Altered intrinsic brain activity and connectivity in unaffected parents of individuals with autism spectrum disorder: a resting-state fMRI study

Objectives: Autism spectrum disorder (ASD) is a juvenile onset neurodevelopmental disorder with social impairment and stereotyped behavior as the main symptoms. Unaffected relatives may also exhibit similar ASD features due to genetic factors. Although previous studies have demonstrated atypical brain morphological features as well as task-state brain function abnormalities in unaffected parents with ASD children, it remains unclear the pattern of brain function in the resting state. Methods: A total of 42 unaffected parents of ASD children (pASD) and 39 age-, sex-, and handedness-matched controls were enrolled. Multiple resting-state fMRI (rsfMRI) analyzing methods were applied, including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC), to reveal the functional abnormalities of unaffected parents in ASD-related brain regions. Spearman Rho correlation analysis between imaging metric values and the severity of ASD traits were evaluated as well. Results: ALFF, ReHo, and DC methods all revealed abnormal brain regions in the pASD group, such as the left medial orbitofrontal cortex (mOFC) and rectal gyrus (ROI-1), bilateral supplementary motor area (ROI-2), right caudate nucleus head and right amygdala/para-hippocampal gyrus (ROI-3). FC decreasing was observed between ROI-1 and right anterior cingulate cortex (ACC), ROI-2, and bilateral precuneus. FC enhancing was observed between ROI-3 and right anterior cerebellar lobe, left medial temporal gyrus, left superior temporal gyrus, left medial frontal gyrus, left precentral gyrus, right postcentral gyrus in pASD. In addition, ALFF values in ROI-1, DC values in ROI-3 were positively correlated with AQ scores in pASD (ρ(1) = 0.298, P(1) = 0.007; ρ(2) = 0.220, P(2) = 0.040), while FC values between ROI-1 and right ACC were negatively correlated with AQ scores (ρ(3) = −0.334, P(3) = 0.002). Conclusion: rsfMRI metrics could be used as biomarkers to reveal the underlying neurobiological feature of ASD for unaffected parents.