MRI structural and functional axial asymmetry in the brain-first versus body-first subtypes of Parkinson’s disease

Parkinson's Disease (PD) with Rapid Eye Movement Sleep Behavior Disorder (RBD) occurred before (body-first) and after (brain-first) motor symptoms may exhibit different MRI features. We aimed to investigate the structural and functional MRI pattern differences between brain-first and body-first subtypes of PD. 23 body-first and 19 brain-first PD patients, along with 20 matched healthy controls (HC) were enrolled and underwent T1-weighted and resting-state functional magnetic resonance imaging (rs-fMRI) scans in NJ-dataset. We calculated and compared amplitude of low-frequency fluctuations (ALFF) and gray matter volume (GMV) across groups to identify differential brain regions, which were subsequently extracted in PPMI and OASIS3 datasets. These values were combined with clinical data for binary classification machine learning training (with PPMI including 22 body-first and 35 brain-first patients used for feature selection and OASIS3 including 5 body-first and 10 brain-first patients used for external validation) and correlated with clinical scales. The body-first group exhibited higher zALFF values in the parietal lobe and greater GMV in the frontal lobe, while showing lower zALFF and GMV values in the cerebellum and subcortical nuclei (caudate nucleus for zALFF; medulla, hippocampus, amygdala, and olfactory bulb for GMV) than brain-first group. We identified significant axial asymmetry in functional and structural MRI between brain-first and body-first Parkinson's subtypes, characterized by greater gray matter retention and higher spontaneous neural activity in neocortex in the body-first subtype. Furthermore, integrating MRI and clinical scales effectively distinguished between brain-first and body-first subtypes.