Intrinsic excitation inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women
Excitation inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex related mechanisms (e.g. X linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in silico modeling and in vivo chemogenetic manipulations in mice, we first show that a time series metric estimated from fMRI BOLD signal, the Hurst exponent (H) can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently.