference to themselves or their friend. This behavioral effect was reflected in the BOLD signal in mrPFC: there was a positive correlation between signal change for self versus friend judgments and subsequent memory for the reference of such judgments. The results suggest that investigations of mrPFC activity in the context of self/other judgments should take into account this psychological similarity effect.

Cerebral Cortex-to study correlated changes within and across different cortical networks. The principal topic of investigation is whether the thickness of one area of the cortex changes in a statistically correlated fashion with changes in thickness of other cortical regions. We further extend these methods by introducing techniques to test whether different population groupings exhibit significantly varying MACACC patterns. The methods are described in detail and applied to a normal childhood development population (n = 292), and show that association cortices have the highest correlation strengths. Taking Brodmann Area (BA) 44 as a seed region revealed MACACC patterns strikingly similar to tractography maps obtained from diffusion tensor imaging. Furthermore, the MACACC map of BA 44 changed with age, older subjects featuring tighter correlations with BA 44 in the anterior portions of the superior temporal gyri. Lastly, IQ-dependent MAC-ACC differences were investigated, revealing steeper correlations between BA 44 and multiple frontal and parietal regions for the higher IQ group, most significantly (t = 4.0) in the anterior cingulate. D

We used functional magnetic resonance imaging of healthy subjects to investigate the neural basis for spontaneous "willed" action. We hypothesised that such action involves prefrontal cortex (PFC) and supplementary motor area (SMA), in addition to primary motor cortex. Furthermore, we predicted that PFC and SMA would demonstrate similar temporal response dynamics, distinct from primary motor cortex. Specifically, we predicted earlier activation in PFC and SMA, manifest as shorter response latencies compared with primary motor cortex. Six right-handed males participated in an event-related design and were required to generate spontaneous motor acts inside the scanner. By deciding "which" of two buttons to press, and "when" to press them, subjects generated sequences of action that were of high information content ("novelty" or "randomness"). Utilising a short repetition time (1 s), we acquired functional images that covered most of the frontal and parietal cortices. The onset of action was associated with significant activation in bilateral PFC, left primary motor cortex, and, close to the midline, SMA. Following action, mean time to half-maximum blood oxygenation level-dependent response was significantly earlier in left PFC and SMA than primary motor cortex. Our findings suggest that neural correlates of spontaneous willed action are distributed in executive and motor centres, and that temporal response dynamics differentiate "higher" regions from subordinate motor areas.

System development for Image-Guided Therapy (IGT), or Image-Guided Interventions (IGI), continues to be an area of active interest across academic and industry groups. This is an emerging field that is growing rapidly: major academic institutions and medical device manufacturers have produced IGT technologies that are in routine clinical use, dozens of high-impact publications are published in well regarded journals each year, and several small companies have successfully commercialized sophisticated IGT systems. In meetings between IGT investigators over the last two years, a consensus has emerged that several key areas must be addressed collaboratively by the community to reach the next level of impact and efficiency in IGT research and development to improve patient care. These meetings culminated in a two-day workshop that brought together several academic and industrial

Background: The amygdala plays a central role in the human response to affective or emotionally charged stimuli, particularly fear-producing stimuli. We examined the specificity of the amygdala response to facial expressions in adults and children.Methods: Six adults and 12 children were scanned in a 1.5-T scanner during passive viewing of fearful and neutral faces using an EPI BOLD sequence. All scans were registered to a reference brain, and analyses of variance were conducted on the pooled data to examine interactions with age and gender.Results: Overall, we observed predominantly left amygdala and substantia innominata activity during the presentation of nonmasked fearful faces relative to fixation, and a decrease in activation in these regions with repeated exposure to the faces. Adults showed increased left amygdala activity for fearful faces relative to neutral faces. This pattern was not observed in the children who showed greater amygdala activity with neutral faces than with fearful faces. For the children, there was an interaction of gender and condition whereby boys but not girls showed less activity with repeated exposure to the fearful faces.Conclusions: This is the first study to examine developmental differences in the amygdala response to facial expressions using functional magnetic resonance imaging.

