Adolescence is often described as a period of heightened reactivity to emotions paired with reduced regulatory capacities, a combination suggested to contribute to risk-taking and susceptibility to peer influence during puberty. However, no longitudinal research has definitively linked these behavioral changes to underlying neural development. Here, 38 neurotypical participants underwent two fMRI sessions across the transition from late childhood (10 years) to early adolescence (13 years). Responses to affective facial displays exhibited a combination of general and emotion-specific changes in ventral striatum (VS), ventromedial PFC, amygdala, and temporal pole. Furthermore, VS activity increases correlated with decreases in susceptibility to peer influence and risky behavior. VS and amygdala responses were also significantly more negatively coupled in early adolescence than in late childhood while processing sad and happy versus neutral faces. Together, these results suggest that VS responses to viewing emotions may play a regulatory role that is critical to adolescent interpersonal functioning.
The mirror neuron system (MNS) has been proposed to play an important role in social cognition by providing a neural mechanism by which others’ actions, intentions, and emotions can be understood. Here functional magnetic resonance imaging was used to directly examine the relationship between MNS activity and two distinct indicators of social functioning in typically-developing children (aged 10.1 years±7 months): empathy and interpersonal competence. Reliable activity in pars opercularis, the frontal component of the MNS, was elicited by observation and imitation of emotional expressions. Importantly, activity in this region (as well as in the anterior insula and amygdala) was significantly and positively correlated with established behavioral measures indexing children’s empathic behavior (during both imitation and observation) and interpersonal skills (during imitation only). These findings suggest that simulation mechanisms and the MNS may indeed be relevant to social functioning in everyday life during typical human development.
In the automatic imitation task (AIT) participants make a cued response during simultaneous exposure to a congruent or incongruent action made by another agent. Participants are slower to make the cued response on incongruent trials, which is thought to reflect conflict between the motor representation activated by the cue and the motor representation activated by the observed action. On incongruent trials, good performance requires the capacity to suppress the imitative action, in favor of producing the cued response. Here, we introduce a new experimental paradigm that complements the AIT, and is therefore a useful task for studying the control of self and other activated representations. In what we term the “Controlled Imitation Task (CIT)”, participants are cued to make an action, but on 50% of trials, within 100 ms of this cue, an on-screen hand makes a congruent or incongruent action. If the onscreen hand moves, the participant must suppress the cued response, and instead imitate the observed action as quickly and accurately as possible. In direct contrast to the AIT, the CIT requires suppression of a self-activated motor representation, and prioritization of an imitative response. In experiment 1, we report a robust pattern of interference effects in the CIT, such that participants are slower to make the imitative response on incongruent compared to congruent trials. In experiment 2, we replicate this effect while including a non-imitative spatial-cue control condition to show that the effect is particularly robust for imitative response tendencies per se. Owing to the essentially opposite control requirements of the CIT versus the AIT (i.e., suppression of self-activated motor representations instead of suppression of other-activated motor representations), we propose that this new task is a potentially informative complementary paradigm to the AIT that can be used in studies of self-other control processes.
Imitation; Automatic imitation; Controlled imitation; Mirror system; Motor resonance; Automatic imitation Task; Self-related processing; Other-related processing; Self-other control
Background. Normally one habituates rapidly to steady, faint sensations. People with sensory hypersensitivity (SH), by contrast, continue to attend to such stimuli and find them noxious. SH is common in Tourette syndrome (TS) and autism, and methods to quantify SH may lead to better understanding of these disorders. In an attempt to objectively quantify SH severity, the authors tested whether a choice reaction time (CRT) task was a sensitive enough measure to detect significant distraction from a steady tactile stimulus, and to detect significantly greater distraction in subjects with more severe SH.
Methods. Nineteen ambulatory adult volunteers with varying scores on the Adult Sensory Questionnaire (ASQ), a clinical measure of SH, completed a CRT task in the alternating presence and absence of tactile stimulation.
Results. Tactile stimulation interfered with attention (i.e., produced longer reaction times), and this effect was significantly greater in participants with more SH (higher ASQ scores). Accuracy on the CRT was high in blocks with and without stimulation. Habituation within stimulation blocks was not detected.
