Changes in both top-down and bottom-up effective connectivity drive visual hallucinations in Parkinson’s disease
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Abstract
Visual hallucinations are common in Parkinson’s disease and are associated with a poorer quality of life and a higher risk of dementia. An important and influential model that is widely accepted as an explanation for the mechanism of visual hallucinations in Parkinson’s disease and other Lewy body diseases is that these arise due to aberrant hierarchical processing, with impaired bottom-up integration of sensory information and overweighting of top-down perceptual priors within the visual system. This hypothesis has been driven by behavioural data and supported indirectly by observations derived from regional activation and correlational measures using neuroimaging. However, until now, there was no evidence from neuroimaging for differences in causal influences between brain regions measured in patients with Parkinson’s hallucinations. This is in part because previous resting-state studies focused on functional connectivity, which is inherently undirected in nature and cannot test hypotheses about the directionality of connectivity. Spectral dynamic causal modelling is a Bayesian framework that allows the inference of effective connectivity—defined as the directed (causal) influence that one region exerts on another region—from resting-state functional MRI data. In the current study, we utilize spectral dynamic causal modelling to estimate effective connectivity within the resting-state visual network in our cohort of 15 Parkinson’s disease visual hallucinators and 75 Parkinson’s disease non-visual hallucinators. We find that visual hallucinators display decreased bottom-up effective connectivity from the lateral geniculate nucleus to primary visual cortex and increased top-down effective connectivity from the left prefrontal cortex to primary visual cortex and the medial thalamus, as compared with non-visual hallucinators. Importantly, we find that the pattern of effective connectivity is predictive of the presence of visual hallucinations and associated with their severity within the hallucinating group. This is the first study to provide evidence, using resting-state effective connectivity, to support a model of aberrant hierarchical predictive processing as the mechanism for visual hallucinations in Parkinson’s disease.
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A recent spectral DCM fMRI study found involvement of the LGN of the thalamus, together with ventral visual regions, in PD-VH.
“A recent spectral DCM fMRI study found an involvement of the LGN of the thalamus, together with ventral visual regions, in PD-VH8.”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [8]
The Methods (Within-subject analysis; page unavailable) confirm that the study used spectral DCM on fMRI data. The Results (Effect of visual hallucinations on visual network architecture; page unavailable) report altered LGN connectivity in Parkinson’s disease with visual hallucinations. But the study’s specified regions include primary visual cortex (V1), not regions identified as ventral visual regions, so that part of the claim is unsupported. (LLM, conf=0.87)
Experimental — accuracy not yet measuredA recent spectral DCM fMRI study found an involvement of the LGN of the thalamus, together with ventral visual regions, in PD-VH.
“A recent spectral DCM fMRI study found an involvement of the LGN of the thalamus, together with ventral visual regions, in PD-VH8.”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [8]
The Methods (Within-subject analysis; page unavailable) confirm that the study used spectral DCM of fMRI data, and the Results (Effect of visual hallucinations on visual network architecture; page unavailable) report LGN connectivity differences in Parkinson’s disease with visual hallucinations. The defined network included V1, hippocampus and PFC, but the paper does not identify or report a finding specifically about ventral visual regions. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMorphological and functional alterations differentiate patients with PD with VH from those without VH.
“Although morphological5–7 and functional7–9 alterations differentiate patients with PD with VH (PD-VH) from those without VH”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [8]
A spectral DCM study using resting-state fMRI found increased resting-state top-down and reduced bottom-up connectivity in the visual network in PD with VH, a pattern predictive of hallucination severity.
“a spectral DCM study (using resting-state functional magnetic resonance imaging (fMRI)) found increased resting-state top-down and reduced bottom-up connectivity in the visual network in PD with VH, a pattern that was predictive of hallucination severity8”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [8]
A recent DCM fMRI study found that the pattern of altered connectivity observed at rest was predictive of hallucinations severity in PD.
“A recent DCM fMRI study found that the pattern of altered connectivity observed at rest was predictive of hallucinations severity in PD8.”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [8]
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Multimodal MRI of the hippocampus in Parkinson’s disease with visual hallucinations
Yao, N., Cheung, C., Pang, S. Y.-Y., Chang, R. S., Lau, K. K., John Suckling, A., Yu, K., Mak, H. K., Chua, S. E., Ho, S., et al. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0907-5 · Cited by 62 · see citing works
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Self-citationLoss of Functional Connectivity in Patients with Parkinson Disease and Visual Hallucinations
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Walpola, I. C., Muller, A. J., Hall, J. M., Andrews‐Hanna, J. R., Irish, M., Lewis, S. J. G., Shine, J. M., & O’Callaghan, C. (2020) · Cortex · doi:10.1016/j.cortex.2019.12.023 · Cited by 41 · see citing works
Zarkali, A., McColgan, P., Leyland, L. A., Lees, A. J., & Weil, R. S. (2022) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2021-326630 · Cited by 32 · see citing works
Self-citationWhat can we learn from fMRI capture of visual hallucinations in Parkinson’s disease?
