Dichotomizing Motor and Non-motor Correlates of Cholinergic Network Denervation in Parkinson’s Disease using Correlational Tractography

Motivation: Cholinergic denervation underlying clinical manifestations in Parkinson’s disease (PD) is complicated. Goal(s): To clarify motor vs non-motor correlates of cholinergic denervation in PD and identify potential novel therapeutic targets. Approach: We evaluated for significant associations between projections of the nucleus basalis of Meynert and pedunculopontine nucleus and motor/non-motor scores using correlational tractography in a case-control PD cohort. Results: Intracellular and extracellular diffusivity demonstrated significant correlations with motor, cognitive and sleep assessment scores in patients. Significantly reduced intra- and extracellular diffusivity of the PPN-cholinergic-motor projection were seen. The cholinergic projections were dichotomized where the most correlated segments innervated ventral posterolateral thalamic nuclei. Impact: The motor and non-motor correlates of cholinergic denervation show potential as objective clinical markers to characterize the PD spectrum while mapping of the cholinergic projection with highest correlation could identify substructure areas as novel stimulation target.