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., Ruigrok AN., Bullmore ET., Suckling J., Markicevic M., Zerbi V., MRC AIMS Consortium None., Bailey AJ., Baron-Cohen S., Bolton PF., Bullmore ET., Carrington S., Catani M., Chakrabarti B., Craig MC., Daly EM., Deoni SC., Ecker C., Happé F., Henty J., Jezzard P., Johnston P., Jones DK., Lai M-C., Lombardo MV., Madden A., Mullins D., Murphy CM., Murphy DG., Pasco G., Ruigrok AN., Sadek SA., Spain D., Stewart R., Suckling J., Wheelwright SJ., Williams SC., Baron-Cohen S., Gozzi A., Lai M-C., Panzeri S., Lombardo MV.
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.