Subcortical white matter hyperintensities and motor function in parkinson's disease: findings from the ONDRI study

Motor signs, such as rigidity, bradykinesia, tremor, gait and balance impairment, are hallmark features of idiopathic Parkinson's disease (PD). The basal ganglia, involved in voluntary and automatic movements, are affected by reduced dopaminergic activity, contributing to motor signs in PD. Motor signs may be exacerbated by cortical white matter hyperintensities (WMH), but the relationship between basal ganglia WMH and motor signs remains unclear.

To investigate the association between subcortical WMH burden and motor severity in PD participants.

This cross-sectional study included 140 PD participants from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). The relative WMH (i.e, percentage) in the whole brain, frontal, temporal, parietal, occipital lobes, and basal ganglia+thalamus (BGT) were calculated. Adjusted regression models were used to test the associations between WMH and motor signs. WMH burden was stratified by quartiles, and Analysis of Covariance was applied to determine which WMH quartile most affected motor signs.

Increased WMH burden in BGT was associated with better motor function. In contrast, WMH burden in cortical brain regions, i.e., frontal, parietal, temporal, and occipital lobes, was not associated with worse motor signs. Participants with larger BGT WMH volumes exhibited better motor function compared to those in lower quartiles CONCLUSION: Hyperintense lesions in the basal ganglia+thalamus were significantly associated with better motor function, suggesting that disruption of inhibitory basal ganglia circuitry may recalibrate motor output. These findings raise novel hypotheses about circuit-level modulation in Parkinson's disease and may guide future mechanistic and therapeutic investigations. However, as the results are correlational, they do not imply causality.