Signed Dopaminergic Asymmetry Tracks Contralateral Motor Laterality in Parkinsons Disease

Abstract

Parkinson's disease is asymmetric, but representations that collapse left--right measurements discard that direction. We separated overall dopamine-transporter availability from hemispheric distribution: mean putamen specific-binding ratio (SBR) indexed overall DaT signal, whereas signed asymmetry retained which hemisphere was relatively more affected. Signed asymmetry aligned with contralateral MDS-UPDRS Part III laterality in PPMI (n=1,367; r=0.676) and S4 (n=56; r=0.551). In 1,204 PPMI landmarks, each 0.1 asymmetry corresponded to a 0.0507 increase in 12-month laterality (95\% CI 0.0387--0.0626); held-out \(R^2\) improved 0.0176 over non-directional imaging but was uncertain under a bounded link. Exploratory imaging--clinical disagreement marked lower side persistence (OR=0.491 per IQR-standardized unit; 0.297--0.711). Signed direction therefore distinguishes mirror-image and conflicting dopaminergic--motor states erased by mean-only summaries. This is a reproducible biological coordinate, not global progression, treatment benefit or clinical utility.