The pathophysiology of Parkinson's disease tremor

Tremor is one of the primary motor symptoms of Parkinson's disease (PD), and it is characterized by a highly phenomenological heterogeneity. Clinical and experimental observations suggest that tremor in PD cannot be interpreted merely as an expression of dopaminergic denervation of the basal ganglia. Accordingly, other neurotransmitter systems and brain areas are involved. We here review neurochemical, neurophysiological, and neuroimaging data as the basis of the presence of a dysfunctional network underlying tremor in PD. We will discuss the role of altered oscillations and synchronization in two partially overlapping central motor circuitries, e.g., the cerebello-thalamo-cortical and the basal ganglia-cortical loops. We will also emphasize the pathophysiological consequences of the abnormal interplay between the two systems. While there are many currently unknown and controversial aspects in the field, we will highlight the possible translational and practical implications of research advances in understanding tremor pathophysiology in PD. A better understanding of this issue is likely facilitating future therapeutic approaches to PD patients based on medications and invasive and non-invasive stimulation techniques. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.