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.

Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women / Trakoshis, S.; Martinez-Canada, P.; Rocchi, F.; Canella, C.; You, W.; Chakrabarti, B.; Ruigrok, A. N. V.; Bullmore, E. T.; Suckling, J.; Markicevic, M.; Zerbi, V.; Baron-Cohen, S.; Gozzi, A.; Lai, M. -C.; Panzeri, S.; Lombardo, M. V.. - In: ELIFE. - ISSN 2050-084X. - 9:(2020), pp. 1-31. [10.7554/ELIFE.55684]

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

Rocchi F.;Canella C.;
2020-01-01

Abstract

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.
2020
Trakoshis, S.; Martinez-Canada, P.; Rocchi, F.; Canella, C.; You, W.; Chakrabarti, B.; Ruigrok, A. N. V.; Bullmore, E. T.; Suckling, J.; Markicevic, M.; Zerbi, V.; Baron-Cohen, S.; Gozzi, A.; Lai, M. -C.; Panzeri, S.; Lombardo, M. V.
Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women / Trakoshis, S.; Martinez-Canada, P.; Rocchi, F.; Canella, C.; You, W.; Chakrabarti, B.; Ruigrok, A. N. V.; Bullmore, E. T.; Suckling, J.; Markicevic, M.; Zerbi, V.; Baron-Cohen, S.; Gozzi, A.; Lai, M. -C.; Panzeri, S.; Lombardo, M. V.. - In: ELIFE. - ISSN 2050-084X. - 9:(2020), pp. 1-31. [10.7554/ELIFE.55684]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/286623
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