a b s t r a c t Available online xxxx Connectivity analysis of fMRI data requires correct specification of regions-of-interest (ROIs). Selection of ROIs based on outcomes of a GLM analysis may be hindered by conservativeness of the multiple comparison correction, while selection based on brain anatomy may be biased due to inconsistent structure-to-function mapping. To alleviate these problems we propose a method to define functional ROIs without the need for a stringent multiple comparison correction. We extend a flexible framework for fMRI analysis (Activated Region Fitting, ) to connectivity analysis of fMRI data. This method describes an entire fMRI data volume by regions of activation defined by a limited number of parameters. Therefore a less stringent multiple comparison procedure is required. The regions of activation from this analysis can be directly used to estimate functional connectivity. Simulations show that Activated Region Fitting can recover the connectivity of brain regions. An application to real data of a Go/No-Go experiment highlights the advantages of the method.

Humor is a uniquely human quality whose neural substrates remain enigmatic. The present report combined dynamic, real-life content and event-related functional magnetic resonance imaging (fMRI) to dissociate humor detection (''getting the joke'') from humor appreciation (the affective experience of mirth). During scanning, subjects viewed full-length episodes of the television sitcoms Seinfeld or The Simpsons. Brain activity time-locked to humor detection moments revealed increases in left inferior frontal and posterior temporal cortices, whereas brain activity time-locked to moments of humor appreciation revealed increases in bilateral regions of insular cortex and the amygdala. These findings provide evidence that humor depends critically upon extant neural systems important for resolving incongruities (humor detection) and for the expression of affect (humor appreciation).

Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala involvement in memory for emotionally arousing material. Here, we examine the possibility that sex-related differences in amygdala involvement in memory for emotional material develop from differential patterns of amygdala functional connectivity evident in the resting brain. Seed voxel partial least square analyses of regional cerebral blood flow data revealed significant sex-related differences in amygdala functional connectivity during resting conditions. The right amygdala was associated with greater functional connectivity in men than in women. In contrast, the left amygdala was associated with greater functional connectivity in women than in men. Furthermore, the regions displaying stronger functional connectivity with the right amygdala in males (sensorimotor cortex, striatum, pulvinar) differed from those displaying stronger functional connectivity with the left amygdala in females (subgenual cortex, hypothalamus). These differences in functional connectivity at rest may link to sex-related differences in medical and psychiatric disorders. D

Brain activity during observation and imagery of gait was investigated. Sixteen subjects were scanned with a 3-Tesla MRI scanner while viewing six types of video clips: observation of gait movement (GO) from the third-person perspective, observation of stepping movement, observation of standing posture, "virtual walking" (VW) that was observation of visual scenes mimicking the visual afferent during walking, and the scrambled version of the GO and VW stimuli. In the VW condition, moving scenes provided a virtual visual environment in which subjects easily imagined as if they were actually walking from the first-person perspective. A behavioral experiment revealed a correlation of cadence during actual walking with that during imaginary walking under the influence of the VW stimuli, indicating that a gait planning mechanism was shared by actual walking and gait imagery. The VW condition activated the dorsal premotor cortex (PMd), supplementary motor area/cingulate motor area (SMA/CMA), parahippocampal gyrus, and subcortical nuclei. The GO stimuli yielded activation of the SMA, PMd, inferior frontal gyrus, and inferior parietal lobule. Moreover, the conjunction null test of GO and VW revealed common activity in the SMA/CMA and PMd, which were reportedly active during actual gait movement, in addition to visual areas. Detailed analyses of activity during stepping or standing observation supported the specificity of the SMA and PMd to GO. These findings suggest that motor planning centers of gait, including the SMA and PMd, are activated during both imagination (first-person perspective) and observation (third-person perspective) of gait behaviors.

