Characterization of Hemodynamic Alteration in Parkinson's Disease and Effect on Resting-State Connectivity

Functional magnetic resonance imaging (fMRI) is a convolution of latent neural activity and the hemodynamic response function (HRF). According to prior studies, the neurodegenerative process in idiopathic Parkinson's Disease (PD) interacts significantly with neuromuscular abnormalities. Although these underlying neuromuscular changes might influence the temporal characteristics of HRF and fMRI signals, relatively few studies have explored this possibility. We hypothesized that such alterations would engender changes in estimated functional connectivity (FC) in fMRI space compared to latent neural space. To test these theories, we calculated voxel-level HRFs by deconvolving resting-state fMRI data from PD patients (n = 61) and healthy controls (HC) (n = 47). Significant group differences in HRF (P < 0.05, Gaussian random field-corrected) were observed in several regions previously associated with PD. Subsequently, we focused on putamen-seed-based FC differences between the PD and HC groups using fMRI and latent neural signals. The results suggested that neglecting HRF variability may cultivate false-positive and false-negative FC group differences. Furthermore, HRF was related to dopamine receptor type 2 (DRD2) gene expression (P < 0.001, t = -7.06, false discover rate-corrected). Taken together, these findings reveal HRF variation and its possible underlying molecular mechanism in PD, and suggest that deconvolution could reduce the impact of HRF variation on FC group differences.