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.

The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions. The combination of ABIDE I and ABIDE II provides investigators with 2156 unique cross-sectional datasets allowing selection of samples for discovery and/or replication. This sample size can also facilitate the identification of neurobiological subgroups, as well as preliminary examinations of sex differences in ASD. Additionally, ABIDE II includes a range of psychiatric variables to inform our understanding of the neural correlates of co-occurring psychopathology; 284 diffusion imaging datasets are also included. It is anticipated that these enhancements will contribute to unraveling key sources of ASD heterogeneity.

Autism spectrum disorders (ASD) are far more prevalent in males than in females. Little is known however about the differential neural expression of ASD in males and females. We used a resting-state fMRI-dataset comprising 42 males/ 42 females with ASD and 75 male/75 female typical-controls to examine whether autism-related alterations in intrinsic functional connectivity are similar or different in males and females, and particularly whether alterations reflect 'neural masculinization', as predicted by the Extreme Male Brain theory. Males and females showed a differential neural expression of ASD, characterized by highly consistent patterns of hypo-connectivity in males with ASD (compared to typical males), and hyper-connectivity in females with ASD (compared to typical females). Interestingly, patterns of hyper-connectivity in females with ASD reflected a shift towards the (high) connectivity levels seen in typical males (neural masculinization), whereas patterns of hypo-connectivity observed in males with ASD reflected a shift towards the (low) typical feminine connectivity patterns (neural feminization). Our data support the notion that ASD is a disorder of sexual differentiation rather than a disorder characterized by masculinization in both genders. Future work is needed to identify underlying factors such as sex hormonal alterations that drive these sex-specific neural expressions of ASD.

Folk psychology advocates the existence of gender differences in socio-cognitive functions such as ‘reading’ the mental states of others or discerning subtle differences in body-language. A female advantage has been demonstrated for emotion recognition from facial expressions, but virtually nothing is known about gender differences in recognizing bodily stimuli or body language. The aim of the present study was to investigate potential gender differences in a series of tasks, involving the recognition of distinct features from point light displays (PLDs) depicting bodily movements of a male and female actor. Although recognition scores were considerably high at the overall group level, female participants were more accurate than males in recognizing the depicted actions from PLDs. Response times were significantly higher for males compared to females on PLD recognition tasks involving (i) the general recognition of ‘biological motion’ versus ‘non-biological’ (or ‘scrambled’ motion); or (ii) the recognition of the ‘emotional state’ of the PLD-figures. No gender differences were revealed for a control test (involving the identification of a color change in one of the dots) and for recognizing the gender of the PLD-figure. In addition, previous findings of a female advantage on a facial emotion recognition test (the ‘Reading the Mind in the Eyes Test’ (Baron-Cohen, 2001)) were replicated in this study. Interestingly, a strong correlation was revealed between emotion recognition from bodily PLDs versus facial cues. This relationship indicates that inter-individual or gender-dependent differences in recognizing emotions are relatively generalized across facial and bodily emotion perception. Moreover, the tight correlation between a subject's ability to discern subtle emotional cues from PLDs and the subject's ability to basically discriminate biological from non-biological motion provides indications that differences in emotion recognition may - at least to some degree – be related to more basic differences in processing biological motion per se.

One of the main characteristics of Autism Spectrum Disorder (ASD) are problems with social interaction and communication. Here, we explored ASD-related alterations in ‘reading’ body language of other humans. Accuracy and reaction times were assessed from two observational tasks involving the recognition of ‘biological motion’ and ‘emotions’ from point-light displays (PLDs). Eye movements were recorded during the completion of the tests. Results indicated that typically developed-participants were more accurate than ASD-subjects in recognizing biological motion or emotions from PLDs. No accuracy differences were revealed on two control-tasks (involving the indication of color-changes in the moving point-lights). Group differences in reaction times existed on all tasks, but effect sizes were higher for the biological and emotion recognition tasks. Biological motion recognition abilities were related to a person’s ability to recognize emotions from PLDs. However, ASD-related atypicalities in emotion recognition could not entirely be attributed to more basic deficits in biological motion recognition, suggesting an additional ASD-specific deficit in recognizing the emotional dimension of the point light displays. Eye movements were assessed during the completion of tasks and results indicated that ASD-participants generally produced more saccades and shorter fixation-durations compared to the control-group. However, especially for emotion recognition, these altered eye movements were associated with reductions in task-performance.

