Brain Connectivity Abnormalities Predating the Onset of Psychosis: Correlation With the Effect of Medication
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IMPORTANCE: Brain imaging studies have identified robust changes in brain structure and function during the development of psychosis, but the contribution of abnormal brain connectivity to the onset of psychosis is unclear. Furthermore, antipsychotic treatment can modulate brain activity and functional connectivity during cognitive tasks. OBJECTIVES: To investigate whether dysfunctional brain connectivity during working memory (WM) predates the onset of psychosis and whether connectivity parameters are related to antipsychotic treatment. DESIGN: Dynamic causal modeling study of functional magnetic resonance imaging data. SETTING: Participants were recruited from the specialized clinic for the early detection of psychosis at the Department of Psychiatry, University of Basel, Basel, Switzerland. PARTICIPANTS: Seventeen participants with an at-risk mental state (mean [SD] age, 25.24 [6.3] years), 21 individuals with first-episode psychosis (mean [SD] age, 28.57 [7.2] years), and 20 healthy controls (mean [SD] age, 26.5 [4] years). MAIN OUTCOME AND MEASURE: Functional magnetic resonance imaging data were recorded while participants performed an N-back WM task. Functional interactions among brain regions involved in WM, in particular between frontal and parietal brain regions, were characterized using dynamic causal modeling. Bayesian model selection was performed to evaluate the likelihood of alternative WM network architectures across groups, whereas bayesian model averaging was used to examine group differences in connection strengths. RESULTS: We observed a progressive reduction in WM-induced modulation of connectivity from the middle frontal gyrus to the superior parietal lobule in the right hemisphere in healthy controls, at-risk mental state participants, and first-episode psychosis patients. Notably, the abnormal modulation of connectivity in first-episode psychosis patients was normalized by treatment with antipsychotics. CONCLUSIONS AND RELEVANCE: Our findings suggest that the vulnerability to psychosis is associated with a progressive failure of functional integration of brain regions involved in WM processes, including visual encoding and rule updating, and that treatment with antipsychotics may have the potential to counteract this.
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DCM studies in schizophrenia demonstrated differences in functional network architecture and effective connectivity compared to healthy controls across various tasks.
“These studies demonstrated differences in functional network architecture and effective connectivity compared to healthy controls across various tasks.”
From Can Bayesian Theories of Autism Spectrum Disorder Help Improve Clinical Practice? (2016) · cites this paper as [132]
Validation studies in humans and animals show that DCM for EEG can capture short-term changes in synaptic efficacy, such as neuromodulation of glutamatergic receptor conductances, and distinguish different types of synaptic plasticity in cortical microcircuits.
“Validation studies in humans and animals have shown that DCM for EEG is capable of capturing short-term changes in synaptic efficacy, such as neuromodulation of glutamatergic receptor conductances, and distinguish different types of synaptic plasticity in cortical microcircuits (66, 132, 138–140)”
From Can Bayesian Theories of Autism Spectrum Disorder Help Improve Clinical Practice? (2016) · cites this paper as [132]
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- Authors
- Schmidt, A., Smieskova, R., Aston, J., Simon, A., Allen, P., Fusar-Poli, P., McGuire, P. K., Riecher-Rössler, A., Stephan, K. E., & Borgwardt, S.
- Affiliations
- University of Basel (CH)
- University of Bern (CH)
- King's College London (GB)
- National Health Service (GB)
- Wellcome Centre for Human Neuroimaging (GB)
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2013-09-01
- Volume
- 70
- Issue
- 9
- Pages
- 903
- ISSN
- 2168-622X (ISSN-L)
- OpenAlex
- W2127229574
- Cited by
- 93
- References
- 62
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 10 · 2018: 4 · 2017: 11 · 2016: 13 · 2015: 17 · 2014: 15 · 2013: 3
- FWCI
- 8.74
- Type
- journal article
- Language
- en
- Open access
- green
- edoc.unibas.ch
- Licence
- other-oa
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Wellcome Trust (091593)
- 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 and Behavioral Psychology Studies
- Keywords
- psychosis, clinical high risk for psychosis, first-episode psychosis, working memory, functional connectivity, dynamic causal modeling, antipsychotic drugs, frontoparietal network, middle frontal gyrus, superior parietal lobule, n-back task, rule updating, visual encoding, early detection of psychosis
- MeSH terms
- Adult, Brain, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Memory, Short-Term, Nerve Net, Neuropsychological Tests, Psychotic Disorders, Switzerland, Antipsychotic Agents, Young Adult
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