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An important and influential model that is widely accepted as an explanation for the mechanism of visual hallucinations in Parkinson\u2019s 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\u2019s 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\u2014defined as the directed (causal) influence that one region exerts on another region\u2014from 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\u2019s disease visual hallucinators and 75 Parkinson\u2019s 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\u2019s disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac329","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T06:18:37Z","timestamp":1670998717000},"source":"Crossref","is-referenced-by-count":37,"title":["Changes in both top-down and bottom-up effective connectivity drive visual hallucinations in Parkinson\u2019s disease"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6107-0326","authenticated-orcid":false,"given":"George E C","family":"Thomas","sequence":"first","affiliation":[{"name":"Dementia Research Centre, UCL Institute of Neurology , WC1N 3AR London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Zeidman","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology , WC1N 3AR London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tajwar","family":"Sultana","sequence":"additional","affiliation":[{"name":"Department of Computer and Information Systems Engineering, NED University of Engineering & Technology , Karachi 75270 , Pakistan"},{"name":"Department of Biomedical Engineering, NED University of Engineering & Technology , Karachi 74800 , Pakistan"},{"name":"Neurocomputation Laboratory, NCAI Computer and Information Systems Department, NED University of Engineering and Technology , Karachi 75270 , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2808-072X","authenticated-orcid":false,"given":"Angeliki","family":"Zarkali","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Institute of Neurology , WC1N 3AR London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeel","family":"Razi","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology , WC1N 3AR London , UK"},{"name":"Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University , Clayton, VIC 3800 , Australia"},{"name":"CIFAR Azrieli Global Scholars Program, CIFAR , Toronto, ON M5G 1M1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5092-6325","authenticated-orcid":false,"given":"Rimona S","family":"Weil","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Institute of Neurology , WC1N 3AR London , UK"},{"name":"Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology , WC1N 3AR London , UK"},{"name":"Movement Disorders Consortium, UCL , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"issue":"4","key":"2023022702524951900_","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1093\/brain\/123.4.733","article-title":"Hallucinations in Parkinson\u2019s disease. 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