eprintid: 10083549 rev_number: 44 eprint_status: archive userid: 608 dir: disk0/10/08/35/49 datestamp: 2019-10-18 17:26:09 lastmod: 2021-09-17 22:16:24 status_changed: 2020-06-09 10:36:15 type: article metadata_visibility: show creators_name: Weil, R creators_name: Zarkali, A creators_name: McColgan, P creators_name: Leyland, L creators_name: Lees, A creators_name: Rees, G title: Fibre-specific white matter reductions in Parkinson’s hallucinations and visual dysfunction ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F84 divisions: F86 divisions: C08 keywords: Parkinson’s disease, Parkinson’s disease dementia, diffusion weighted imaging, fixel, visual hallucinations, white matter note: Copyright © 2020 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. abstract: Objective: To investigate the microstructural and macrostructural white matter changes that accompany visual hallucinations and low visual performance in Parkinson’s disease, a risk factor for Parkinson’s dementia. Methods: We performed fixel-based analysis, a novel technique that provides metrics of specific fibre-bundle populations within a voxel (or fixel). Diffusion MRI data was acquired from patients with Parkinson’s disease (n=105, of which 34 low visual performers and 19 hallucinators) and age-matched controls (n=35). We used whole brain fixel-based analysis to compare micro-structural differences in fibre density (FD), macro-structural differences in fibre bundle cross-section (FC) and the combined fibre density and cross-section metric (FDC) across all white matter fixels. We then performed a tract of interest analysis comparing the most sensitive FDC metric across 11 tracts within the visual system. Results: Patients with Parkinson’s disease hallucinations exhibited macrostructural changes (reduced FC) within the splenium of the corpus callosum and the left posterior thalamic radiation compared to patients without hallucinations. Whilst there were no significant changes in FD, we found large reductions in the combined FDC metric in Parkinson’s hallucinators within the splenium (>50% reduction compared to non-hallucinators). Patients with Parkinson’s disease and low visual performance showed widespread microstructural and macrostructural changes within the genu and splenium of the corpus callosum, bilateral posterior thalamic radiations and the left inferior fronto-occipital fasciculus. Conclusions: We demonstrate specific white matter tract degeneration affecting posterior thalamic tracts in patients with Parkinson’s disease with hallucinations and low visual performance, providing direct mechanistic support for attentional models of visual hallucinations. date: 2020-04-07 date_type: published publisher: American Academy of Neurology official_url: https://doi.org/10.1212/WNL.0000000000009014 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1706004 doi: 10.1212/WNL.0000000000009014 lyricists_name: Lees, Andrew lyricists_name: Leyland, Louise-Ann lyricists_name: McColgan, Peter lyricists_name: Rees, Geraint lyricists_name: Weil, Rimona lyricists_name: Zarkali, Angeliki lyricists_id: AJLEE60 lyricists_id: LLEYL20 lyricists_id: PEMCC11 lyricists_id: GEREE91 lyricists_id: RSWEI70 lyricists_id: AZARK42 actors_name: Weil, Rimona actors_id: RSWEI70 actors_role: owner full_text_status: public publication: Neurology volume: 94 number: 14 pagerange: e1525-e1538 citation: Weil, R; Zarkali, A; McColgan, P; Leyland, L; Lees, A; Rees, G; (2020) Fibre-specific white matter reductions in Parkinson’s hallucinations and visual dysfunction. Neurology , 94 (14) e1525-e1538. 10.1212/WNL.0000000000009014 <https://doi.org/10.1212/WNL.0000000000009014>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10083549/1/Lees_WNL.0000000000009014.full.pdf