Evaluation of Differences in Temporal Synchrony Between Brain Regions in Individuals With Autism and Typical Development

Importance: Despite reports of widespread but heterogenous atypicality of functional connectivity in individuals with autism, little is known regarding the temporal dynamics of functional brain connections and how this relates to autistic traits. Objective: To investigate differences in temporal synchrony between brain regions in individuals with autism and typical development. Design: Cohort and replication sample study. The cohort includes data acquired between December 2016 and April 2018. Aggregate data included in the replication sample were released to the public in August 2012 (ABIDE I) and June 2016 (ABIDE II). Data were analyzed in April 2018. Setting: Population-based study conducted at the University of Utah. Participants: This cohort study, conducted at the University of Utah, included 90 adolescent and adult male participants. A larger sample from the multisite Autism Brain Imaging Data Exchange (ABIDE) was also used as a replication sample. Main Outcomes and Measures: Long duration (30 minutes per subject) of multiband, multi-echo functional magnetic resonance imaging was acquired in order to estimate functional connectivity between brain regions. Sustained connectivity, a measure of functional connectivity duration, as well as lagged temporal dynamics related to functional connectivity, were compared between groups for 361 gray matter regions of interest and a 17-network parcellation. Lagged findings were replicated in the larger ABIDE sample (n=1402). Sustained connectivity findings were also associated with behavioral and cognitive variables. Results: In 52 individuals with autism (mean [SD] age, 27.73 [8.66] years) and 38 controls (mean [SD] age, 27.09 [7.49] years), increases in both sustained connectivity and functional connectivity at several lags were found in individuals with autism compared to controls. Group differences in functional connectivity were replicated in the larger ABIDE dataset at a six second lag. Measures of symptom severity in individuals with autism were positively associated with sustained connectivity values. In controls, sustained connectivity was negatively associated with cognitive processing. Conclusions and Relevance: Whereas the magnitude of functional connectivity in autism is variable across brain regions, participant samples, and development, prolonged temporal synchrony of functional connections is reproducibly observed in autism, suggesting a potential mechanism for core symptoms.