Excitation-inhibition balance as a framework for investigating mechanisms in neuropsychiatric disorders
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In 2003 Rubenstein and Merzenich hypothesized that some forms of Autism (ASD) might be caused by a reduction in signal-to-noise in key neural circuits, which could be the result of changes in excitatory-inhibitory (E-I) balance. Here, we have clarified the concept of E-I balance, and updated the original hypothesis in light of the field's increasingly sophisticated understanding of neuronal circuits. We discuss how specific developmental mechanisms, which reduce inhibition, affect cortical and hippocampal functions. After describing how mutations of some ASD genes disrupt inhibition in mice, we close by suggesting that E-I balance represents an organizing framework for understanding findings related to pathophysiology and for identifying appropriate treatments.
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Neurophysiologically, researchers have noted an excitation/inhibition imbalance in ASD cortical circuits.
“Neurophysiologically, researchers have noted an excitation/inhibition imbalance in ASD cortical circuits (44, 45).”
From Predictive coding and neurocomputational psychiatry: a mechanistic framework for understanding mental disorders (2026) · cites this paper as [45]
The excitation versus inhibition balance is considered very important in the context of neuropsychiatric disease.
“The excitation versus inhibition balance is considered very important in the context of neuropsychiatric disease67.”
From Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses (2019) · cites this paper as [67]
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Three-dimensional synaptic Organization of Layer III of the human temporal neocortex
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3D synaptic organization of layer III of the human anterior cingulate and temporopolar cortex
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The sociability spectrum: evidence from reciprocal genetic copy number variations
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“Neurophysiologically, researchers have noted an excitation/ inhibition imbalance in ASD cortical circuits (44, 45).”
Modular arrangement of synaptic and intrinsic homeostatic plasticity within visual cortical circuits
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- Authors
- Sohal, V. S., & Rubenstein, J. L. R.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Sohal, Vikaas S.
- Rubenstein, John L. R.
- Venue
- Molecular Psychiatry
- Published
- 2019-05-14
- Volume
- 24
- Issue
- 9
- Pages
- 1248-1257
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC6742424
- OpenAlex
- W2945129130
- Cited by
- 988
- References
- 82
- Citations by year
- 2026: 153 · 2025: 213 · 2024: 158 · 2023: 123 · 2022: 120 · 2021: 142 · 2020: 68 · 2019: 9 · 2014: 1
- FWCI
- 11.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (MH081880, MH049428, MH100292, MH106507)
- Simons Foundation (309279)
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NS34661)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- excitation-inhibition balance, autism spectrum disorder, signal-to-noise ratio, neuronal inhibition, cortical function, hippocampal function, neural circuit development, neuropsychiatric disorders, pathophysiology, treatment goals
- MeSH terms
- Autism Spectrum Disorder, Animals, Mental Disorders, Brain, Disease Models, Animal, Hippocampus, Humans, Inhibition, Psychological, Nerve Net, Neurons, Mice
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