Local resting state functional connectivity in autism: site and cohort variability and the effect of eye status

Sangeeta Nair, R. Joanne Jao Keehn, Michael M. Berkebile, José Omar Maximo, Natalia Witkowska, Ralph-Axel Müller

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with prominent impairments in sociocommunicative abilities, which have been linked to anomalous brain network organization. Despite ample evidence of atypical long-distance connectivity, the literature on local connectivity remains small and divergent. We used resting-state functional MRI regional homogeneity (ReHo) as a local connectivity measure in comparative analyses across several well-matched low-motion subsamples from the Autism Brain Imaging Data Exchange and in-house data, with a grand total of 147 ASD and 184 typically developing (TD) participants, ages 7-18 years. We tested for group differences in each subsample, with additional focus on the difference between eyes-open and eyes-closed resting states. Despite selection of highest quality data and tight demographic and motion matching between groups and across samples, few effects in exactly identical loci (voxels) were found across samples. However, there was gross consistency across all eyes-open samples of local overconnectivity (ASD > TD) in posterior, visual regions. There was also gross consistency of local underconnectivity (ASD < TD) in cingulate gyrus, although exact loci varied between mid/posterior and anterior sections. While all eyes-open datasets showed the described gross similarities, the pattern of group differences for participants scanned with eyes closed was different, with local overconnectivity in ASD in posterior cingulate gyrus, but underconnectivity in some visual regions. Our findings suggest that fMRI local connectivity measures may be relatively susceptible to site and cohort variability and that some previous inconsistencies in the ASD ReHo literature may be reconciled by more careful consideration of eye status.