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In eLife

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.

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, Bailey Anthony J, Baron-Cohen Simon, Bolton Patrick F, Bullmore Edward T, Carrington Sarah, Catani Marco, Chakrabarti Bhismadev, Craig Michael C, Daly Eileen M, Deoni Sean Cl, Ecker Christine, Happé Francesca, Henty Julian, Jezzard Peter, Johnston Patrick, Jones Derek K, Lai Meng-Chuan, Lombardo Michael V, Madden Anya, Mullins Diane, Murphy Clodagh M, Murphy Declan Gm, Pasco Greg, Ruigrok Amber Nv, Sadek Susan A, Spain Debbie, Stewart Rose, Suckling John, Wheelwright Sally J, Williams Steven C, Baron-Cohen Simon, Gozzi Alessandro, Lai Meng-Chuan, Panzeri Stefano, Lombardo Michael V


autism, excitation, fMRI, heterogeneity, human, human biology, inhibition, medicine, mouse, neuroscience, sex/gender