eLife (Aug 2020)

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

  • Stavros Trakoshis,
  • Pablo Martínez-Cañada,
  • Federico Rocchi,
  • Carola Canella,
  • Wonsang You,
  • Bhismadev Chakrabarti,
  • Amber NV Ruigrok,
  • Edward T Bullmore,
  • John Suckling,
  • Marija Markicevic,
  • Valerio Zerbi,
  • MRC AIMS Consortium,
  • Simon Baron-Cohen,
  • Alessandro Gozzi,
  • Meng-Chuan Lai,
  • Stefano Panzeri,
  • Michael V Lombardo

DOI
https://doi.org/10.7554/eLife.55684
Journal volume & issue
Vol. 9

Abstract

Read online

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.

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