Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

Stavros Trakoshis,P. Martínez-Cañada,Federico Rocchi,Carola Canella,Wonsang You,B. Chakrabarti,A. Ruigrok,E. Bullmore,J. Suckling,M. Markicevic,V. Zerbi,S. Baron-Cohen,A. Gozzi,M. Lai,S. Panzeri,M. Lombardo

Published 2020 in bioRxiv

ABSTRACT

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.

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