Distinct brain activation patterns linked to clinical symptoms during hand grasping in Parkinson's disease.

Abstract

Objective This study aimed to investigate the characteristics of brain functional activation during a hand grasping task in patients with Parkinson's Disease (PD) using functional near-infrared spectroscopy (fNIRS), and to further explore the clinical factors associated with the level of regional brain activation. Methods Fifty-nine PD patients were enrolled. Demographic data (age, sex, education level) and clinical characteristics (disease duration, Hoehn-Yahr stage, UPDRS-III score, side of onset, motor complications, cognitive function, activities of daily living, non-motor symptoms, and levodopa equivalent daily dose) were collected for all participants. Oxygenated hemoglobin (HbO2) signals from multiple brain regions were acquired using fNIRS during a hand grasping task. With sex, age, and disease duration as covariates, multiple linear regression analysis was used to examine the relationships between clinical variables-including side of onset, constipation, REM sleep behavior disorder (RBD), Freezing of Gait (FOG), UPDRS-III, Montreal Cognitive Assessment (MoCA), and Hoehn-Yahr stage-and brain activation metrics (both temporal-domain and advanced features). Results Among the 59 PD patients, 38 (64.4%) had constipation and 17 (28.8%) had freezing of gait (FOG). Under the left-hand task, constipation was significantly positively correlated with parameters in 13 brain regions (pFDR < 0.05), mainly including the bilateral dorsolateral prefrontal cortex, left frontal eye field, and left premotor area (regression coefficients: 0.0033-0.8538). No other clinical variables showed significant associations. Under the right-hand task, FOG was significantly negatively correlated with the full width at half maximum (FWHM) of the right primary motor cortex (β = -8.52, 95% CI: -12.98 to -4.06, pFDR = 0.010). No other clinical variables showed significant associations; however, larger studies are needed to confirm these findings and to evaluate potential subtle effects, particularly for RBD. Conclusion In PD patients, constipation is associated with cortical hyperactivation in the prefrontal-premotor areas during the non-dominant hand task. Conversely, FOG correlates with reduced hemodynamic persistence and shortened activation duration in the right primary motor cortex (M1) during the dominant hand task. fNIRS can act as an objective tool to explore the cortical mechanisms of motor and non-motor symptoms in PD, providing hypothesis-generating evidence for potential targets that warrant further investigation in future repetitive transcranial magnetic stimulation (rTMS) intervention trials.