This paper is concerned with the problem of evaluating goodness-of-fit of a path analytic model to an interregional correlation matrix derived from functional magnetic resonance imaging (fMRI) data. We argue that model evaluation based on testing the null hypothesis that the correlation matrix predicted by the model equals the population correlation matrix is problematic because P values are conditional on asymptotic distributional results (which may not be valid for fMRI data acquired in less than 10 min), as well as arbitrary specification of residual variances and effective degrees of freedom in each regional fMRI time series. We introduce an alternative approach based on an algorithm for automatic identification of the best fitting model that can be found to account for the data. The algorithm starts from the null model, in which all path coefficients are zero, and iteratively unconstrains the coefficient which has the largest Lagrangian multiplier at each step until a model is identified which has maximum goodness by a parsimonious fit index. Repeating this process after bootstrapping the data generates a confidence interval for goodness-of-fit of the best model. If the goodness of the theoretically preferred model is within this confidence interval we can empirically say that the theoretical model could be the best model. This relativistic and data-based strategy for model evaluation is illustrated by analysis of functional MR images acquired from 20 normal volunteers during periodic performance (for 5 min) of a task demanding semantic decision and subvocal rehearsal. A model including unidirectional connections from frontal to parietal cortex, designed to represent sequential engagement of rehearsal and monitoring components of the articulatory loop, is found to be irrefutable by hypothesis-testing and within confidence limits for the best model that could be fitted to the data.

Volumetric MRI studies based on manual labeling of selected anatomical structures have provided in vivo evidence that brain abnormalities associated with temporal lobe epilepsy (TLE) extend beyond the hippocampus. Voxel-based morphometry (VBM) is a fully automated image analysis technique allowing identification of regional differences in gray matter (GM) and white matter (WM) between groups of subjects without a prior region of interest. The purpose of this study was to determine whole-brain GM and WM changes in TLE and to investigate the relationship between these abnormalities and clinical parameters. We studied 85 patients with pharmacologically intractable TLE and unilateral hippocampal atrophy and 47 age-and sex-matched healthy control subjects. The seizure focus was right sided in 40 patients and left sided in 45. Student's t test statistical maps of differences between patients' and controls' GM and WM concentrations were obtained using a general linear model. A further regression against duration of epilepsy, age of onset, presence of febrile convulsions, and secondary generalized seizures was performed with the TLE population. Voxel-based morphometry revealed that GM pathology in TLE extends beyond the hippocampus involving other limbic areas such as the cingulum and the thalamus, as well as extralimbic areas, particularly the frontal lobe. White matter reduction was found only ipsilateral to the seizure focus, including the temporopolar, entorhinal, and perirhinal areas. This pattern of structural changes is suggestive of disconnection involving preferentially frontolimbic pathways in patients with pharmacologically intractable TLE. D 2004 Elsevier Inc. All rights reserved.

When listening to speech under adverse conditions, expectancies resulting from semantic context can have a strong impact on comprehension. Here we ask how minimal variations in semantic context (cloze probability) affect the unfolding comprehension of acoustically degraded speech. Three main results are observed in the brain electric response. First, auditory evoked responses to a degraded sentence's onset (N100) correlate with participants' comprehension scores, but are generally more vigorous for more degraded sentences. Second, a pronounced N400 in response to low-cloze sentence-final words, reflecting the integration effort of words into context, increases linearly with improving speech intelligibility. Conversely, transient enhancement in Gamma band power (γ,~40-70 Hz) during high-cloze sentence-final words (~600 ms) reflects top-down-facilitated integration. This γ-band effect also varies parametrically with signal quality. Third, a negative correlation of N100 amplitude at sentence onset and the later γ-band response is found in moderately degraded speech. This reflects two partly distinct neural strategies when dealing with moderately degraded speech; a more "bottom-up," resource-allocating, and effortful versus a more "top-down," associative and facilitatory strategy. Results also emphasize the non-redundant contributions of phase-locked (evoked) and non-phase-locked (induced) oscillatory brain dynamics in auditory EEG.

