Mapping symptom domains and laterality to substantia nigra subregions in early Parkinson’s disease using neuromelanin MRI

Neuromelanin-sensitive MRI (NM-MRI) visualizes the substantia nigra (SN) and aids the diagnosis of Parkinson’s disease (PD), but whether its subregions map onto specific symptoms is unclear. In 105 patients with early PD, the SN was parcellated into ventral (associative), medial (limbic) and dorsolateral (sensorimotor) subregions. Compared with 50 reference participants, volumes were reduced bilaterally in all subregions (all p < 0.001); within patients, the loss was greater on the more affected side in the ventral, dorsolateral and total SN and symmetric in the medial SN. Volumes were correlated with the OFF-state MDS-UPDRS Part III, the MMSE, the cardiovagal and adrenergic subscores of the Composite Autonomic Scoring Scale (CASS) and orthostatic hypotension (OH). When each SN side was matched to its contralateral-body score, dorsolateral volume was the strongest correlate of motor severity (all FDR q ≤ 0.012). For symptoms without a lateralized counterpart, the correlations were carried by the less affected side ( q < 0.05): dorsolateral volume with the axial subscore ( r = −0.287) and OH ( r = −0.289), and medial volume with the cardiovagal ( r = −0.355) and adrenergic ( r = −0.336) subscores. In early PD, subregional NM-MRI volumes show symptom-oriented, laterality-dependent associations, with the dorsolateral SN tracking lateralized motor severity and the less affected medial SN relating to cardiovascular autonomic dysfunction.