Recently, carriers of a common variant in the autism risk gene, CNTNAP2, were found to have altered functional brain connectivity using functional MRI. Here we scanned 328 young adults with high-field (4-Tesla) diffusion imaging, to test the hypothesis that carriers of this gene variant would have altered structural brain connectivity. All participants (209 females, 119 males, age: 23.4 +/−2.17 SD years) were scanned with 105-gradient high angular diffusion imaging (HARDI) at 4 Tesla. After performing a whole-brain fiber tractography using the full angular resolution of the diffusion scans, 70 cortical surface-based regions of interest were created from each individual’s co-registered anatomical data to compute graph metrics for all pairs of cortical regions. In graph theory analyses, subjects homozygous for the risk allele (CC) had lower characteristic path length, greater small-worldness and global efficiency in whole brain analyses, as well as greater eccentricity (maximum path length) in 60 of 70 nodes in regional analyses. These results were not reducible to differences in more commonly studied traits such as fiber density or fractional anisotropy. This is the first study to link graph theory metrics of brain structural connectivity to a common genetic variant linked with autism and will help us understand the neurobiology of circuits implicated in risk for autism.

Development of syntactic processing was examined to evaluate maturational processes including left language lateralization functions and increased specialization of brain regions important for syntactic processing. We utilized multimodal methods, including indices of brain activity from fMRI during a syntactic processing task, cortical thickness measurements from structural MRI, and neuropsychological measures. To evaluate hypotheses about increasing lateralization and specialization with development, we examined relationships between cortical thickness and magnitude and spatial activation extent within the left inferior frontal gyrus (IFG) and its right hemisphere homologue. We predicted that increased activation in the left and decreased activation in the right IFG would be associated with increased syntactic proficiency. As predicted, a more mature pattern of increased thickness in the right pars triangularis was associated with decreased activation intensity and extent in the right IFG. These findings suggest a maturational shift towards decreased involvement of the right IFG for syntactic processing. Better syntactic skills were associated with increased activation in the left IFG independent from age, suggesting increased specialization of the left IFG with increased proficiency. Overall, our findings show relationships between structural and functional neurodevelopment that co-occur with improved syntactic processing in critical language regions of the IFG in typically developing children.

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.

Peer rejection is particularly pervasive among adolescents with autism spectrum disorders (ASD). However, how adolescents with ASD differ from typically developing adolescents in their responses to peer rejection is poorly understood. The goal of the current investigation was to examine neural responses to peer exclusion among adolescents with ASD compared to typically developing adolescents. Nineteen adolescents with ASD and 17 typically developing controls underwent fMRI as they were ostensibly excluded by peers during an online game called Cyberball. Afterwards, participants reported their distress about the exclusion. Compared to typically developing adolescents, those with ASD displayed less activity in regions previously linked with the distressing aspect of peer exclusion, including the subgenual anterior cingulate and anterior insula, as well as less activity in regions previously linked with the regulation of distress responses during peer exclusion, including the ventrolateral prefrontal cortex and ventral striatum. Interestingly, however, both groups self-reported equivalent levels of distress. This suggests that adolescents with ASD may engage in differential processing of social experiences at the neural level, but be equally aware of, and concerned about, peer rejection. Overall, these findings contribute new insights about how this population may differentially experience negative social events in their daily lives.

Extensive developmental research has linked peer rejection during adolescence with a host of psychopathological outcomes, including depression. Moreover, recent neuroimaging research has suggested that increased activity in the subgenual region of the anterior cingulate cortex (subACC), which has been consistently linked with depression, is related to heightened sensitivity to peer rejection among adolescents. The goal of the current study was to directly test the hypothesis that adolescents’ subACC responses are predictive of their risk for future depression, by examining the relationship between subACC activity during peer rejection and increases in depressive symptoms during the following year. During a functional magnetic resonance imaging scan, 20 13-year-olds were ostensibly excluded by peers during an online social interaction. Participants’ depressive symptoms were assessed via parental reports at the time of the scan and 1 year later. Region of interest and whole-brain analyses indicated that greater subACC activity during exclusion was associated with increases in parent-reported depressive symptoms during the following year. These findings suggest that subACC responsivity to social exclusion may serve as a neural marker of adolescents’ risk for future depression and have implications for understanding the relationship between sensitivity to peer rejection and the increased risk of depression that occurs during adolescence.

Abnormal eye contact is a core symptom of autism spectrum disorders (ASD), though little is understood of the neural bases of gaze processing in ASD. Competing hypotheses suggest that individuals with ASD avoid eye contact due to the anxiety-provoking nature of direct eye gaze or that eye-gaze cues hold less interest or significance to children with ASD. The current study examined the effects of gaze direction on neural processing of emotional faces in typically developing (TD) children and those with ASD. While undergoing functional magnetic resonance imaging (fMRI), 16 high-functioning children and adolescents with ASD and 16 TD controls viewed a series of faces depicting emotional expressions with either direct or averted gaze. Children in both groups showed significant activity in visual-processing regions for both direct and averted gaze trials. However, there was a significant group by gaze interaction such that only TD children showed reliably greater activity in ventrolateral prefrontal cortex for direct versus averted gaze. The ASD group showed no difference between direct and averted gaze in response to faces conveying negative emotions. These results highlight the key role of eye gaze in signaling communicative intent and suggest altered processing of the emotional significance of direct gaze in children with ASD.