Conclusion. This approach can detect distraction from a cognitive task by a steady, faint tactile stimulus that does not degrade response accuracy. The method was also sensitive to the hypothesized enhancement of this effect by SH. These results support the potential utility of this approach to quantifying SH, and suggest possible refinements for future studies.
Attention; Sensory hypersensitivity; Habituation; Tourette syndrome; Reaction time; Tactile stimulation
To examine mirror neuron abnormalities in autism, high-functioning children with autism and matched controls underwent fMRI while imitating and observing emotional expressions. Although both groups performed the tasks equally well, children with autism showed no mirror neuron activity in the inferior frontal gyrus (pars opercularis). Notably, activity in this area was inversely related to symptom severity in the social domain, suggesting that a dysfunctional ‘mirror neuron system’ may underlie the social deficits observed in autism.
Parietal and premotor cortices of the macaque monkey contain distinct populations of neurons which, in addition to their motor discharge, are also activated by visual stimulation. Among these visuomotor neurons, a population of grasping neurons located in the anterior intraparietal area (AIP) shows discharge modulation when the own hand is visible during object grasping. Given the dense connections between AIP and inferior frontal regions, we aimed at investigating whether two hand-related frontal areas, ventral premotor area F5 and primary motor cortex (area F1), contain neurons with similar properties. Two macaques were involved in a grasping task executed in various light/dark conditions in which the to-be-grasped object was kept visible by a dim retro-illumination. Approximately 62% of F5 and 55% of F1 motor neurons showed light/dark modulations. To better isolate the effect of hand-related visual input, we introduced two further conditions characterized by kinematic features similar to the dark condition. The scene was briefly illuminated (i) during hand preshaping (pre-touch flash, PT-flash) and (ii) at hand-object contact (touch flash, T-flash). Approximately 48% of F5 and 44% of F1 motor neurons showed a flash-related modulation. Considering flash-modulated neurons in the two flash conditions, ∼40% from F5 and ∼52% from F1 showed stronger activity in PT- than T-flash (PT-flash-dominant), whereas ∼60% from F5 and ∼48% from F1 showed stronger activity in T- than PT-flash (T-flash-dominant). Furthermore, F5, but not F1, flash-dominant neurons were characterized by a higher peak and mean discharge in the preferred flash condition as compared to light and dark conditions. Still considering F5, the distribution of the time of peak discharge was similar in light and preferred flash conditions. This study shows that the frontal cortex contains neurons, previously classified as motor neurons, which are sensitive to the observation of meaningful phases of the own grasping action. We conclude by discussing the possible functional role of these populations.
Single-neuron recording; Grasping; Visuomotor; Frontal cortex
A growing body of evidence suggests that autism spectrum disorders (ASDs) are related to altered communication between brain regions. Here, we present findings showing that ASD is characterized by a pattern of reduced functional integration as well as reduced segregation of large-scale brain networks. Twenty-three children with ASD and 25 typically developing matched controls underwent functional magnetic resonance imaging while passively viewing emotional face expressions. We examined whole-brain functional connectivity of two brain structures previously implicated in emotional face processing in autism: the amygdala bilaterally and the right pars opercularis of the inferior frontal gyrus (rIFGpo). In the ASD group, we observed reduced functional integration (i.e., less long-range connectivity) between amygdala and secondary visual areas, as well as reduced segregation between amygdala and dorsolateral prefrontal cortex. For the rIFGpo seed, we observed reduced functional integration with parietal cortex and increased integration with right frontal cortex as well as right nucleus accumbens. Finally, we observed reduced segregation between rIFGpo and the ventromedial prefrontal cortex. We propose that a systems-level approach—whereby the integration and segregation of large-scale brain networks in ASD is examined in relation to typical development—may provide a more detailed characterization of the neural basis of ASD.
