Milestones in Research on the Pathophysiology of Parkinson's Disease

• Type of Material: Article
• Authors: Thomas Wichmann, Emory University; Mahlon R DeLong, Emory University; Jorge Guridi, University of Navarra; Jose A. Obeso, University of Navarra
• Language: English
• Date: 2011-05-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Movement Disorder Society.
• Final Published Version (URL): http://dx.doi.org/10.1002/mds.23695
• Title of Journal or Parent Work: Movement Disorders
• ISSN: 0885-3185
• Volume: 26
• Issue: 6
• Start Page: 1032
• End Page: 1041
• Grant/Funding Information: Writing this article was supported in part by NIH/NINDS grants R01NS054976 and P50NS071669 (to T.W.); and an infrastructure grant to the Yerkes National Primate Research Center (NIH/NCRR grant RR-000165).
• Keywords: PRIMATE SUBTHALAMIC NUCLEUS; Neurosciences & Neurology; MEDIUM SPINY NEURONS; POSTEROVENTRAL PALLIDOTOMY; EXCITOTOXIC ACID LESIONS; pallidotomy; Science & Technology; BRAAK STAGING SCHEME; basal ganglia; HUMAN BASAL GANGLIA; indirect pathway; Life Sciences & Biomedicine; GLOBUS-PALLIDUS NEURONS; dyskinesias; direct pathway; Clinical Neurology; MPTP-TREATED MONKEYS; PRIMARY MOTOR CORTEX; deep brain stimulation; DEEP BRAIN-STIMULATION
• Research Categories: Biology, Neuroscience; Health Sciences, Medicine and Surgery

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.