Altered Development of the Hurst Exponent in the Medial Prefrontal Cortex in Preschoolers With Autism

Atypical balance of excitation (E) and inhibition (I) in the brain is thought to contribute to the emergence and symptomatology of autism spectrum disorder (ASD). E/I ratio can be estimated from resting-state functional magnetic resonance imaging (fMRI) using the Hurst exponent, H. A recent study reported decreased ventromedial prefrontal cortex (vmPFC) H in male adults with ASD. Part of the default mode network (DMN), the vmPFC plays an important role in emotion regulation, decision making, and social cognition. It frequently shows altered function and connectivity in individuals with autism.

The current study presents the first fMRI evidence of altered early development of vmPFC H and its link to DMN functional connectivity and emotional control in toddlers and preschoolers with ASD. A total of 83 children (45 with ASD), ages 1.5-5 years, underwent natural sleep fMRI as part of a longitudinal study.

In a cross-sectional analysis, vmPFC H decreased with age in children with ASD, reflecting increasing E/I ratio, but not in typically developing children. This effect remained significant when controlling for gestational age at birth, socioeconomic status, or ethnicity. The same pattern was also observed in a subset of children with longitudinal fMRI data acquired 2 years apart on average. Lower vmPFC H was also associated with reduced functional connectivity within the DMN as well as with higher emotional control deficits (although only significant transdiagnostically).

These results suggest an early onset of E/I imbalances in the vmPFC in ASD, with likely consequences for the maturation of the DMN.