Neurodevelopmental disconnections have been assumed to cause behavioral alterations in autism spectrum disorders (ASDs). Here, we combined measurements of intrinsic functional connectivity (iFC) from resting-state functional magnetic resonance imaging (fMRI) with task-based fMRI to explore whether altered activity and/or iFC of the right posterior superior temporal sulcus (pSTS) mediates deficits in emotion recognition in ASD. Fifteen adults with ASD and 15 matched-controls underwent resting-state and task-based fMRI, during which participants discriminated emotional states from point light displays (PLDs). Intrinsic FC of the right pSTS was further examined using 584 (278 ASD/306 controls) resting-state data of the Autism Brain Imaging Data Exchange (ABIDE). Participants with ASD were less accurate than controls in recognizing emotional states from PLDs. Analyses revealed pronounced ASD-related reductions both in task-based activity and resting-state iFC of the right pSTS with fronto-parietal areas typically encompassing the action observation network (AON). Notably, pSTS-hypo-activity was related to pSTS-hypo-connectivity, and both measures were predictive of emotion recognition performance with each measure explaining a unique part of the variance. Analyses with the large independent ABIDE dataset replicated reductions in pSTS-iFC to fronto-parietal regions. These findings provide novel evidence that pSTS hypo-activity and hypo-connectivity with the fronto-parietal AON are linked to the social deficits characteristic of ASD.

Several transcranial magnetic stimulation (TMS) studies have reported facilitation of the primary motor cortex (M1) during the mere observation of actions. This facilitation was shown to be highly congruent, in terms of somatotopy, with the observed action, even at the level of single muscles. With the present study, we investigated whether this muscle-specific facilitation of the observer's motor system reflects the degree of muscular force that is exerted in an observed action. Two separate TMS experiments are reported in which corticospinal excitability was measured in the hand area of M1 while subjects observed the lifting of objects of different weights. The type of action 'grasping-and-lifting-the-object' was always identical, but the grip force varied according to the object's weight. In accordance to previous findings, excitability of M1 was shown to modulate in a muscle-specific way, such that only the cortical representation areas in M1 that control the specific muscles used in the observed lifting action became increasingly facilitated. Moreover, muscle-specific M1 facilitation was shown to modulate to the force requirements of the observed actions, such that M1 excitability was considerably higher when observing heavy object lifting compared with light object lifting. Overall, these results indicate that different levels of observed grip force are mirrored onto the observer's motor system in a highly muscle-specific manner. The measured force-dependent modulations of corticospinal excitability in M1 are hypothesized to be functionally relevant for scaling the observed grip force in the observer's own motor system. In turn, this mechanism may contribute, at least partly, to the observer's ability to infer the weight of the lifted object.

Previous studies using transcranial magnetic stimulation (TMS) have shown that during the observation of actions performed by others, the observer's primary motor cortex (M1) becomes facilitated in a highly muscle specific fashion. Here, we used TMS to explore the effect of posture, perspective and body side on muscle specific facilitation of left M1. Subjects viewed video's showing left and right hand extension (palm-down) movements from a first person or third person perspective with their hand posture either congruent (palm-down) or incongruent (palm-up) to the posture of the observed model. Data indicated that facilitation of left M1 was substantially different for observing actions executed with the right (contralateral) or left (ipsilateral) hand. For right hand actions, facilitation of left M1 was shown to be highly specific to the muscle used in the observed action ('intrinsic mapping'). During the observation of left hand stimuli, only half of the subjects displayed this muscle specific facilitation, whereas in the other half, M1 was facilitated according to the observed movement direction ('extrinsic mapping'). Absolute effect magnitude was particularly high when right hand actions were observed from a first person perspective, whereas, for left hand actions, the third person perspective was more efficient. The degree of postural congruency between body parts of the observer and observed model only mildly influenced M1 facilitation. Since action observation is increasingly considered in rehabilitation therapies, the present findings may help identifying the most effective conditions for stimulating the motor system during action observation.