Get access

Milestones in research on the pathophysiology of Parkinson's disease§

Authors

  • Thomas Wichmann MD,

    Corresponding author
    1. Department of Neurology, School of Medicine, Emory University, Atlanta, Georgia, USA
    2. Yerkes National Primate Center at Emory University, Atlanta, Georgia, USA
    • Yerkes National Primate Center, Division of Neuropharmacology and Neurologic Diseases, 954 Gatewood Road, Atlanta, GA 30322, USA
    Search for more papers by this author
  • Mahlon R. DeLong MD,

    1. Department of Neurology, School of Medicine, Emory University, Atlanta, Georgia, USA
    Search for more papers by this author
  • Jorge Guridi MD,

    1. Department of Neurology, Clinica Universidad de Navarra and Medical School, Neuroscience Area, CIMA, University of Navarra, Pamplona, Spain
    2. Centros de Investigació Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Santander, Spain
    Search for more papers by this author
  • Jose A. Obeso MD

    1. Department of Neurology, Clinica Universidad de Navarra and Medical School, Neuroscience Area, CIMA, University of Navarra, Pamplona, Spain
    2. Centros de Investigació Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Santander, Spain
    Search for more papers by this author

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • 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).

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

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. © 2011 Movement Disorder Society

Ancillary