Distinct Role of Striatal Functional Connectivity and Dopaminergic Loss in Parkinson's Symptoms.

Juergen Dukart,Fabio Sambataro,Alessandro Bertolino

doi:10.3389/fnagi.2017.00151

Abstract

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.

Highlights

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is associated with loss of dopaminergic projections from substantia nigra to the striatum
The Unified Parkinson’s Disease Rating Scale (UPDRS) II subscale was significantly correlated with striatal functional connectivity (SFC) II regions (r = −0.46, p < 0.001) and with SFC total (r = −0.47, p < 0.001), SFC III (r = −0.27, p = 0.021), with DAT striatal binding in ipsilateral putamen (r = −0.31, p = 0.009) and in bilateral caudate nucleus
We show that SFC provides an independent and comparably strong link to PD clinical symptoms as the striatal dopaminergic deficits

Summary

Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is associated with loss of dopaminergic projections from substantia nigra to the striatum This decline of dopamine signaling initiates a pathological cascade encompassing numerous brain regions (Lotharius and Brundin, 2002; Dauer and Przedborski, 2003). UPDRS part II covers self-evaluation of highly automatized motor aspects of daily living Retention of such automatized motor functions is closely associated with a striato-cerebellar circuitry (Doyon et al, 1998; Lang and Bastian, 2002). UPDRS part III provides a direct evaluation of current motor deficits by the clinician For this subscale, a stronger involvement of striatal, motor, premotor and prefrontal regions involved in execution and planning is expected (Goldberg, 1985; Doyon et al, 1998; Petrides, 2005). A common mechanism underlying all symptoms captured by UPDRS subscales appears unlikely

Objectives

Methods

Results

Conclusion