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

Neurology. 2020 Apr 7;94(14):e1525-e1538. doi: 10.1212/WNL.0000000000009014. Epub 2020 Feb 24.

Abstract

Objective: To 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.

Methods: We 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.

Results: Patients 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.

Conclusions: We 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / pathology
  • Corpus Callosum / diagnostic imaging
  • Corpus Callosum / pathology
  • Dementia / etiology
  • Diffusion Magnetic Resonance Imaging
  • Female
  • Hallucinations / etiology
  • Hallucinations / pathology*
  • Hallucinations / psychology*
  • Humans
  • Male
  • Middle Aged
  • Nerve Fibers / pathology*
  • Neuropsychological Tests
  • Parkinsonian Disorders / complications
  • Parkinsonian Disorders / pathology*
  • Parkinsonian Disorders / psychology*
  • Posterior Thalamic Nuclei / diagnostic imaging
  • Posterior Thalamic Nuclei / pathology
  • Pyramidal Tracts / diagnostic imaging
  • Pyramidal Tracts / pathology
  • Vision Disorders / etiology
  • Vision Disorders / pathology*
  • Vision Disorders / psychology*
  • White Matter / pathology*