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

Abstract

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.

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Fig. 1

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Correspondence to Ralph-Axel Müller.

Ethics declarations

All procedures performed in studies involving human participants were in accordance with the ethical standards of the appropriate institutional research boards and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

This study was supported by the National Institutes of Health R01 MH081023 (PI: RAM), K01 MH097972 (PI: Inna Fishman), and IMSD R25GM058906.

Conflict of interest

All authors declare that they have no conflict of interest related to the study presented here.

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Supplementary Fig. 1

Surface renderings of regional homogeneity differences between ASD and TD groups for each subsample from analyses without global signal regression and with non-standardized KCC-Z ReHo values (a), and without GSR and with standardized KCC ReHo values (b). In all supplementary figures, the two columns on the left depict the left hemisphere and the two columns on the right depict the right hemisphere (p < .05, corrected).

High resolution image (TIFF 87857 kb)

Supplementary Fig. 2

Surface renderings for direct comparison of ReHo between eyes open and eyes closed cohorts for ASD and TD groups without GSR and with non-standardized KCC-Z ReHo values (a) and without GSR and with standardized KCC ReHo values (b).

High resolution image (TIFF 33839 kb)

Supplementary Fig. 3

Surface renderings of regional homogeneity differences between ASD and TD groups (a), and between ABIDE eyes open and eyes closed cohorts shown separately for ASD and TD groups (b) for multi-site subsamples (with site and head motion included as nuisance covariates).

High resolution image (TIFF 56561 kb)

Supplementary Fig. 4

Surface renderings of regional homogeneity differences between ASD and TD groups for each subsample, limiting inclusion to sites contributing ≥10 participants per group.

High resolution image (TIFF 33297 kb)

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Nair, S., Jao Keehn, R.J., Berkebile, M.M. et al. Local resting state functional connectivity in autism: site and cohort variability and the effect of eye status. Brain Imaging and Behavior 12, 168–179 (2018). https://doi.org/10.1007/s11682-017-9678-y

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Keywords

  • Autism spectrum disorder
  • Functional MRI
  • Local connectivity
  • Cingulate gyrus
  • Visual cortex
  • Default mode network