amygdala; connectivity; default mode network; face processing; mirror neuron system
The ability to process facial expressions can be modified by altering the spatial frequency of the stimuli, an effect that has been attributed to differential properties of visual pathways that convey different types of information to distinct brain regions at different speeds. While this effect suggests a potential influence of spatial frequency on the processing speed of facial emotion, this hypothesis has not been examined directly. We addressed this question using a facial emotion identification task with photographs containing either high spatial frequency (HSF), low spatial frequency (LSF), or broadband spatial frequency (BSF). Temporal processing of emotion perception was manipulated by suppressing visual perception with a single-pulse transcranial magnetic stimulation (TMS), delivered to the visual cortex at six intervals prior to (forward masking) or following (backward masking) stimulus presentation. Participants performed best in the BSF, followed by LSF, and finally HSF condition. A spatial frequency by forward/backward masking interaction effect demonstrated reduced performance in the forward masking component in the BSF condition and a reversed performance pattern in the HSF condition, with no significant differences between forward and backward masking in the LSF condition. Results indicate that LSF information may play a greater role than HSF information in emotional processing, but may not be sufficient for fast conscious perception of emotion. As both LSF and HSF filtering reduced the speed of extracting emotional information from faces, it is possible that intact BSF faces have an inherent perceptual advantage and hence benefit from faster temporal processing.
Affect perception; facial emotion; transcranial magnetic stimulation; visual masking
We used Support Vector Machine (SVM) to perform multivariate pattern classification based on brain activation during emotional processing in healthy participants with subclinical depressive symptoms. Six-hundred undergraduate students completed the Beck Depression Inventory II (BDI-II). Two groups were subsequently formed: (i) subclinical (mild) mood disturbance (n = 17) and (ii) no mood disturbance (n = 17). Participants also completed a self-report questionnaire on subclinical psychotic symptoms, the Community Assessment of Psychic Experiences Questionnaire (CAPE) positive subscale. The functional magnetic resonance imaging (fMRI) paradigm entailed passive viewing of negative emotional and neutral scenes. The pattern of brain activity during emotional processing allowed correct group classification with an overall accuracy of 77% (p = 0.002), within a network of regions including the amygdala, insula, anterior cingulate cortex and medial prefrontal cortex. However, further analysis suggested that the classification accuracy could also be explained by subclinical psychotic symptom scores (correlation with SVM weights r = 0.459, p = 0.006). Psychosis proneness may thus be a confounding factor for neuroimaging studies in subclinical depression.
Machine learning; Support vector machine; fMRI; Emotion; Subclinical depression; Psychosis proneness; Neuroimaging
Adolescence is marked by profound psychosocial and physiological changes. Although investigations into the interactions between these forces have begun to shed light on the neural correlates of affective processing during the transition to adolescence, relatively little is known about the relationship between pubertal development and emotion perception at the neural level. In the current longitudinal study, 45 neurotypical participants were shown affective facial displays while undergoing fMRI, at ages 10 and 13. Neural responses to emotional expressions at both time points were then correlated with a self-report measure of pubertal development, revealing positive associations with activity in amygdala, thalamus and visual cortical areas at age 10 that increased in magnitude and extent by age 13. At the latter time point, pubertal development was additionally correlated with enhanced responses to faces in temporal pole, ventrolateral prefrontal cortex (PFC) and dorsomedial PFC. Longitudinal comparisons revealed that the relationships between pubertal development and activity in the amygdala, hippocampus and temporal pole were significantly stronger during early adolescence than late childhood. These results suggest that pubertal development per se is linked to neural processing of socioemotional stimuli, particularly with respect to the integration of complex perceptual input and higher order cortical processing of affective content.
adolescence; puberty; emotion; fMRI; amygdala; longitudinal
Autism spectrum disorders (ASD) are characterized by significant social impairments, including deficits in orienting attention following social cues. Behavioral studies investigating social orienting in ASD, however, have yielded mixed results, as the use of naturalistic paradigms typically reveals clear deficits whereas computerized laboratory experiments often report normative behavior. The present study is the first to examine the neural mechanisms underlying social orienting in ASD in order to provide new insight into the social attention impairments that characterize this disorder. Using fMRI, we examined the neural correlates of social orienting in children and adolescents with ASD and in a matched sample of typically developing (TD) controls while they performed a spatial cueing paradigm with social (eye gaze) and nonsocial (arrow) cues. Cues were either directional (indicating left or right) or neutral (indicating no direction), and directional cues were uninformative of the upcoming target location in order to engage automatic processes by minimizing expectations. Behavioral results demonstrated intact orienting effects for social and nonsocial cues, with no differences between groups. The imaging results, however, revealed clear group differences in brain activity. When attention was directed by social cues compared to nonsocial cues, the TD group showed increased activity in frontoparietal attention networks, visual processing regions, and the striatum, whereas the ASD group only showed increased activity in the superior parietal lobule. Significant group × cue type interactions confirmed greater responsivity in task-relevant networks for social cues than nonsocial cues in TD as compared to ASD, despite similar behavioral performance. These results indicate that, in the autistic brain, social cues are not assigned the same privileged status as they are in the typically developing brain. These findings provide the first empirical evidence that the neural circuitry involved in social orienting is disrupted in ASD and highlight that normative behavioral performance in a laboratory setting may reflect compensatory mechanisms rather than intact social attention.
