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Br J Radiol. 2019 Sep;92(1101):20180944. doi: 10.1259/bjr.20180944. Epub 2019 Jun 11.

Revisiting the excitation/inhibition imbalance hypothesis of ASD through a clinical lens.

Author information

1
1Department of Radiology, Lurie Family Foundations MEG Imaging Center, Children's Hospital of Philadelphia, Pennsylvania.
2
2Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
3
3Center for Neuroscience and Regenerative Medicine, Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland.

Abstract

Autism spectrum disorder (ASD) currently affects 1 in 59 children, although the aetiology of this disorder remains unknown. Faced with multiple seemingly disparate and noncontiguous neurobiological alterations, Rubenstein and Merzenich hypothesized that imbalances between excitatory and inhibitory neurosignaling (E/I imbalance) underlie ASD. Since this initial statement, there has been a major focus examining this exact topic spanning both clinical and preclinical realms. The purpose of this article is to review the clinical neuroimaging literature surrounding E/I imbalance as an aetiology of ASD. Evidence for E/I imbalance is presented from several complementary clinical techniques including magnetic resonance spectroscopy, magnetoencephalography and transcranial magnetic stimulation. Additionally, two GABAergic potential interventions for ASD, which explicitly attempt to remediate E/I imbalance, are reviewed. The current literature suggests E/I imbalance as a useful framework for discussing the neurobiological etiology of ASD in at least a subset of affected individuals. While not constituting a completely unifying aetiology, E/I imbalance may be relevant as one of several underlying neuropathophysiologies that differentially affect individuals with ASD. Such statements do not diminish the value of the E/I imbalance concept-instead they suggest a possible role for the characterization of E/I imbalance, as well as other underlying neuropathophysiologies, in the biologically-based subtyping of individuals with ASD for potential applications including clinical trial enrichment as well as treatment triage.

PMID:
31124710
PMCID:
PMC6732925
[Available on 2020-09-01]
DOI:
10.1259/bjr.20180944
[Indexed for MEDLINE]

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