title: Pathophysiologic basis of surgery for Parkinson's disease.
abstract: Dopamine depletion induces a series of changes in the basal ganglia motor circuit that underlie the origin of the cardinal features of Parkinson's disease. It has now been established that hyperactivity of the subthalamic nucleus (STN) is an essential feature of the parkinsonian state. This leads to increased excitatory driving onto the globus pallidum internum (GPi) and substantia nigra reticulata (SNr) which, in turn, overinhibits the motor projections to the thalamus and brainstem. The STN and GPi have become the preferred targets for surgery to treat PD. In keeping with the classic pathophysiologic model, physiologic and neuroimaging studies in patients have shown that lesioning or functional blockades (by deep brain stimulation, or DBS) of these nuclei increased cortical activation, in parallel with clinical improvements of bradykinesia. Neuronal recording during surgery has also shown tremor-related activity in both the STN and GPi. However, the pathophysiologic model of the basal ganglia needs further refinement to provide a more detailed explanation of the origin of both tremor and rigidity in Parkinson's disease and to explain the antidyskinetic effect of surgery of the GPi and STN.
authors.affiliation: Department of Neurology and Neurosurgery, Clinica Universitaria and Medical School, University of Navarra, Pamplona, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Obeso
authors.forename: M C
authors.initials: MC
authors.lastname: Rodriguez-Oroz
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez
authors.forename: R
authors.initials: R
authors.lastname: Macias
authors.forename: L
authors.initials: L
authors.lastname: Alvarez
authors.forename: J
authors.initials: J
authors.lastname: Guridi
authors.forename: J
authors.initials: J
authors.lastname: Vitek
authors.forename: M R
authors.initials: MR
authors.lastname: DeLong
mesh_terms: D001479:Basal Ganglia / Q000503:physiopathology*; D006801:Humans; D010300:Parkinson Disease / Q000503:physiopathology* / Q000601:surgery*