Autism spectrum disorders (ASDs) are neurodevelopmental disorders associated with atypical brain connectivity. Although language abilities vary widely, they are impaired or atypical in most children with ASDs. Underlying brain mechanisms, however, are not fully understood. The present study examined intrinsic functional connectivity (iFC) of the extended language network in a cohort of 52 children and adolescents with ASDs (ages 8-18 years), using restingstate functional magnetic resonance imaging. We found that, in comparison to typically developing peers (n = 50), children with ASDs showed increased connectivity between some language regions. In addition, seed-to-whole brain analyses revealed increased connectivity of language regions with posterior cingulate cortex (PCC) and visual regions in the ASD group. Post hoc effective connectivity analyses revealed a mediation effect of PCC on the iFC between bilateral inferior frontal and visual regions in an ASD subgroup. This finding qualifies and expands on previous reports of recruitment of visual areas in language processing in ASDs. In addition, increased iFC between PCC and visual regions was linked to lower language scores in this ASD subgroup, suggesting that increased connectivity with visual cortices, mediated by default mode regions, may be detrimental to language abilities.Lay Summary: We examined the functional connectivity between regions of the language network in children with autism spectrum disorders (ASDs) compared to typically developing peers. We found connectivity to be intact between core language in the ASD group, but also showed abnormally increased connectivity between regions of an extended language network. Additionally, connectivity was increased with regions associated with brain networks responsible for self-reflection and visual processing.

Background Prescription of psychotropic medications is common in autism spectrum disorders (ASDs), either off-label or to treat comorbid conditions such as ADHD or depression. Psychotropic medications are intended to alter brain function. Yet, studies investigating the functional brain organization in ASDs rarely take medication usage into account. This could explain some of the inconsistent findings of atypical brain network connectivity reported in the autism literature. Methods The current study tested whether functional connectivity patterns, as assessed with functional magnetic resonance imaging (fMRI), differed in a cohort of 49 children and adolescents with ASDs based on psychotropic medication status, and in comparison with 50 matched typically developing (TD) participants. Twenty-five participants in the ASD group (51%) reported current psychotropic medication usage, including stimulants, antidepressants, antipsychotics, and anxiolytics. Age, IQ, head motion, and ASD symptom severity did not differ between groups. Whole-brain functional connectivity between 132 regions of interest was assessed. Results Different functional connectivity patterns were identified in the ASD group taking psychotropic medications (ASD-on), as compared to the TD group and the ASD subgroup not using psychotropic medications (ASD-none). The ASD-on group showed distinct underconnectivity between the cerebellum and basal ganglia but cortico-cortical overconnectivity compared to the TD group. Cortical underconnectivity relative to the TD pattern, on the other hand, was pronounced in the ASD-none group. Conclusions These results suggest that psychotropic medications may affect functional connectivity, and that medication status should be taken into consideration when studying brain function in autism.

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Neuroimaging studies have revealed atypical activation during language and executive tasks in individuals with autism spectrum disorders (ASD). However, the spatiotemporal stages of processing associated with these dysfunctions remain poorly understood. Using an anatomically constrained magnetoencephalography approach, we examined event-related theta oscillations during a double-duty lexical decision task that combined demands on lexico-semantic processing and executive functions. Relative to typically developing peers, high-functioning adolescents with ASD had lower performance accuracy on trials engaging selective semantic retrieval and cognitive control. They showed an early overall theta increase in the left fusiform cortex followed by greater activity in the left-lateralized temporal (starting at ~250 ms) and frontal cortical areas (after ~450 ms) known to contribute to language processing. During response preparation and execution, the ASD group exhibited elevated theta in the anterior cingulate cortex, indicative of greater engagement of cognitive control. Simultaneously increased activity in the ipsilateral motor cortex may reflect a less lateralized and suboptimally organized motor circuitry. Spanning early sensory-specific and late response selection stages, the higher event-related theta responsivity in ASD may indicate compensatory recruitment to offset inefficient lexico-semantic retrieval under cognitively demanding conditions. Together, these findings provide further support for atypical language and executive functions in high-functioning ASD.

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Autism spectrum disorder (ASD) is highly heterogeneous in etiology and clinical presentation. Findings on intrinsic functional connectivity (FC) or task-induced FC in ASD have been inconsistent including both over- and underconnectivity and diverse regional patterns. As FC patterns change across different cognitive demands, a novel and more comprehensive approach to network architecture in ASD is to examine the change in FC patterns between rest and task states, referred to as reconfiguration. This approach is suitable for investigating inefficient network connectivity that may underlie impaired behavioral functioning in clinical disorders. We used functional magnetic resonance imaging (fMRI) to examine FC reconfiguration during lexical processing, which is often affected in ASD, with additional focus on interindividual variability. Thirty adolescents with ASD and a matched group of 23 typically developing (TD) participants completed a lexicosemantic decision task during fMRI, using multiecho-multiband pulse sequences with advanced BOLD signal sensitivity and artifact removal. Regions of interest (ROIs) were selected based on task-related activation across both groups, and FC and reconfiguration were compared between groups. The ASD group showed increased interindividual variability and overall greater reconfiguration than the TD group. An ASD subgroup with typical performance accuracy (at the level of TD participants) showed reduced similarity and typicality of FC during the task. In this ASD subgroup, greater FC reconfiguration was associated with increased language skills. Findings suggest that intrinsic functional networks in ASD may be inefficiently organized for lexicosemantic decisions and may require greater reconfiguration during task processing, with high performance levels in some individuals being achieved through idiosyncratic mechanisms.HighlightsFC reconfiguration is a comprehensive approach to examining network architectureFunctional networks are inefficiently organized for lexicosemantic decisions in ASDASD may require greater reconfiguration during task processingSome ASD individuals achieve high performance through idiosyncratic mechanisms