Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women Trakoshis, Stavros Martínez-Cañada, Pablo Rocchi, Federico Canella, Carola You, Wonsang Chakrabarti, Bhismadev Ruigrok, Amber NV Bullmore, Edward T Suckling, John Markicevic, Marija Zerbi, Valerio AIMS Consortium, MRC Baron-Cohen, Simon Gozzi, Alessandro Lai, Meng-Chuan Panzeri, Stefano Lombardo, Michael V 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. 2026-02-10T11:24:10Z 2026-02-10T11:24:10Z 2020-08-04 journal article Trakoshis, S.; Martínez-Cañada, P.; Rocchi, F. [et al.]. (2020). Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women. Trakoshis et al. eLife 2020; 9: e55684. DOI: https://doi.org/10.7554/eLife.55684 https://hdl.handle.net/10481/110817 10.7554/eLife.55684 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional eLife