Understanding Parkinson’s disease and deep brain stimulation: Role of monkey models

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder affecting over 10 million people worldwide. In the 1930s and 1940s there was little understanding regarding what caused PD or how to treat it. In a desperate attempt to improve patients’ lives different regions of the neuraxis were ablated. Morbidity and mortality were common, but some patients’ motor signs improved with lesions involving the basal ganglia or thalamus. With the discovery of l-dopa the advent of medical therapy began and surgical approaches became less frequent. It soon became apparent, however, that medical therapy was associated with side effects in the form of drug-induced dyskinesia and motor fluctuations and surgical therapies reemerged. Fortunately, during this time studies in monkeys had begun to lay the groundwork to understand the functional organization of the basal ganglia, and with the discovery of the neurotoxin MPTP a monkey model of PD had been developed. Using this model scientists were characterizing the physiological changes that occurred in the basal ganglia in PD and models of basal ganglia function and dysfunction were proposed. This work provided the rationale for the return of pallidotomy, and subsequently deep brain stimulation procedures. In this paper we describe the evolution of these monkey studies, how they provided a greater understanding of the pathophysiology underlying the development of PD and provided the rationale for surgical procedures, the search to understand mechanisms of DBS, and how these studies have been instrumental in understanding PD and advancing the development of surgical therapies for its treatment.