autism; attention; functional magnetic resonance imaging; gaze; social cue
The investigation of cultural phenomena using neuroscientific methods—cultural neuroscience (CN)—is receiving increasing attention. Yet it is unclear whether the integration of cultural study and neuroscience is merely additive, providing additional evidence of neural plasticity in the human brain, or truly synergistic, yielding discoveries that neither discipline could have achieved alone. We discuss how the parent fields to CN: cross-cultural psychology, psychological anthropology and cognitive neuroscience inform the investigation of the role of cultural experience in shaping the brain. Drawing on well-established methodologies from cross-cultural psychology and cognitive neuroscience, we outline a set of guidelines for CN, evaluate 17 CN studies in terms of these guidelines, and provide a summary table of our results. We conclude that the combination of culture and neuroscience is both additive and synergistic; while some CN methodologies and findings will represent the direct union of information from parent fields, CN studies employing the methodological rigor required by this logistically challenging new field have the potential to transform existing methodologies and produce unique findings.
cross-cultural; cross disciplinary; cultural-neuroscience; culture; neuroscience; neuroimaging
In the course of developing an atlas and reference system for the normal human brain throughout the human age span from structural and functional brain imaging data, the International Consortium for Brain Mapping (ICBM) developed a set of “normal” criteria for subject inclusion and the associated exclusion criteria. The approach was to minimize inclusion of subjects with any medical disorders that could affect brain structure or function. In the past two years, a group of 1,685 potential subjects responded to solicitation advertisements at one of the consortium sites (UCLA). Subjects were screened by a detailed telephone interview and then had an in-person history and physical examination. Of those who responded to the advertisement and considered themselves to be normal, only 31.6% (532 subjects) passed the telephone screening process. Of the 348 individuals who submitted to in-person history and physical examinations, only 51.7% passed these screening procedures. Thus, only 10.7% of those individuals who responded to the original advertisement qualified for imaging. The most frequent cause for exclusion in the second phase of subject screening was high blood pressure followed by abnormal signs on neurological examination. It is concluded that the majority of individuals who consider themselves normal by self-report are found not to be so by detailed historical interviews about underlying medical conditions and by thorough medical and neurological examinations. Recommendations are made with regard to the inclusion of subjects in brain imaging studies and the criteria used to select them.
While religious faith remains one of the most significant features of human life, little is known about its relationship to ordinary belief at the level of the brain. Nor is it known whether religious believers and nonbelievers differ in how they evaluate statements of fact. Our lab previously has used functional neuroimaging to study belief as a general mode of cognition , and others have looked specifically at religious belief . However, no research has compared these two states of mind directly.
We used functional magnetic resonance imaging (fMRI) to measure signal changes in the brains of thirty subjects—fifteen committed Christians and fifteen nonbelievers—as they evaluated the truth and falsity of religious and nonreligious propositions. For both groups, and in both categories of stimuli, belief (judgments of “true” vs judgments of “false”) was associated with greater signal in the ventromedial prefrontal cortex, an area important for self-representation , , , , emotional associations , reward , , , and goal-driven behavior . This region showed greater signal whether subjects believed statements about God, the Virgin Birth, etc. or statements about ordinary facts. A comparison of both stimulus categories suggests that religious thinking is more associated with brain regions that govern emotion, self-representation, and cognitive conflict, while thinking about ordinary facts is more reliant upon memory retrieval networks.
While religious and nonreligious thinking differentially engage broad regions of the frontal, parietal, and medial temporal lobes, the difference between belief and disbelief appears to be content-independent. Our study compares religious thinking with ordinary cognition and, as such, constitutes a step toward developing a neuropsychology of religion. However, these findings may also further our understanding of how the brain accepts statements of all kinds to be valid descriptions of the world.
