Mapping thalamocortical functional connectivity in chronic and early stages of psychotic disorders
Open accessAbstract
Background There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state functional magnetic resonance imaging has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis.Methods Resting-state functional magnetic resonance imaging was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early-stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions of interest (ROIs) on the basis of connectivity with six a priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxelwise seed-based analyses to further localize thalamic dysconnectivity.Results ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early-stage psychosis patients. PFC hypoconnectivity and motor cortex hyperconnectivity correlated in patients, suggesting that they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypoconnectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described executive control network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory.Conclusions Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment.
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Evidence supports the hypothesis that hallucinations arise from release of sensory signals by reduced top-down inhibition from higher-order centers such as frontal areas and their connections with the thalamus.
“In addition, evidence supports the hypothesis that hallucinations arise from release of those sensory signals by reduced top-down inhibition from higher-order centers such as frontal areas and their connections with the thalamus. 40-43”
From Towards an Integrative Account of Potential Mechanisms Mediating the Path From Sleep Dysfunction to Hallucinations (2025) · cites this paper as [43]
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- Authors
- Woodward, N. D., & Heckers, S.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Woodward, Neil D.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 79
- Issue
- 12
- Pages
- 1016-1025
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4698230
- OpenAlex
- W2202830236
- Cited by
- 264
- References
- 49
- Citations by year
- 2026: 13 · 2025: 26 · 2024: 33 · 2023: 25 · 2022: 26 · 2021: 30 · 2020: 29 · 2019: 38 · 2018: 18 · 2017: 16 · 2016: 9 · 2015: 1
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01-MH102266, Grant No. R01-MH070560)
- Vanderbilt Institute for Clinical and Translational Research (RR024975)
- 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 › Hallucinations in medical conditions
- Keywords
- thalamocortical connections, psychosis, chronic psychosis, prefrontal cortex, somatomotor cortex, frontoparietal network, cognitive impairment, verbal learning and memory, dorsolateral prefrontal cortex, medial prefrontal cortex, cerebellum
- MeSH terms
- Adult, Affective Disorders, Psychotic, Cerebellum, Cerebral Cortex, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Motor Cortex, Nerve Net, Psychotic Disorders, Schizophrenia, Thalamus, Prefrontal Cortex, Young Adult, Executive Function, Cognitive Dysfunction, Connectome
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