Objective: The aim of this research was to investigate the basal ganglia (BG)-related functional gradient alterations and the association between these brain dysfunctions and clinical manifestations in Parkinson’s disease (PD).

Background: PD is the second most common neurodegenerative disease among aging people. PD is characterized by the progressive loss of dopaminergic neurons in the substantia nigra and dysfunction of BG circuits. Previous studies mainly focused on dysfunctional BG-related whole-brain networks. In contrast, the underlying streamlining pattern within the BG remains unclear.

Method: 102 PD patients and 88 age- and sex-match healthy controls (HCs) were enrolled in this research. We utilized functional gradient to reveal the BG-related brain functional hierarchies alterations based on the voxel-based functional connectivity using resting-state functional MRI data. The partial least squares correlation analysis was used to measure the correlations between brain gradient alterations and clinical features with age, sex, and levodopa-equivalent daily dosage as covariates.

Results: The results revealed two mainly functional gradient patterns. The first principal functional gradient was organized along a gradual axis from the caudate nucleus to the putamen (explained ratio: PD, 12.4 ± 5.1%; HCs, 14.4 ± 4.6%), while the second gradient was organized along a gradual axis within the caudate nucleus (explained ratio: PD, 9.4 ± 3.6%; HCs, 8.5 ± 2.8%). The between-group comparison indicated that the PD group had less variance, a narrower range of gradient scores, and less spatial variation than HCs in the principal gradient (all p < 0.05; age and sex as covariates). Additionally, the left nucleus accumbens and putamen showed higher gradient scores, while the right putamen showed lower gradient scores of the second gradient in PD patients than that in HCs (FDR correction). These dysfunctional gradient metrics were associated with motor symptoms and mood impairments.

Conclusion: This research for the first time unveiled the BG-related functional gradient in PD. The results provided a functional reorganization of the BG nuclei in PD. Moreover, functional segregation reduction was associated with motor deficits and mood impairment. These findings advance our understanding of the brain functional reorganization in PD.

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/abnormal-basal-ganglia-related-functional-gradient-in-parkinsons-disease/