Distinct brain susceptibility alteration pattern in Parkinson's disease with drooling: evidence from quantitative susceptibility mapping.

BACKGROUND: Drooling is a common non-motor symptom in Parkinson's disease (PD) and can substantially impair quality of life, but its underlying neural mechanisms remain incompletely understood. Quantitative susceptibility mapping (QSM) provides a non-invasive approach for assessing susceptibility alterations related to brain iron deposition. This cross-sectional study aimed to investigate QSM-derived susceptibility alterations in PD patients with drooling (PD-DR) and to explore their associations with drooling severity. METHODS: A total of 103 participants, including 38 PD-DR, 23 PD patients without drooling (PD-NDR), and 42 healthy controls (HC), underwent three-dimensional (3D) magnetic resonance imaging including regular sequences and QSM. Voxel-wise whole-brain analysis and region of interest (ROI)-based analysis focusing on subcortical nuclei were performed to compare magnetic susceptibility values among groups, with voxel-wise significance set at voxel-level P<0.001 and cluster-level family-wise error-corrected P<0.05. Partial correlation analyses were performed in the PD-DR group to examine associations between susceptibility alterations in identified regions and drooling severity, after adjusting for age, sex, disease stage, and motor severity. RESULTS: Voxel-wise analysis revealed significantly increased susceptibility in the left superior temporal gyrus (STG) in the PD-DR group compared to the PD-NDR group (voxel-level P<0.001, cluster-level family-wise error-corrected P<0.05). In the PD-DR group, susceptibility values in the left STG showed a significant positive correlation with SCS-PD scores after adjusting for age, sex, Hoehn-Yahr stage, and Unified Parkinson's Disease Rating Scale Part III score (r=0.361, P=0.036). Compared to the HC group, the PD-DR group exhibited more widespread cortical susceptibility alterations. ROI analysis indicated higher susceptibility values in the left ventral pallidum (VP) and left parabrachial pigmented nucleus (PBP) in the PD-DR group compared to that in the HC group (Bonferroni-corrected P=0.042 and P=0.043, respectively). Furthermore, susceptibility values in the left PBP were significantly positively correlated with SCS-PD scores (r=0.506, P=0.002). CONCLUSIONS: Drooling in PD is associated with a distinct pattern of brain susceptibility alterations, supporting the involvement of a distributed neural network. Key regions include the left STG and the left PBP, which may be related to sensory integration, interoception, motivation, and motor control.