Alterations of Brain Structure-Functional Coupling in Patients with Parkinson’s Disease Revealed by Diffusion and Functional MRI

Abstract

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor impairments such as bradykinesia, rigidity, and tremor, as well as non-motor symptoms, including cognitive dysfunction, mood disturbances, and autonomic dysregulation. Although these deficits are typically attributed to dopaminergic degeneration in the basal ganglia, emerging evidence suggests that PD-related pathology extends beyond subcortical structures, affecting multiple cortical networks. The interplay between structural connectivity (SC) and functional connectivity (FC) is increasingly recognized as a critical determinant of network integrity, yet the extent and specificity of SC-FC coupling alterations in PD remain poorly understood. This study investigates regional differences in SC-FC coupling in PD patients to elucidate patterns of network disorganization and potential compensatory mechanisms.Methods: A cohort of 28 patients diagnosed with PD and 26 age-matched healthy controls (HCs) underwent multimodal 3T MRI scanning, including diffusion-weighted imaging (DWI) and resting-state functional MRI (rs-fMRI). SC matrices were derived from probabilistic tractography using fiber orientation distribution modeling, while FC matrices were computed using pairwise correlations of regional mean time series. Pearson’s and Spearman’s correlation coefficients were employed to quantify SC-FC coupling at whole-brain and regional levels. To enhance statistical robustness, connectivity density analysis was performed to identify the most affected regions, followed by False Discovery Rate (FDR) correction to mitigate the risk of false positives in multiple comparisons.Results: PD patients exhibited significant reductions in SC-FC coupling across key cortical and subcortical regions, with the most pronounced decoupling observed in the anterior cingulate gyrus, postcentral gyrus, caudate, and putamen. These regions play pivotal roles in motor planning, sensory feedback, and executive control, suggesting that SC-FC decoupling may contribute to both movement impairments and higher-order dysfunctions in PD. The temporal pole and inferior temporal gyrus also exhibited reduced SC-FC coupling, implicating a broader cognitive and associative network disruption. Conversely, the thalamus demonstrated increased SC-FC coupling, potentially reflecting a compensatory mechanism within the basal ganglia-thalamocortical circuit, aimed at preserving network communication despite structural degradation.Conclusion: This study provides novel evidence of region-specific SC-FC coupling disruptions in PD, reinforcing the hypothesis that neurodegeneration in PD involves widespread alterations beyond the dopaminergic system. The findings suggest that certain subcortical structures may adaptively reorganize to counteract cortical decoupling, a hypothesis that warrants further investigation through longitudinal studies. Future research should focus on the progressive evolution of SC-FC coupling alterations and their potential role as biomarkers for tracking disease progression or therapeutic response.