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

Trakoshis, S., Martínez-Cañada, P., Rocchi, F., Canella, C., You, W., Chakrabarti, B. ORCID: https://orcid.org/0000-0002-6649-7895, Ruigrok, A. N., Bullmore, E. T., Suckling, J., Markicevic, M., Zerbi, V., MRC AIMS Consortium, Baron-Cohen, S., Gozzi, A., Meng-Chuan, L., Panzeri, S. and Lombardo, M. V. (2020) Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women. eLife, 9. ISSN 2050-084X doi: 10.7554/eLife.55684

Abstract/Summary

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.