Longitudinal functional connectivity changes related to dopaminergic decline in Parkinson’s disease

BACKGROUND: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated that basal ganglia functional connectivity is altered in Parkinson's disease (PD) as compared to healthy controls. However, such functional connectivity alterations have not been related to the dopaminergic deficits that occurs in PD over time. OBJECTIVES: To examine whether functional connectivity impairments are correlated with dopaminergic deficits across basal ganglia subdivisions in patients with PD both cross-sectionally and longitudinally. METHODS: ) was calculated for each participant. PD patients were assessed for disease severity. RESULTS: C-PE2I PET, showed larger decreases in posterior putamen functional connectivity with the midbrain and pallidum. Reduced functional connectivity of the posterior putamen with the thalamus, midbrain, supplementary motor area and sensorimotor cortex over time were significantly associated with changes in DAT density over the same period. Furthermore, increased motor disability was associated with lower intraregional functional connectivity of the posterior putamen. CONCLUSIONS: Our findings suggest that basal ganglia functional connectivity is related to integrity of dopaminergic system in patients with PD. Application of resting-state fMRI in a large cohort and longitudinal scanning may be a powerful tool for assessing underlying PD pathology and its progression.

Authors

• Weihua Li
• Nick P. Lao-Kaim
• Andreas-Antonios Roussakis
• Antonio Martín-Bastida
• Natalie Valle-Guzman
• Gesine Paul
• Eyal Soreq
• Richard E. Daws
• Tom Foltynie
• Roger A. Barker
• Adam Hampshire
• Paola Piccini

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