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Post published on Twitter/X on 18 Jul 2022 12:07

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Javier Rasero, Antonio Jimenez-Marin, Ibai Diez, Roberto Toro, Mazahir T. Hasan, Jesus M. Cortes (2022). Autism excitation-inhibition imbalance linked to brain hyperconnectivity: An analysis based on 657 autistic subjects. openRxiv.

Publication date
16 Jul 2022
Identifier
10.1101/2022.07.14.500131
Authors
Javier Rasero, Antonio Jimenez-Marin, Ibai Diez, Roberto Toro, Mazahir T. Hasan, Jesus M. Cortes
Reference type
preprint
Publisher
openRxiv
Metadata source
crossref

Abstract

Abstract The large heterogeneity in autism spectrum disorder (ASD) is a major drawback for the development of therapies. Here, we apply consensus-subtyping strategies based on functional connectivity patterns to a population of N=657 quality-assured autistic subjects. We found two major subtypes (each divided hierarchically into several minor subtypes): Subtype 1 exhibited hypoconnectivity (less average connectivity than typically developing controls) and subtype 2, hyperconnectivity. The two subtypes did not differ in structural imaging metrics in any of the regions analyzed (64 cortical and 14 subcortical), nor in any of the behavioral scores (including Intelligence Quotient, ADI and ADOS). Finally, we used the Allen Human Brain Atlas of gene transcription to show that subtype 2, corresponding with about 42% of all patients, had significant enrichment (after multiple comparisons correction) to excitation-inhibition (E/I) imbalance, a leading reported mechanism in the developmental pathophysiology of ASD. Altogether, our results support a link between E/I imbalance and brain hyperconnectivity in ASD, an association that does not exist in hypoconnected autistic subjects.

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