There is evidence that the right hemisphere is involved in processing self-related stimuli. Previous brain imaging research has found a network of right-lateralized brain regions that preferentially respond to seeing one's own face rather than a familiar other. Given that the self is an abstract multimodal concept, we tested whether these brain regions would also discriminate the sound of one's own voice compared to a friend's voice. Participants were shown photographs of their own face and friend's face, and also listened to recordings of their own voice and a friend's voice during fMRI scanning. Consistent with previous studies, seeing one's own face activated regions in the inferior frontal gyrus (IFG), inferior parietal lobe and inferior occipital cortex in the right hemisphere. In addition, listening to one's voice also showed increased activity in the right IFG. These data suggest that the right IFG is concerned with processing self-related stimuli across multiple sensory modalities and that it may contribute to an abstract self-representation.
self; self-recognition; fMRI; face; voice
In lateralized simple reaction time (SRT) tasks with unimanual responses, reaction times (RTs) are faster with ipsilateral (uncrossed) than with contralateral (crossed) response hand- target hemifield combinations. The difference between crossed and uncrossed responses (CUD) is typically interpreted to reflect callosal transfer time. Indeed, split brain patients have much longer CUDs than control subjects. However, while many studies have supported the hypothesis that the CUD reflects callosal transmission time, a few studies have suggested that the CUD may be affected by non-anatomical factors. We investigated the nature of these inconsistent results in two experiments. In the first, we asked half of our subjects to cross their arms while performing the task. The CUD was not affected by arms crossing, supporting the anatomical model of the CUD. In the second experiment, however, all subjects were asked to cross their arms in half of the trials. In this experiment, arms crossing significantly affected the CUD, thus showing that spatial attention modulates the CUD. These latter results cannot be readily explained by a simple callosal relay interpretation of the CUD. Rather, the CUD seems to reflect a mix of anatomical and non-anatomical factors produced by task history. Thus, the seemingly inconsistent results of previous studies can be reconciled by taking into account differences in task history across studies.
Reaction time; Poffenberger paradigm; Interhemispheric transfer; Spatial attention; Task context
Autism is a developmental disorder characterized by decreased interest and engagement in social interactions and by enhanced self-focus. While previous theoretical approaches to understanding autism have emphasized social impairments and altered interpersonal interactions, there is a recent shift towards understanding the nature of the representation of the self in individuals with autism spectrum disorders (ASD). Still, the neural mechanisms subserving self-representations in ASD are relatively unexplored.
We used event-related fMRI to investigate brain responsiveness to images of the subjects' own face and to faces of others. Children with ASD and typically developing (TD) children viewed randomly presented digital morphs between their own face and a gender-matched other face, and made “self/other” judgments. Both groups of children activated a right premotor/prefrontal system when identifying images containing a greater percentage of the self face. However, while TD children showed activation of this system during both self- and other-processing, children with ASD only recruited this system while viewing images containing mostly their own face.
This functional dissociation between the representation of self versus others points to a potential neural substrate for the characteristic self-focus and decreased social understanding exhibited by these individuals, and suggests that individuals with ASD lack the shared neural representations for self and others that TD children and adults possess and may use to understand others.
Parallel processing of multiple sensory stimuli is critical for efficient, successful interaction with the environment. An experimental approach to studying parallel processing in sensorimotor integration is to examine reaction times to multiple copies of the same stimulus. Reaction times to bilateral copies of light flashes are faster than to single, unilateral light flashes. These faster responses may be due to ‘statistical facilitation’ between independent processing streams engaged by the two copies of the light flash. On some trials, however, reaction times are faster than predicted by statistical facilitation. This indicates that a neural ‘coactivation’ of the two processing streams must have occurred. Here we use fMRI to investigate the neural locus of this coactivation. Subjects responded manually to the detection of unilateral light flashes presented to the left or right visual hemifield, and to the detection of bilateral light flashes. We compared the bilateral trials where subjects' reaction times exceeded the limit predicted by statistical facilitation to bilateral trials that did not exceed the limit. Activity in the right temporo-parietal junction was higher in those bilateral trials that showed coactivation than in those that did not. These results suggest the neural coactivation observed in visuomotor integration occurs at a cognitive rather than sensory or motor stage of processing.
