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. 2018 Nov 2;1(7):e184777.
doi: 10.1001/jamanetworkopen.2018.4777.

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

Jace B King  1   2 , Molly B D Prigge  3   4 , Carolyn K King  1   3 , Jubel Morgan  1   3   4 , Douglas C Dean 3rd  4 , Abigail Freeman  4   5 , Joaquin Alfonso M Villaruz  4 , Karen L Kane  4   5 , Erin D Bigler  6 , Andrew L Alexander  4   5   7 , Nicholas Lange  8 , Brandon A Zielinski  3   9 , Janet E Lainhart  4   5 , Jeffrey S Anderson  1   2   10
Affiliations

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

Jace B King et al. JAMA Netw Open. .

Abstract

Importance: Despite reports of widespread but heterogeneous atypicality of functional connectivity in individuals with autism, little is known regarding the temporal dynamics of functional brain connections and how they relate to autistic traits.

Objective: To investigate differences in temporal synchrony between brain regions in individuals with autism and those with typical development.

Design, setting, and 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. The study 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 analysis were conducted between January 2018 and April 2018.

Exposures: Male individuals diagnosed as having autism (n = 52) and typically developing male individuals (n = 38).

Main outcomes and measures: Long duration (30 minutes/individual) of multiband, multiecho functional magnetic resonance imaging was acquired 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 males with autism (mean [SD] age, 27.73 [8.66] years) and 38 control males with typical development (mean [SD] age, 27.09 [7.49] years), increases in both sustained and functional connectivity at several lags were found in individuals with autism compared with the control group. Group differences in functional connectivity were replicated in the larger ABIDE data set at a 6-second lag. Measures of symptom severity in individuals with autism were positively associated with sustained connectivity values. In the control group, sustained connectivity was negatively associated with cognitive processing. A replication sample (n = 1402) composed of 579 individuals with autism (80 female and 499 male; mean [SD] age, 15.08 [6.89] years) and 823 in the control group (211 female and 612 male; mean [SD] age, 15.06 [6.79] years) from the ABIDE data set was also analyzed.

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Alexander reports grants from the National Institutes of Health during the conduct of the study; and is part owner of Thervoyant, Inc outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Sustained Connectivity Is Significantly Increased in Individuals With Autism
Distribution of increased sustained connectivity values in individuals with autism relative to those in the control group across a 17-network parcellation (false discovery rate [FDR]–adjusted P < .05) (A) and across 361 gray matter regions of interest (ROIs) (uncorrected, P < .05) (B). DMN indicates Default Mode Network.
Figure 2.
Figure 2.. Aberrant Lagged-Based Functional Connectivity in Individuals With Autism
A, Comparison of averaged whole-brain functional connectivity between individuals with autism and those in the control group across −20 to +20 lags. Error bars represent standard error values. The asterisks represent between-group differences significant after false discovery rate correction (q[FDR] < .05). B, Distribution of increased functional connectivity in individuals with autism relative to controls at lag 4 (−6.212 seconds) across a 17-network parcellation (q[FDR] < .05) and across 361 gray matter regions of interest (ROIs) (q[FDR] < .05). ASD indicates autism spectrum disorder; DMN, default mode network; and TD, typically developing.
Figure 3.
Figure 3.. Aberrant Lagged-Based Functional Connectivity in Individuals With Autism in a Replication Sample
A, Distribution of decreased functional connectivity in individuals with autism relative to controls at 0 lag across a 17-network parcellation (false discovery rate correction, q[FDR] < .05) and across 361 gray matter regions of interest (ROIs) (uncorrected, P < .05). B, Distribution of increased functional connectivity in individuals with autism relative to those in the control group at a 6-second lag across a 17-network parcellation (q[FDR] < .05) and across 361 gray matter ROIs (uncorrected, P < .05). ABIDE indicates Autism Brain Imaging Data Exchange; DMN, default mode network.
See this image and copyright information in PMC

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