Longitudinal Changes in Functional Connectivity in Autism Spectrum Disorder

Background: Autism spectrum disorder (ASD) has consistently been linked to altered functional connectivity in the brain. However, there are conflicting results as to whether the autistic brain is characterized by increased or decreased connectivity. One recent theory argues that such discrepancies in the functional connectivity literature are due to an atypical developmental trajectory in ASD, as hyperconnectivitiy is more likely to be reported in studies focusing on children, and hypoconnectivity in studies focusing on adolescents or adults (Uddin et al., 2013). Evidence from structural brain connectivity and volumetric studies likewise support the possibility of an atypical developmental course from childhood through adulthood in ASD (Bakhtiari et al., 2012; Hua et al., 2013). However, all studies investigating the developmental trajectory of functional connectivity in ASD thus far have used cross-sectional samples. Yet longitudinal studies are crucial for better understanding how connectivity alterations in ASD may relate to age: longitudinal samples allow for greater sensitivity when mapping trajectories and comparing age groups, as well as greater confidence that age-dependent findings are not due to inherent differences between the subjects included in each age cohort

Objectives: Using a longitudinal sample, characterize how functional connectivity in key intrinsic connectivity networks (e.g. default mode network, DMN; salience network, SN) evolves from early- to late-adolescence in ASD relative to typical development, and investigate the extent to which observed patterns of atypical connectivity in ASD are age-dependent.

Methods: A total of 41 individuals completed a resting-state functional MRI scan in both early-adolescence and late-adolescence; the mean age at time point 1 was 12.74 + 0.92 years old, and the mean age at time point 2 was 15.8 + 0.93 years old. DMN functional connectivity was investigated using a seed located in the posterior cingulate cortex (PCC), and scrubbing was applied to reduce potential motion confounds (Power et al., 2012). Initial group comparisons, focusing on the DMN in a subset of these participants, were completed in FSL and prethresholded with a joint mask of the within group results. Connectivity z-scores were subsequently extracted from regions which displayed an effect of diagnosis and analyzed using a 2 (diagnosis) by 2 (time point) ANOVA.

Results: Both diagnostic groups displayed greater local connectivity with the PCC and angular gyrus in early-adolescence than in late-adolescence. Relative to the TD group, the ASD group displayed hyperconnectivity with the angular gyrus in early-adolescence, and hyperconnectivity of the PCC and medial prefrontal cortex in late adolescence. When extracting connectivity estimates, these regions displayed a significant interaction between diagnosis and time point such that the developmental trajectory of functional connectivity differed between the ASD and TD groups. Furthermore, the connectivity alterations present in ASD in early-adolescence were not present in late adolescence and vice versa when using this region-of-interest approach.

Conclusions: These initial results show distinct patterns of altered DMN connectivity during early vs. late adolescence, which may contribute to the age-dependence of atypical connectivity findings in ASD. Overall, these findings highlight the value of using a longitudinal design when assessing atypical developmental trajectories.