Dujardin, K., Roman, D., Baille, G., Pins, D., Lefebvre, S., Delmaire, C., Defebvre, L., & Jardri, R. (2019) · Brain Imaging and Behavior · doi:10.1007/s11682-019-00185-6 · Cited by 29 · see citing works
Hallucinations and conscious access to visual inputs in Parkinson’s disease
Lefebvre, S., Baille, G., Jardri, R., Plomhause, L., Szaffarczyk, S., Defebvre, L., Thomas, P., Delmaire, C., Pins, D., & Dujardin, K. (2016) · Scientific Reports · doi:10.1038/srep36284 · Cited by 27 · see citing works
Visual Dysfunction of the Superior Colliculus in De Novo Parkinsonian Patients
Moro, E., Bellot, E., Meoni, S., Pélissier, P., Hera, R., Dojat, M., Coizet, V., & on behalf of the Superior Colliculus Study Group (2020) · Annals of Neurology · doi:10.1002/ana.25696 · Cited by 22 · see citing works
Limbic thalamus atrophy is associated with visual hallucinations in Lewy body disorders
Matar, E., Brooks, D., Lewis, S. J. G., & Halliday, G. M. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.01.001 · Cited by 15 · see citing works
Effective connectivity in subcortical visual structures in de novo Patients with Parkinson’s Disease
Bellot, E., Kauffmann, L., Coizet, V., Meoni, S., Moro, E., & Dojat, M. (2021) · NeuroImage Clinical · doi:10.1016/j.nicl.2021.102906 · Cited by 12 · see citing works
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Early detection of dementia with default-mode network effective connectivity
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Dysregulated connectivity configuration of triple-network model in obsessive-compulsive disorder
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Structural and Functional Imaging Correlates of Visual Hallucinations in Parkinson’s Disease
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Self-citationStructural MRI study of Pareidolia and Visual Hallucinations in Drug–Naïve Parkinson’s disease
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Functional connectivity in Lewy body disease with visual hallucinations
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Visual Hallucinations in Serotonergic Psychedelics and Lewy Body Diseases
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“We also computed the same models with MoCA and then LEDD as covariates to accommodate the potential role of general cognition and medication (Supplementary Information 8).”
InfluentialShould we standardize PhD training in neuroscience?
Spires‐Jones, T. L. (2023) · Brain Communications · doi:10.1093/braincomms/fcad028
Brain Communications 2023 early career researcher paper prize
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Seo, K., Hara, M., Alaoui, S. H., & Oyama, G. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.2005253
- Authors
- Thomas, G. E. C., Zeidman, P., Sultana, T., Zarkali, A., Razi, A., & Weil, R. S.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- Wellcome Centre for Human Neuroimaging (GB)
- NED University of Engineering and Technology (PK)
- Canadian Institute for Advanced Research (CA)
- Corresponding author
- Thomas, George E C
- Venue
- Brain Communications
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-12-14
- Volume
- 5
- Issue
- 1
- Pages
- fcac329-fcac329
- ISSN
- 2632-1297 (ISSN-L)
- PMC
- PMC9798302
- OpenAlex
- W4311493680
- Cited by
- 38
- References
- 96
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 13 · 2023: 8 · 2022: 1
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Brain Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Medical Research Council (MR/N013867/1)
- Wellcome Centre for Human Neuroimaging (203147/Z/16/Z)
- Alzheimer’s Research UK Clinical Research Fellowship (2018B-001)
- Australian Research Council (DE170100128, DP200100757)
- Australian National Health and Medical Research Council Investigator Grant (1194910)
- Canadian Institute for Advanced Research Azrieli Global Scholar in the Brain, Mind & Consciousness Program
- Wellcome Clinical Research Career Development Fellowship (205167/Z/16/Z)
- Parkinson’s UK, the Cure Parkinson’s Trust
- University College London Hospitals Biomedical Research Centre (BRC302/NS/RW/101410)
- National Institute for Health Research
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- visual hallucinations, Parkinson's disease, effective connectivity, top-down connectivity, predictive processing, lateral geniculate nucleus, primary visual cortex, prefrontal cortex, thalamus, Lewy body disease
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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