Regional interplay for temporal processing in Parkinson's disease: possibilities and challenges

Parkinson's disease (PD) is primarily associated with two dominant features: cardinal motor symptoms and the loss of cells in the substantia nigra pars compacta of the basal ganglia. Consequently, these aspects are major foci in PD-related research. However, PD is a neurodegenerative disease, which progressively affects multiple brain regions outside the basal ganglia and leads to symptoms outside the motor domain. Much less is known about the individual contribution of these secondary regions, their interplay and interaction with the basal ganglia, and the respective network dynamics in the overall manifestation of PD. These regions include classical motor structures such as the cerebellum and the supplementary motor area (SMA). However, just as the basal ganglia, these regions display a fine-grained microarchitecture, which supports sensory and sensorimotor functions. One such function is temporal processing, which has been ascribed to a network comprising all of these regions. On the one hand, pathological changes in this temporal processing network may be part and parcel of motor and non-motor symptoms in PD. On the other hand, a better understanding of the role of each network node may offer a novel perspective on compensatory mechanisms, therapeutic interventions, as well as the heterogeneity and individual differences associated with PD. We unfold this perspective by relating the neural foundations and functional implications of temporal processing to pathophysiological and neurofunctional changes characteristic of PD.