Functional hierarchy underlies preferential connectivity disturbances in schizophrenia
Open accessAbstract
Significance: Schizophrenia is linked to widespread neuronal-level changes causing cortical excitation-inhibition imbalance. However, functional neuroimaging reveals preferential association network dysconnectivity. Therefore, a tension exists between two competing frameworks: global versus localized neural dysfunction in schizophrenia. To link these levels of analysis, this study initially simulated cellular-level glutamatergic deficits, generating network-level predictions of cortical imbalance. Schizophrenia results revealed widespread hyperconnectivity in line with model predictions, yet effects were most profound within association networks. These clinical effects were computationally captured by considering a pre-existing functional cortical hierarchy between association and sensory regions. This study reveals that widespread cellular deficits in schizophrenia can give rise to network-preferential disruptions observed in neuroimaging as an emergent property of pre-existing functional differences between cortical areas.
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Disruption of corollary discharge as a form of predictive signaling may be more broadly relevant for both hallucinations and delusions, which both entail aberrant inferences about agency and the intentions of others.
“In this case, disruption of corollary discharge as a form of predictive signaling may be more broadly relevant for both hallucinations and delusions, which both entail aberrant inferences about agency and the intentions of others.”
From The Predictive Coding Account of Psychosis (2018) · cites this paper as [87]
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References 130 · Cited by 153
- Authors
- Yang, G. J., Murray, J. D., Wang, X.-J., Glahn, D. C., Pearlson, G. D., Repovs, G., Krystal, J. H., & Anticevic, A.
- Affiliations
- Yale University (US)
- New York University Shanghai (CN)
- Hartford Hospital (US)
- Department of Psychology, University of Ljubljana, 1000 Ljubljana, Slovenia;
- Corresponding author
- Anticevic, Alan
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-12-23
- Volume
- 113
- Issue
- 2
- Pages
- E219-28
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4720350
- OpenAlex
- W2203684141
- Cited by
- 153
- References
- 130
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 20 · 2023: 14 · 2022: 12 · 2021: 16 · 2020: 16 · 2019: 11 · 2018: 17 · 2017: 11 · 2016: 8
- FWCI
- 7.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Yale University
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (DP50D012109-02, MH43775, MH074797)
- National Institute on Alcohol Abuse and Alcoholism (P50AA012870)
- National Institute of Mental Health (MH‐077945, R01MH062349, R01MH043775, MH074797, R01MH080912, R01MH074797, MH080912, MH43775, R37MH043775, F30MH107149, R01MH077945)
- National Institute of General Medical Sciences (T32GM007205)
- National Institute of Neurological Disorders and Stroke (T32NS007224)
- National Center for Chronic Disease Prevention and Health Promotion (DP50D012109-02)
- Yale Center for Clinical Investigation, Yale School of Medicine
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- schizophrenia, excitatory-inhibitory imbalance, functional connectivity, hyperconnectivity, association cortex, frontoparietal network, bipolar disorder, neural microcircuits, network hierarchy, resting-state functional connectivity, symptom severity
- MeSH terms
- Brain, Computer Simulation, Frontal Lobe, Humans, Models, Neurological, Nerve Net, Neural Inhibition, Parietal Lobe, Schizophrenia
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