Self–other discrimination is fundamental to social interaction, however, little is known about the neural systems underlying this ability. In a previous functional magnetic resonance imaging study, we demonstrated that a right fronto-parietal network is activated during viewing of self-faces as compared with the faces of familiar others. Here we used image-guided repetitive transcranial magnetic stimulation (rTMS) to create a ’virtual lesion’ over the parietal component of this network to test whether this region is necessary for discriminating self-faces from other familiar faces. The current results indeed show that 1 Hz rTMS to the right inferior parietal lobule (IPL) selectively disrupts performance on a self–other discrimination task. Applying 1 Hz rTMS to the left IPL had no effect. It appears that activity in the right IPL is essential to the task, thus providing for the first time evidence for a causal relation between a human brain area and this high-level cognitive capacity.
self-awareness; self-recognition; social cognition; inferior parietal lobule; mirror neurons
It has been suggested that cortical neural systems for language evolved from motor cortical systems, in particular from those fronto-parietal systems responding also to action observation. While previous studies have shown shared cortical systems for action – or action observation - and language, they did not address the question of whether linguistic processing of visual stimuli occurs only within a subset of fronto-parietal areas responding to action observation. If this is true, the hypothesis that language evolved from fronto-parietal systems matching action execution and action observation would be strongly reinforced.
Methodology/ Principal Findings
We used functional magnetic resonance imaging (fMRI) while subjects watched video stimuli of hand-object-interactions and control photo stimuli of the objects and performed linguistic (conceptual and phonological), and perceptual tasks. Since stimuli were identical for linguistic and perceptual tasks, differential activations had to be related to task demands. The results revealed that the linguistic tasks activated left inferior frontal areas that were subsets of a large bilateral fronto-parietal network activated during action perception. Not a single cortical area demonstrated exclusive – or even simply higher - activation for the linguistic tasks compared to the action perception task.
These results show that linguistic tasks do not only share common neural representations but essentially activate a subset of the action observation network if identical stimuli are used. Our findings strongly support the evolutionary hypothesis that fronto-parietal systems matching action execution and observation were co-opted for language, a process known as exaptation.
People all over the world use their hands to communicate expressively. Autonomous gestures, also known as emblems, are highly social in nature, and convey conventionalized meaning without accompanying speech. To study the neural bases of cross-cultural social communication, we used single pulse transcranial magnetic stimulation (TMS) to measure corticospinal excitability (CSE) during observation of culture-specific emblems. Foreign Nicaraguan and familiar American emblems as well as meaningless control gestures were performed by both a Euro-American and a Nicaraguan actor. Euro-American participants demonstrated higher CSE during observation of the American compared to the Nicaraguan actor. This motor resonance phenomenon may reflect ethnic and cultural ingroup familiarity effects. However, participants also demonstrated a nearly significant (p = 0.053) actor by emblem interaction whereby both Nicaraguan and American emblems performed by the American actor elicited similar CSE, whereas Nicaraguan emblems performed by the Nicaraguan actor yielded higher CSE than American emblems. The latter result cannot be interpreted simply as an effect of ethnic ingroup familiarity. Thus, a likely explanation of these findings is that motor resonance is modulated by interacting biological and cultural factors.
Self–other discrimination is fundamental to social interaction, however, little is known about the neural systems underlying this ability. In a previous functional magnetic resonance imaging study, we demonstrated that a right fronto-parietal network is activated during viewing of self-faces as compared with the faces of familiar others. Here we used image-guided repetitive transcranial magnetic stimulation (rTMS) to create a ‘virtual lesion’ over the parietal component of this network to test whether this region is necessary for discriminating self-faces from other familiar faces. The current results indeed show that 1 Hz rTMS to the right inferior parietal lobule (IPL) selectively disrupts performance on a self–other discrimination task. Applying 1 Hz rTMS to the left IPL had no effect. It appears that activity in the right IPL is essential to the task, thus providing for the first time evidence for a causal relation between a human brain area and this high-level cognitive capacity.
self-awareness; self-recognition; social cognition; inferior parietal lobule; mirror neurons
The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype– phenotype–behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders.