Objective: To investigate the longitudinal progression of striatal dopaminergic dysfunction and its consequences on functional connectivity (FC) networks and clinical progression in Parkinson’s disease (PD) using a multimodal imaging approach.

Background: Multimodal imaging has proven useful in understanding the complex, interrelated disruptions in neurodegenerative diseases. PET has revealed striatal signaling deficits and an anterior-posterior gradient of dopaminergic dysfunction in PD has been put forward [1]. A growing body of literature suggests that the spatial distribution of affected striatal regions determines impaired cortical functional networks and thus the resulting clinical impairment.

Method: We evaluated the progression of striatal dopaminergic deficits, their functional connectivity to cortical areas, and their relationship to increasing disease severity in 17 clinically well-characterized PD-patients and 14 healthy controls (HC) undergoing ¹⁸F-DOPA-PET and resting-state functional MRI at two consecutive visits. Whole-brain group comparisons of PET Scans were performed as paired or two-sample-t-tests among patients’ baseline and follow-up visit scans or with respect to HCs’ scans. Resulting clusters were subjected to a seed-to-voxel FC analysis. Imaging findings and clinical scores were finally correlated via repeated-measures-ANOVA.

Results: Patients displayed a more pronounced dopaminergic impairment in the right caudate at the second visit compared to the first and in comparison to HCs. This hypodopaminergic caudate cluster exhibited lower FC to cortical sensorimotor areas compared to baseline. Reduced FC was more severe when FDOPA depletion was greater and correlated with motor progression. Furthermore, a greater decline in connectivity between visits was observed in anterior striatal regions.

Conclusion: Our study demonstrates progressive striatocortical degeneration and its impact on clinical disease progression in a combined PET and fMRI approach in well-defined PD-patients’ cohort. We found a progressive dopamine depletion more prone to anterior striatal structures and the consequent alterations on a network level. Both findings were associated with clinical worsening. Our findings highlight the usefulness of multimodal imaging approaches in understanding the connections between impaired dopaminergic transmission and functional connectivity on a network level.

References: Sawle, G. V., Playford, E. D., Burn, D. J., Cunningham, V. J. & Brooks, D. J. Separating Parkinson’s Disease from Normality: Discriminant Function Analysis of Fluorodopa F 18 Positron Emission Tomography Data. Arch. Neurol. 51, 237–243 (1994).

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/progression-of-striatocortical-dysfunction-in-parkinsons-disease-a-longitudinal-combined-pet-and-fmri-study/