Trakoshis, S;
Martínez-Cañada, P;
Rocchi, F;
Canella, C;
You, W;
Chakrabarti, B;
Ruigrok, AN;
... Lombardo, MV; + view all
(2020)
Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women.
eLife
, 9
, Article e55684. 10.7554/eLife.55684.
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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.
| Type: | Article |
|---|---|
| Title: | Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.55684 |
| Publisher version: | http://dx.doi.org/10.7554/eLife.55684 |
| Language: | English |
| Additional information: | Copyright Trakoshis et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
| Keywords: | autism, excitation, fMRI, heterogeneity, human, human biology, inhibition, medicine, mouse, neuroscience, sex/gender |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10108723 |
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