Autism spectrum disorders (ASD) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, life-long nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. While the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE) – a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) datasets with corresponding structural MRI and phenotypic information from 539 individuals with ASD and 573 age-matched typical controls (TC; 7–64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 males with ASD and 403 male age-matched TC. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo and hyperconnectivity in the ASD literature; both were detected, though hypoconnectivity dominated, particularly for cortico-cortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASD (mid and posterior insula, posterior cingulate cortex), and highlighted less commonly explored regions such as thalamus. The survey of the ABIDE R-fMRI datasets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international datasets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.

Although the neurobiology of autism has been studied for more than two decades, the majority of these studies have examined brain structure 10, 20, or more years after the onset of clinical symptoms. The pathological biology that causes autism remains unknown, but its signature is likely to be most evident during the first years of life when clinical symptoms are emerging. This review highlights neurobiological findings during the first years of life and emphasizes early brain overgrowth as a key factor in the pathobiology of autism. We speculate that excess neuron numbers may be one possible cause of early brain overgrowth and produce defects in neural patterning and wiring, with exuberant local and short-distance cortical interactions impeding the function of large-scale, long-distance interactions between brain regions. Because large-scale networks underlie socio-emotional and communication functions, such alterations in brain architecture could relate to the early clinical manifestations of autism. As such, autism may additionally provide unique insight into genetic and developmental processes that shape early neural wiring patterns and make possible higher-order social, emotional, and communication functions.

Psychiatric and neurological disorders have historically provided key insights into the structure-function relationships that subserve human social cognition and behavior, informing the concept of the ‘social brain’. In this review, we take stock of the current status of this concept, retaining a focus on disorders that impact social behavior. We discuss how the social brain, social cognition, and social behavior are interdependent, and emphasize the important role of development and compensation. We suggest that the social brain, and its dysfunction and recovery, must be understood not in terms of specific structures, but rather in terms of their interaction in large-scale networks.

Several regions of the brain (including medial prefrontal cortex, rostral anterior cingulate, posterior cingulate, and precuneus) are known to have high metabolic activity during rest, which is suppressed during cognitively demanding tasks. With functional magnetic resonance imaging (fMRI), this suppression of activity is observed as ''deactivations,'' which are thought to be indicative of an interruption of the mental activity that persists during rest. Thus, measuring deactivation provides a means by which restassociated functional activity can be quantitatively examined. Applying this approach to autism, we found that the autism group failed to demonstrate this deactivation effect. Furthermore, there was a strong correlation between a clinical measure of social impairment and functional activity within the ventral medial prefrontal cortex. We speculate that the lack of deactivation in the autism group is indicative of abnormal internally directed processes at rest, which may be an important contribution to the social and emotional deficits of autism.default mode ͉ functional MRI ͉ introspection ͉ medial prefrontal cortex ͉ precuneus I nternally directed processes, such as self-reflective thought and most higher-order social and emotional processes, consistently activate a medial cortical network involving several brain regions, namely, the medial prefrontal cortex (MPFC) and adjacent rostral anterior cingulate cortex (rACC), posterior cingulate cortex (PCC), and precuneus (PrC) (1-4). Interestingly, this network is active when normal subjects are passively resting (5), leading many to speculate that these internally directed thoughts dominate the resting state (6-9). Self-reports from subjects while at rest further support this interpretation, wherein they typically describe ''autobiographical reminiscences, either recent or ancient, consisting of familiar faces, scenes, dialogues, stories, and melodies'' (8). Conversely, activity in this midline ''resting network'' is reduced when subjects perform externally directed, attention-demanding, goal-oriented tasks (such as the Stroop task or math calculations), and the resulting ''deactivation'' of this network is thought to be an indicator of an interruption of ongoing internally directed thought processes (5, 6, 9-11). In this context, the term deactivation simply refers to activity that is greater during rest than during task performance (i.e., the opposite of the more typically reported activations). Thus, an objective method for testing the functioning of this midline resting network is to measure whether there is deactivation in these regions during externally directed tasks as compared with passive rest. Similar approaches of examining this ''deactivation effect'' have been used in studies of patients with fragile X (12), a developmental disorder with some characteristics that overlap with autism, and in patients with dementia of the Alzheimer type (13) and Alzheimer's disease (14).There are several lines of evidence that suggest that this resting network m...