Is it living or not? The ability to differentiate between animate and inanimate entities is of considerable value in everyday life, since it allows for the dissociation of individuals that may willfully cause an action from objects that cannot. The present fMRI study aimed to shed light on the neural correlates of animacy at a relational-interpretive level, i.e. on the role of animacy in the establishment of relations between entities that are more or less likely to cause an event and differ in their potential to act volitionally. To this end, we investigated the processing of visually presented transitive German sentences (nominative-accusative structures) in which the factors animacy and argument order were manipulated. The relations between the arguments differed in that the animate subject either acted on an inanimate object (a very natural construction in terms of transitivity) or on an animate object (resulting in a sentence deviating from an unmarked transitive structure). Participants performed an acceptability judgment task. Violations of unmarked transitivity yielded a significant activation increase within the posterior left superior temporal sulcus (pSTS), thus suggesting a specific role of this cortical region in the relational use of animacy information. This result indicates that the influence of animacy as a relational feature differs from the impact of this parameter on the word level and is in line with other neuroimaging studies showing an engagement of the pSTS when a matching between syntax and semantics is required. A comparison between object-and subject-initial conditions further revealed a robust effect of argument order in the pars opercularis of the left inferior frontal gyrus (a subregion of Broca's area), thereby replicating previous findings demonstrating a sensitivity of this region to finegrained language-specific linearization rules.

The functional role of human premotor and primary motor cortex during mental rotation has been studied using functional MRI at 3 T. Fourteen young, male subjects performed a mental rotation task in which they had to decide whether two visually presented cubes could be identical. Exploratory Fuzzy Cluster Analysis was applied to identify brain regions with stimulus-related time courses. This revealed one dominant cluster which included the parietal cortex, premotor cortex, and dorsolateral prefrontal cortex that showed signal enhancement during the whole stimulus presentation period, reflecting cognitive processing. A second cluster, encompassing the contralateral primary motor cortex, showed activation exclusively after the button press response. This clear separation was possible in 3 subjects only, however. Based on these exploratory results, the hypothesis that primary motor cortex activity was related to button pressing only was tested using a parametric approach via a random-effects group analysis over all 14 subjects in SPM99. The results confirmed that the stimulus response via button pressing causes activation in the primary motor cortex and supplementary motor area while parietal cortex and mesial regions rostral to the supplementary motor area are recruited for the actual mental rotation process.

Independent component analysis (ICA) has been widely used in data analysis and decomposition for neuroimaging. It, typically, aims to solve the blind source separation problem in which a set of unknown sources is mixed in some way to form the data. Wavelet analysis has also become routinely used in neuroimaging, especially in PET image analysis. Here, we investigate the feasibility of combining ICA with wavelet models in order to integrate the advantages of both underlying techniques. Wavelets are well known to have sparse signal representation, and thus it should be more feasible to decompose the underlying unknown sources . ICA is not a linear technique, and hence analysis in the image domain and wavelet domain will not lead to equivalent solutions. We have investigated using ICA dynamic PET data both in the image domain and in the wavelet domain, where the data had been transformed using Battle-Lemarie wavelets as in . That data was analyzed with ICA, resulting in two kinds of components -a spatial component and a temporal component . Each component pair gives the spatial distribution of that temporal component. For each pair, the mean variance of the component can be calculated and used to rank the components in a similar way to eigenvalues in principle component analysis. Hybrid wavelet-ICA should require far fewer components for signal representation than its image domain equivalent as the signal and noise are well separated. Below are the results of applying the method to a [11C]-Raclopride scan. As can be seen, better denoising . Comparison of ICA and wavelet-ICA for a [ 11 C]-Raclopride data set. Component pairs -spatial and temporal -are generated. Using the mean variance of each component pair, the five components with largest mean variance are preserved and used to estimate BP.

A prevailing neurobiological theory of semantic memory proposes that part of our knowledge about concrete, highly imageable concepts is stored in the form of sensory -motor representations. While this theory predicts differential activation of the semantic system by concrete and abstract words, previous functional imaging studies employing this contrast have provided relatively little supporting evidence. We acquired event-related functional magnetic resonance imaging (fMRI) data while participants performed a semantic similarity judgment task on a large number of concrete and abstract noun triads. Task difficulty was manipulated by varying the degree to which the words in the triad were similar in meaning. Concrete nouns, relative to abstract nouns, produced greater activation in a bilateral network of multimodal and heteromodal association areas, including ventral and medial temporal, posterior -inferior parietal, dorsal prefrontal, and posterior cingulate cortex. In contrast, abstract nouns produced greater activation almost exclusively in the left hemisphere in superior temporal and inferior frontal cortex. Increasing task difficulty modulated activation mainly in attention, working memory, and response monitoring systems, with almost no effect on areas that were modulated by imageability. These data provide critical support for the hypothesis that concrete, imageable concepts activate perceptually based representations not available to abstract concepts. In contrast, processing abstract concepts makes greater demands on left perisylvian phonological and lexical retrieval systems. The findings are compatible with dual coding theory and less consistent with single-code models of conceptual representation. The lack of overlap between imageability and task difficulty effects suggests that once the neural representation of a concept is activated, further maintenance and manipulation of that information in working memory does not further increase neural activation in the conceptual store. D

Nonlinear effects in fMRI BOLD data may substantially influence estimates of task-related activations, particularly in rapid eventrelated designs. If the BOLD response to each stimulus is assumed to be independent of the stimulation history, nonlinear interactions create a prediction error that may reduce sensitivity. When stimulus density differs among conditions, nonlinear effects can cause artifactual differences in activation. This situation can occur in rapid event-related designs or when comparing blocks of unequal lengths. We present data showing substantial nonlinear history effects for stimuli 1 s apart and use estimates of nonlinearities in response magnitude, onset time, and time to peak to form a low-dimensional parameterization of these nonlinear effects. Our estimates of nonlinearity appear relatively consistent throughout the brain, and these estimates can be used to form adjusted linear predictors for future rapid event-related fMRI studies. Adjusting the linear model for these known nonlinear effects results in a substantially better model fit. The biggest advantages to using predictors adjusted for known nonlinear effects are (1) higher sensitivity at the individual subject level of analysis, (2) better control of confounds related to nonlinear effects, and (3) more accurate estimates of design efficiency in experimental fMRI design. D

The basis for different neural activations in response to male and female voices as well as the question, whether men and women perceive male and female voices differently, has not been thoroughly investigated. Therefore, the aim of the present study was to examine the behavioral and neural correlates of gender-related voice perception in healthy male and female volunteers. fMRI data were collected while 39 participants (19 female) were asked to indicate the gender of 240 voice stimuli. These stimuli included recordings of 3-syllable nouns as well as the same recordings pitch-shifted in 2, 4 and 6 semitone steps in the direction to the other gender. Data analysis revealed a) equal voice discrimination sensitivity in men and women but better performance in the categorization of opposite-sex stimuli at least in men, b) increased responses to increasing gender ambiguity in the mid cingulate cortex and bilateral inferior frontal gyri, and c) stronger activation in a fronto-temporal neur...

Neuroscientific data is typically analyzed based on the behavioral response of the participant. However, the errors made may or may not be in line with the neural processing. In particular in experiments with time pressure or studies where the threshold of perception is measured, the error distribution deviates from uniformity due to the structure in the underlying experimental set-up. When we base our analysis on the behavioral labels as usually done, then we ignore this problem of systematic and structured (non-uniform) label noise and are likely to arrive at wrong conclusions in our data analysis. This paper contributes a remedy to this important scenario: we present a novel approach for a) measuring label noise and b) removing structured label noise. We demonstrate its usefulness for EEG data analysis using a standard d2 test for visual attention (N = 20 participants).