Fiber-specific white matter reductions in Parkinson hallucinations and visual dysfunction

Abstract

ObjectiveTo investigate the microstructural and macrostructural white matter changes that accompany visual hallucinations and low visual performance in Parkinson disease, a risk factor for Parkinson dementia.MethodsWe performed fixel-based analysis, a novel technique that provides metrics of specific fiber-bundle populations within a voxel (or fixel). Diffusion MRI data were acquired from patients with Parkinson disease (n = 105, of whom 34 were low visual performers and 19 were hallucinators) and age-matched controls (n = 35). We used whole-brain fixel-based analysis to compare microstructural differences in fiber density (FD), macrostructural differences in fiber bundle cross section (FC), and the combined FD and FC (FDC) metric 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.ResultsPatients with Parkinson 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. While there were no significant changes in FD, we found large reductions in the combined FDC metric in Parkinson hallucinators within the splenium (>50% reduction compared to nonhallucinators). Patients with Parkinson 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 left inferior fronto-occipital fasciculus.ConclusionsWe demonstrate specific white matter tract degeneration affecting posterior thalamic tracts in patients with Parkinson disease with hallucinations and low visual performance, providing direct mechanistic support for attentional models of visual hallucinations.

Visual dysfunction predicts cognitive impairment and white matter degeneration in Parkinson’s disease

“…PD low visual performers showed significant changes in white matter macro-and micro-structure compared to PD high visual performers, longitudinally ( Figure 3) and already at baseline ( Figure 4A), as we have shown previously 13 . At baseline, PD low visual performers showed reduction in FC within the splenium of the corpus callosum, the right cingulum and bilateral posterior thalamic radiation.…”

“…Performance in these tasks have been shown to correlate with cognitive but not lowlevel visual performance at baseline as well as worsening cognition at one-year follow up 5,17 . We have also shown that task performance is associated with fibre-specific white matter changes 13 .…”

“…14,24 Additionally, to investigate longitudinal change in selective fibre pathways within the visual system, we also performed tract of interest analyses. We selected 11 white matter tracts involved in visual processing, as in our previous work 13 : Posterior thalamic and optic radiations, Splenium, Body and Genu of the corpus callosum, Superior longitudinal fasciculi, Inferior fronto-occipital fasciculi (segmentation includes the inferior longitudinal fasciculus), and Superior fronto-occipital fasciculi.…”

“…We then calculated the mean FC across each tract per participant. FC was chosen for tract of interest analysis as prior works have shown it is the most sensitive fibre-specific metric of white matter degeneration in PD 13,14 . Mean FC at baseline and longitudinally was compared across PD low versus PD high visual performers.…”

“…We have previously described the white matter changes that are associated with low visual performance at baseline 13 . We found similar but significantly less extensive white matter changes in patients who later progressed to develop MCI, specifically involving the right hippocampus and the genu and splenium of the corpus callosum.…”