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The basal ganglia in Parkinson's disease: Current concepts and unexplained observations
Author(s) -
Obeso Jose A.,
Marin Concepcio,
RodriguezOroz C.,
Blesa Javier,
BenitezTemiño B.,
MenaSegovia Juan,
Rodríguez Manuel,
Olanow C. Warren
Publication year - 2008
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21481
Subject(s) - globus pallidus , basal ganglia , subthalamic nucleus , neuroscience , substantia nigra , parkinson's disease , indirect pathway of movement , pars reticulata , psychology , direct pathway of movement , dopaminergic , deep brain stimulation , dopamine , central nervous system , disease , medicine , pathology
The pathophysiology of Parkinson's disease is reviewed in light of recent advances in the understanding of the functional organization of the basal ganglia (BG). Current emphasis is placed on the parallel interactions between corticostriatal and corticosubthalamic afferents on the one hand, and internal feedback circuits modulating BG output through the globus pallidus pars interna and substantia nigra pars reticulata on the other. In the normal BG network, the globus pallidus pars externa emerges as a main regulatory station of output activity. In the parkinsonian state, dopamine depletion shifts the BG toward inhibiting cortically generated movements by increasing the gain in the globus pallidus pars externa‐subthalamic nucleus‐globus pallidus pars interna network and reducing activity in “direct” cortico‐putaminal‐globus pallidus pars interna projections. Standard pharmacological treatments do not mimic the normal physiology of the dopaminergic system and, therefore, fail to restore a functional balance between corticostriatal afferents in the so‐called direct and indirect pathways, leading to the development of motor complications. This review emphasizes the concept that the BG can no longer be understood as a “go‐through” station in the control of movement, behavior, and emotions. The growing understanding of the complexity of the normal BG and the changes induced by DA depletion should guide the development of more efficacious therapies for Parkinson's disease. Ann Neurol 2008;64 (suppl):S30–S46