Milestones in Research on the Pathophysiology of Parkinson's Disease

• Authors: Thomas Wichmann, Emory University; Mahlon R DeLong, Emory University; Jorge Guridi, University of Navarra; Jose A. Obeso, University of Navarra
• Journal Title: Movement Disorders
• Volume: Volume 26, Number 6
• Publisher: Wiley | 2011-05-01, Pages 1032-1041
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/mds.23695
• Subjects: Biology, Neuroscience; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Clinical Neurology; Neurosciences & Neurology; basal ganglia; direct pathway; indirect pathway; dyskinesias; deep brain stimulation; pallidotomy; MEDIUM SPINY NEURONS; PRIMATE SUBTHALAMIC NUCLEUS; GLOBUS-PALLIDUS NEURONS; DEEP BRAIN-STIMULATION; EXCITOTOXIC ACID LESIONS; BRAAK STAGING SCHEME; MPTP-TREATED MONKEYS; PRIMARY MOTOR CORTEX; HUMAN BASAL GANGLIA; POSTEROVENTRAL PALLIDOTOMY

Abstract

Progress in our understanding of the mechanisms underlying the cardinal motor abnormalities of Parkinson's disease (PD), in particular akinesia and bradykinesia and their treatment, has been remarkable. Notable accomplishments include insights into the functional organization of the basal ganglia and their place in the motor system as components of a family of parallel cortico-subcortical circuits that subserve motor and nonmotor functions and the development of models of the intrinsic organization of the basal ganglia, including delineation of the so-called direct, indirect, and hyperdirect pathways. Studies in primate models of PD have provided insight into the alterations of neuronal activity that are responsible for the motor features of PD, revealing both altered tonic levels of discharge and significant disturbances of the patterns of discharge throughout the motor circuitry and have led to the formulation of circuit models of PD, providing testable hypotheses for research and stimulating the development of new therapies. Most importantly, the discovery that lesions of the subthalamic nucleus, a key node of the indirect pathway, abolish the cardinal features of PD contributed to the renaissance in the use of surgical approaches to treating patients with PD, including ablation and deep brain stimulation.