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

By Stavros Trakoshis, Pablo Martínez-Cañada, Federico Rocchi, Carola Canella, Wonsang You, Bhismadev Chakrabarti, Amber N. V. Ruigrok, Edward T. Bullmore, John Suckling, M. Markicevic, Valerio Zerbi, MRC AIMS Consortium, Simon Baron-Cohen, Alessandro Gozzi, Meng-Chuan Lai, Stefano Panzeri, Michael V. Lombardo

Posted 27 Jan 2020
bioRxiv DOI: 10.1101/2020.01.16.909531 (published DOI: 10.7554/eLife.55684)

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. ### Competing Interest Statement E.T.B. is employed half-time by the University of Cambridge and half-time at GlaxoSmithKline plc (GSK); he holds stock in GSK. All other authors have no conflict of interests to declare.

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