Parkinson's Disease and the Basal Ganglia: Lessons from the Laboratory and from Neurosurgery

Thomas Wichmann, Jerrold L. Vitek, Mahlon R. Delong

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

During the last decade, a clearer understanding of the circuitry of the basal ganglia and their mode of operation has emerged. The basal ganglia are now viewed as parts of larger, segregated circuits that involve the thalamus and cerebral cortex. A pathophysiological model has been elaborated and tested in which Parkinsonian signs are viewed as resulting from increased activity of neurons in the motor portion of the internal pallidum, the major output nucleus of the basal ganglia, leading to increased inhibition of thalamocortical projection neurons and decreased activation of the precentral motor fields. Increased internal pallidal activity is thought to result from striatal dopamine loss, leading to decreased inhibition of the internal pallidum via a monosynaptic (direct) striatopallidal pathway and to excessive excitatory glutamatergic drive via a polysynaptic (indirect) striatopallidal pathway. Because current medical therapies for Parkinson's disease, aimed at systemically replacing dopamine, often lose their effectiveness after several years, with patients suffering from motor fluctuations and drug-induced dyski nesias, several new therapeutic strategies have been developed. In addition to the transplantation of dopaminergic tissue, other strategies attempt to reduce increased basal ganglia outflow directly by the placement of stereotactic lesions into the sensorimotor portion of the internal pallidum (pallidotomy) or by the chronic electric stimulation of the subthalamic nucleus. Preliminary results suggest that these new techniques may lead to significant improvement in Parkinsonian signs, motor fluctuations, and drug- induced dyskinesias.

Original languageEnglish (US)
Pages (from-to)236-244
Number of pages9
JournalThe Neuroscientist
Volume1
Issue number4
DOIs
StatePublished - Jul 1995

Keywords

  • Basal ganglia
  • Globus pallidus
  • Pallidotomy
  • Parkinson's disease
  • Stereotactic surgery
  • Subthalamic nucleus

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