Resting-State Prefrontal Hemodynamic Alterations in Parkinson’s Disease with Comorbid Depression: A Cross-Sectional fNIRS Study

Objective: To compare resting-state prefrontal mean baseline-referenced oxygenated hemoglobin concentration change (ΔHbO2) signals among patients with Parkinson’s disease with depression (PD-D), patients with PD without depression (PD-nD), and healthy controls (HCs). Methods: This cross-sectional study included 120 patients with PD, comprising 60 patients with depression and 60 without depression, as well as 60 healthy controls matched for age, sex, and years of education. Resting-state prefrontal hemodynamic signals were acquired using functional near-infrared spectroscopy. The mean baseline-referenced ΔHbO2 signal was calculated for each channel. Results: After correction for multiple comparisons, the mean baseline-referenced ΔHbO2 signal in CH13 (S8–D8) was significantly lower in the PD-D group than in the PD-nD and HC groups. After adjustment for Hamilton Anxiety Rating Scale (HAMA) and Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) scores and Hoehn–Yahr stage, S8–D8 channel mean baseline-referenced ΔHbO2 signal remained associated with comorbid depression. Each 0.01 μM increase in the mean baseline-referenced CH13 ΔHbO2 signal was associated with lower odds of comorbid depression (OR, 0.570; 95% CI, 0.434–0.747). In an exploratory internal validation analysis that repeated channel screening within 5000 bootstrap resamples, the optimism-corrected AUC was 0.779. Conclusions: The processed ΔHbO2 signal in CH13 differed between the PD-D and PD-nD groups and remained associated with depression-group status after adjustment for measured clinical covariates. This exploratory channel-level finding requires confirmation in independent cohorts.