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

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Trakoshis, Stavros 
Martínez-Cañada, Pablo 
Rocchi, Federico 
Canella, Carola 
You, Wonsang 

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.

Research Article, Human Biology and Medicine, Neuroscience, autism, heterogeneity, sex/gender, excitation, inhibition, fMRI, Human, Mouse
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eLife Sciences Publications, Ltd
H2020 European Research Council (755816)
Simons Foundation (602849)
Medical Research Council (400061)
H2020 European Research Council (802371)