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

Published version
Peer-reviewed

Type

Article

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Authors

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

Abstract

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.

Description

Keywords

MRC AIMS Consortium

Journal Title

eLife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

Publisher

eLife Sciences Publications Ltd
Sponsorship
Department of Health (via National Institute for Health Research (NIHR)) (156239)
Medical Research Council (MC_G0802534)