Longitudinal thalamic white and grey matter changes associated with visual hallucinations in Parkinson’s disease
Open accessAbstract
Objective: Visual hallucinations are common in Parkinson’s disease (PD) and associated with worse outcomes. Large-scale network imbalance is seen in PD-associated hallucinations, but mechanisms remain unclear. As the thalamus is critical in controlling cortical networks, structural thalamic changes could underlie network dysfunction in PD hallucinations. Methods: We used whole-brain fixel-based analysis and cortical thickness measures to examine longitudinal white and grey matter changes in 76 patients with PD (15 hallucinators, 61 non-hallucinators) and 26 controls at baseline, and after 18 months. We compared white matter and cortical thickness, adjusting for age, gender, time-between-scans and intracranial volume. To assess thalamic changes, we extracted volumes for 50 thalamic subnuclei (25 each hemisphere) and mean fibre cross-section (FC) for white matter tracts originating in each subnucleus and examined longitudinal change in PD-hallucinators versus non-hallucinators. Results: PD hallucinators showed white matter changes within the corpus callosum at baseline and extensive posterior tract involvement over time. Less extensive cortical thickness changes were only seen after follow-up. White matter connections from the right medial mediodorsal magnocellular thalamic nucleus showed reduced FC in PD hallucinators at baseline followed by volume reductions longitudinally. After follow-up, almost all thalamic subnuclei showed tract losses in PD hallucinators compared with non-hallucinators. Interpretation: PD hallucinators show white matter loss particularly in posterior connections and in thalamic nuclei, over time with relatively preserved cortical thickness. The right medial mediodorsal thalamic nucleus shows both connectivity and volume loss in PD hallucinations. Our findings provide mechanistic insights into the drivers of network imbalance in PD hallucinations and potential therapeutic targets.
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Previous research has shown that the thalamus plays a role in VH in PD.
“Previous research has shown that the thalamus plays a role in VH in PD54,55”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [55]
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“Previous research has shown that the thalamus plays a role in VH in PD 54,55 , and a recent proposal 56 views the thalamus as a driver of unbalanced network recruitment, suggesting that it may induce decoupling between the default mode network and task-positive networks.”
- Authors
- Zarkali, A., McColgan, P., Leyland, L. A., Lees, A. J., & Weil, R. S.
- Affiliations
- University College London (GB)
- UCL Queen Square Institute of Neurology (GB)
- Wellcome Centre for Human Neuroimaging (GB)
- Corresponding author
- Zarkali, Angeliki
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2021-09-28
- Volume
- 93
- Issue
- 2
- Pages
- 169-179
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- PMC
- PMC8785065
- OpenAlex
- W3202766544
- Cited by
- 32
- References
- 62
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 1
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Alzheimer’s Research UK (2018B-001)
- Wellcome Clinical Research Career Development Fellowship (205167/Z/16/Z)
- National Institute for Health Research
- Wellcome (205167/Z/16/Z)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- Parkinson's disease, visual hallucinations, thalamus, white matter loss, gray matter changes, corpus callosum, cortical thickness, thalamic subnuclei, fixel-based analysis, fiber cross-section
- MeSH terms
- Aged, Corpus Callosum, Female, Hallucinations, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Parkinson Disease, Thalamus, White Matter, Gray Matter
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