Grey Matter Volume Differences Across Parkinson's Disease Motor Subtypes in the Supplementary Motor Cortex

Parkinson's Disease (PD) is the second most prevalent neurodegenerative disease worldwide due to loss of dopaminergic neurons projecting from the basal ganglia (BG). It is associated with various motor symptoms that are grouped into subtypes, each with different clinical presentations and disease progressions. Neuroimaging biomarkers focusing on regions a part of motor circuits projecting from the BG can distinguish and improve overall subtyping. The supplementary motor cortex (SMC) is well established in PD neuropathology and associated with freezing of gait and bradykinesia, but has not been thoroughly evaluated across subtypes. This study aims to identify volumetric differences of the SMC based on PD subtypes of tremor dominant (TD), postural instability with gait difficulty (PIGD), and akinetic rigid (AR) using data from Parkinson's Progression Markers Initiative. To segment grey matter volume and extract region of interest values, voxel-based processing was used. Multi-factor ANCOVAs, Tukey Honest Significance Test, and Kruskal-Wallis were utilized for volumetric analyses (α < 0.05). Subjects were classified and evaluated using TD, PIGD, and AR subtypes from the MDS-UPDRS rating scales. Inter-subtype differences in SMC GMV between TD and PIGD were significant in the right hemisphere for females (p = 0.01). No significant inter-subtype differences were found in the TD/AR system. These results support the use of broader motor networks, specifically the SMC in further understanding the neuropathological heterogeneity of PD. Furthermore, it reveals SMC differences across sexes, subtypes, and subtyping systems, calling for further evaluation of subtyping schemas, specifically regarding sex differences.