Distinct role of striatal functional connectivity and dopaminergic loss in Parkinson's symptoms

Degeneration of dopaminergic neurons is a hallmark of Parkinson's disease. However, its link to Parkinson's disease symptoms remains unclear. Striatal resting state functional connectivity differentiates between Parkinson's disease patients and healthy controls and might be a potential mediator of the effects of striatal dopaminergic degeneration onto Parkinson's disease symptoms. Here, we evaluated the relationship between dopaminergic deficits, striatal functional connectivity (SFC) at rest and different Parkinson's disease clinical symptoms in the largest currently established cohort of de novo Parkinson's disease patients. We show that SFC is an independent predictor of symptom severity in Parkinson's disease in addition to striatal dopaminergic deficits. Furthermore, we find that distinct SFC networks are associated with symptoms reflecting the ability to perform daily routine automatized motor tasks and clinician-rated Parkinson's disease motor symptoms. We find that reduced SFC is a major and independent predictor of Parkinson's disease symptoms going beyond the mere reflection of striatal dopaminergic input loss. These findings indicate the high value of SFC as a clinically relevant biomarker in Parkinson's disease.