Sex-divergent intrinsic brain function in Parkinson’s disease: elevated nigral fluctuations and premotor-visuospatial coupling in female patients

IntroductionCortical and subcortical alterations in brain intrinsic function have been widely reported in Parkinson’s disease (PD). However, sex differences in brain intrinsic function in PD are poorly understood. This study aimed to examine sex differences in spontaneous brain intrinsic function in PD and their associations with neuropsychological measurements.MethodsUsing Parkinson’s Progression Markers Initiative (PPMI) resting-state fMRI, we compared amplitude of low-frequency fluctuations (ALFF) between male and female PD patients in substantia nigra (SN), globus pallidus (GP) and whole-brain. Subgroup analysis was performed, matching demographics with equal sample sizes. ALFF correlations with behavior were assessed by sex.ResultsFemale PD patients demonstrated higher ALFF in the right SN compared to males in the primary analysis. This sex difference achieved statistical significance in the demographics-matched subgroup analysis. Bilateral premotor ALFF was significantly elevated in female patients relative to males, independent of brain structure. Furthermore, right premotor ALFF showed a preliminary positive trend associated with visuospatial function exclusively in female PD patients.ConclusionFemale PD patients exhibit distinct functional signatures, primarily involving elevated premotor fluctuations and a preliminary premotor-visuospatial association. Preliminary SN alterations were also noted. These findings highlight the necessity of sex-stratified neuroimaging and provide preliminary support for premotor ALFF as a potential sex-divergent functional signature associated with cognitive profiling in female patients with PD.