Kaat Alaerts

The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism

Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although 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) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 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 male subjects with ASDs and 403 male age-matched TCs. 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, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.

Force requirements of observed object lifting are encoded by the observer’s motor system: a TMS study

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.

Action and emotion recognition from point light displays: an investigation of gender differences.

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 subjects ability to discern subtle emotional cues from PLDs and the subjects 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.

Is the human primary motor cortex activated by muscular or direction-dependent features of observed movements?

Previous Transcranial Magnetic Stimulation (TMS) studies have shown that the observers motor system is facilitated by the sole observation of motor actions. However, it has not been possible so far to decide whether the observers motor system resonates primarily with the observed movement direction or the observed muscle activity, as both factors usually co-varied in these action observation studies. Here, we applied TMS to the wrist extensor and flexor during the observation of wrist motions such that the posture of the observer and the model in the video were either congruent or incongruent. Due to this manipulation, it was possible to disentangle whether the observers primary motor cortex (M1) is facilitated in accordance to either the observed movement direction or the observed muscle activation. Findings revealed that M1 resonated predominantly according to muscle-specific rather than direction-specific parameters of observed movements. More specifically, muscle-specific facilitation was maximal during congruent postures and remained evident, even though to a lower extent, during incongruent postures in which muscle activation and movement direction parameters were discordant. Our findings support the hypothesis that M1 contributes to action observation, by representing the observed movement in intrinsic, muscle-related coordinates. This transformation from extrinsic to intrinsic coordinates might be an important prerequisite for action understanding and imitation. Additionally, our data offer a neurophysiological explanation for interference that emerges when an action is performed while an incongruent action is observed.

Recognizing Biological Motion and Emotions from Point-Light Displays in Autism Spectrum Disorders

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.

Underconnectivity of the superior temporal sulcus predicts emotion recognition deficits in autism

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.

Changes in corticomotor excitability following prolonged muscle tendon vibration

The present experiment addressed whether increases in corticospinal excitability following sensory stimulation with muscle tendon vibration are accompanied by reorganization of the forearm musculature representation within the primary motor cortex. Using transcranial magnetic stimulation, we mapped the corticomotor projection to the dominant flexor carpi radialis (FCR) and extensor carpi radialis brevis (ECR) muscle before and after interventional sensory stimulation obtained via muscle tendon vibration (80Hz, 60 min) to the dominant distal wrist flexor tendons. Following vibration, MEP amplitude at the optimal stimulation position, motor output area, as well as map volume, increased significantly for the ECR. None of these effects reached significance for the FCR. These results suggest that the antagonistic vibratory response (AVR), which is considered to be of cortical origin, induces a delayed facilitation of musculature that is antagonistic to the site of the directly activated Ia afferent pathways. This example demonstrates that peripheral sensory stimulation can induce lasting increases in corticospinal excitability in the absence of actual movements.

Observing how others lift light or heavy objects: time-dependent encoding of grip force in the primary motor cortex

During movement observation, corticomotor excitability of the observer’s primary motor cortex (M1) is modulated according to the force requirements of the observed action. Here, we explored the time course of observation-induced force encoding. Force-related changes in M1-excitability were assessed by delivering transcranial magnetic stimulations at distinct temporal phases of an observed reach–grasp–lift action. Temporal changes in force-related electromyographic activity were also assessed during active movement execution. In observation conditions in which a heavy object was lifted, M1-excitability was higher compared to conditions in which a light object was lifted. Both during observation and execution, differential force encoding tended to gradually increase from the grasping phase until the late lift phase. Surprisingly, however, during observation, force encoding was already present at the early reach phase: a time point at which no visual cues on the object’s weight were available to the observer. As the observer was aware that the same weight condition was presented repeatedly, this finding may indicate that prior predictions concerning the upcoming weight condition are reflected by M1 excitability. Overall, findings may provide indications that the observer’s motor system represents motor predictions as well as muscular requirements to infer the observed movement goal.

Enhancing studies of the connectome in autism using the autism brain imaging data exchange II

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.

Corticospinal Facilitation Following Prolonged Proprioceptive Stimulation by Means of Passive Wrist Movement

The purpose of this study was to evaluate the delayed effects of repetitive sensory stimulation with passive wrist movement on corticospinal excitability of the forearm and hand musculature. Motor evoked potential responses to single and double pulse transcranial magnetic stimulation were recorded from the flexor carpi radialis, extensor carpi radialis, and the first dorsal interosseous muscles of the right limb. Data were collected before and after a 1 hour session of passive wrist movement (intervention group, n = 11) or after a same period of rest (control group, n = 9). Motor evoked potential size and area were analyzed to evaluate corticospinal excitability and short interval intracortical inhibition and facilitation. Training with passive movement resulted in a prolonged increase in corticospinal excitability in the flexor carpi radialis and extensor carpi radialis (until at least 1 hour postintervention), but did not evoke significant changes in the levels of short interval intracortical inhibition and facilitation. No such effects were noted in the control group or first dorsal interosseous muscle. Prolonged proprioceptive stimulation with passive wrist movement induces a delayed increase in corticospinal excitability of the forearm muscles. Accordingly, this intervention may promote motor cortical reorganization in the targeted muscles. Results show induced effects from passive movement training that may prove useful for neurorehabilitation therapies.