ArticleBiological psychiatry2022
Computational Modeling of Electroencephalography and Functional Magnetic Resonance Imaging Paradigms Indicates a Consistent Loss of Pyramidal Cell Synaptic Gain in Schizophrenia.
Article in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.
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Who cites it
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 96 citations in OpenAlex.
- Discovery of biological markers for schizophrenia based on metabolomics: a systematic review.Frontiers in psychiatry · 2025Pooled it
- Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.Molecular psychiatry · 2023Pooled it
- A Dual Prediction Error Populations Model of Schizophrenia Spectrum Disorders: Bridging NMDA Hypofunction and Gain Hyperfunction.Schizophrenia bulletin · 2026Article
- Schizophrenia and disordered sensorimotor control: challenges, mechanisms and opportunities.Brain : a journal of neurology · 2026Review
- Restoring Synaptic Balance in Schizophrenia: Insights From a Thalamo-Cortical Conductance-Based Model.Schizophrenia bulletin · 2026Article
- Multimodal EEG-MRI Neuroimaging in Schizophrenia-A Systematic and Mechanistic Review.Journal of clinical medicine · 2026Review
- Bridging the Scales via Personalized Cellular Modeling and Deep Phenotyping in Schizophrenia.JAMA psychiatry · 2026Article
- Computational Modelling of Novelty Detection in the Mismatch Negativity Protocols and Its Impairments in Schizophrenia.The European journal of neuroscience · 2026Article
- The link between GABA levels and P300 abnormalities in schizophrenia spectrum disorders: regional and symptom-based insights.Schizophrenia (Heidelberg, Germany) · 2026Article
- Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis.Nature. Mental health · 2026Article
- Article
- Refining mechanistic models of hallucinations for enhanced translatability.Translational psychiatry · 2025Review
- Glutamate, Contextual Insensitivity, and Disorganized Speech in First-Episode Schizophrenia: A 7T Magnetic Resonance Spectroscopy Study.Biological psychiatry global open science · 2025Article
- A genetic algorithm for self-supervised models of oscillatory neurodynamics.bioRxiv : the preprint server for biology · 2025Article
- Excitation/inhibition imbalance and conversion to psychosis in the clinical high risk syndrome: Biophysical modeling finds reduced pyramidal cell excitability across EEG paradigms.medRxiv : the preprint server for health sciences · 2025Article
- Computational modeling of ketamine-induced changes in gamma-band oscillations: The contribution of parvalbumin and somatostatin interneurons.PLoS computational biology · 2025Article
- Neurophysiological Progression in Alzheimer's Disease: Insights From Dynamic Causal Modelling of Longitudinal Magnetoencephalography.Human brain mapping · 2025Article
- N-methyl-d-aspartate receptor hypofunction causes recurrent and transient failures of perceptual inference.Brain : a journal of neurology · 2025Article
- A computational account of joint SSRI and anti-inflammatory treatment.Frontiers in immunology · 2025Article
- Neuronal Synaptic Communication and Mitochondrial Energetics in Human Health and Disease.Advances in experimental medicine and biology · 2025Review
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundDiminished synaptic gain-the sensitivity of postsynaptic responses to neural inputs-may be a fundamental synaptic pathology in schizophrenia. Evidence for this is indirect, however. Furthermore, it is unclear whether pyramidal cells or interneurons (or both) are affected, or how these deficits relate to symptoms.
methodsPeople with schizophrenia diagnoses (PScz) (n = 108), their relatives (n = 57), and control subjects (n = 107) underwent 3 electroencephalography (EEG) paradigms-resting, mismatch negativity, and 40-Hz auditory steady-state response-and resting functional magnetic resonance imaging. Dynamic causal modeling was used to quantify synaptic connectivity in cortical microcircuits.
resultsClassic group differences in EEG features between PScz and control subjects were replicated, including increased theta and other spectral changes (resting EEG), reduced mismatch negativity, and reduced 40-Hz power. Across all 4 paradigms, characteristic PScz data features were all best explained by models with greater self-inhibition (decreased synaptic gain) in pyramidal cells. Furthermore, disinhibition in auditory areas predicted abnormal auditory perception (and positive symptoms) in PScz in 3 paradigms.
conclusionsFirst, characteristic EEG changes in PScz in 3 classic paradigms are all attributable to the same underlying parameter change: greater self-inhibition in pyramidal cells. Second, psychotic symptoms in PScz relate to disinhibition in neural circuits. These findings are more commensurate with the hypothesis that in PScz, a primary loss of synaptic gain on pyramidal cells is then compensated by interneuron downregulation (rather than the converse). They further suggest that psychotic symptoms relate to this secondary downregulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.