Interfacing basal ganglia models and Parkinson’s disease phenomenology: How can we translate the findings of electrophysiological studies from research to clinic

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. There are several models both of basal ganglia (BG) function and their dysfunction in PD. Degeneration of the nigrostriatal dopaminergic pathway is the key pathological feature of PD, leading to classical motor symptoms, such as bradykinesia and rigidity. A dysfunction of structures other than BG, including cerebellum and brainstem, may be involved in the generation of tremor and axial symptoms, while the degeneration of non-dopaminergic neurotransmitter systems is a likely contributing factor of non-motor symptoms. BG models provide hypotheses testable by electrophysiological research in humans. In PD patients with implanted deep brain stimulators, activity from BG nuclei, i.e. the subthalamic nucleus the internal pallidal segment, and from the peduncolopontine nucleus may be directly recorded using depth electrodes. Non-invasive electrophysiological techniques allow the investigation of dysfunctional BG through interconnections with motor cortical areas, brainstem and spinal structures. Electrophysiological studies have revealed functional abnormalities at every level of the central nervous systems, including BG nuclei, motor cortex, cerebellum, brainstem and spinal cord. Despite the progress in electrophysiological characterization of PD, with particular advances in understanding the role of pathological BG oscillatory activity in generating bradykinesia, there is still a large gap in understanding the pathophysiological relevance of other electrophysiological findings in PD. Better insight into the relationship between electrophysiological abnormalities and motor and non-motor symptoms in PD is likely to have important clinical implications.