Regional Interplay for Temporal Processing in Parkinson's Disease: Possibilities and Challenges.

Michael Schwartze,Sonja A Kotz

doi:10.3389/fneur.2015.00270

Abstract

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.

Highlights

The basal ganglia system is a complex of several nuclei deeply embedded into the vertebrate brain
The cerebellum and the supplementary motor area (SMA) are affected in Parkinson’s disease (PD) and should be considered in a more encompassing view of the disease, their contribution to the overall pathogenesis is a matter of debate
Their contribution may be entirely secondary to the cell loss in the substantia nigra, which is the focus of basic research and therapeutic intervention

Summary

INTRODUCTION

The basal ganglia system is a complex of several nuclei deeply embedded into the vertebrate brain. Due to the fundamental nature of basal ganglia contributions to sequencing and interval timing, the conceptual and structural overlap between these functions has widespread implications, especially if the patterning and chunking of motor and cognitive action sequences and temporal processing in cortico-striatal circuits reflect aspects of an even more general sensorimotor sequencing capacity, which guides production and perception. Other studies have shown hypoactivation of the pre-SMA and the caudal portion of the SMA paralleled by hyperactivation of the ipsilateral cerebellum in patients performing repetitive paced button presses [34], as well as an augmented recruitment of cerebello-thalamo-cortical circuits in PD patients performing continued finger tapping following a pacing sequence with a base tempo of 500 ms [35] While these examples are clearly selective, they serve to illustrate that the experimental tasks applied in PD research vary widely. The heterogeneity of the results reflects this variability, highlighting the need for individualized approaches, potentially on the basis of individual temporal processing profiles

STRATEGIES FOR INTERVENTION

CONCLUSION