Regional microstructural damage and patterns of eye movement impairment: a DTI and video-oculography study in neurodegenerative parkinsonian syndromes.

Abstract

Characteristic alterations of eye movement control are a common feature of neurodegenerative parkinsonism, including Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). Regional microstructural alterations as assessed by diffusion tensor imaging (DTI) have been reported in PD, PSP, and MSA. Therefore, we investigated the specific association between eye movement disturbances and microstructural impairment in these diseases. Video-oculographic recordings of smooth pursuit and visually guided reactive saccades as well as fractional anisotropy (FA) maps computed from whole-brain DTI data were analyzed for 36 PD, 30 PSP, 18 MSA patients, and 23 matched healthy control subjects. In PSP, peak eye velocity was pathologically slowed compared to controls (p<0.001) and correlated significantly with microstructural impairment in the midbrain (p<0.001, corrected). Smooth pursuit eye movements were substantially disturbed in MSA mainly by characteristic 'catch-up' saccades resulting in significantly reduced pursuit gain (p<0.001, corrected), and the shape of saccadized pursuit in MSA was significantly correlated with FA reductions in the middle cerebral peduncle (p<0.001, FDR corrected). The prevalence of saccadic intrusions as a measure for inhibitory control was significantly increased in PD compared with controls (p<0.001), but was uncorrelated with FA in cortical and subcortical white matter. Eye movement disturbances in PSP and MSA-but not in PD-are associated with diagnosis-specific regional microstructural alterations in the white matter. The non-invasive quantified oculomotor function analysis can give clues to the underlying structural connectivity network pathology and underpins its role as a technical marker in PSP and MSA.