Effects of transient focal inactivation of the basal ganglia in parkinsonian primates.
Ablative and chronic stimulation procedures targeting the internal pallidum (GPi) and the subthalamic nucleus (STN) have led to major advancements in the treatment of Parkinson's disease and other movement disorders. Although these procedures have evolved to primarily target the posterior ventrolateral sensorimotor portion of GPi and to less selectively target STN, centrally, the ideal targets within these structures remain to be fully established. In this study, we sought to identify the optimal targeting sites in GPi and STN for reversal of parkinsonian signs through a series of reversible injections of the GABA(A) agonist muscimol in these nuclei in parkinsonian primates. Akinesia and bradykinesia were strongly ameliorated by discrete inactivation within the centromedial extent of the sensorimotor territory in GPi and the lateral portion of the sensorimotor territory in STN. This suggests that akinesia and bradykinesia might, in fact, originate from abnormalities in the same, or at least overlapping, motor circuits in the parkinsonian state. Inactivation of areas outside of the motor territories did not improve parkinsonism but induced circling and behavioral abnormalities. The segregation of basal ganglia-thalamocortical circuits appears to be therefore maintained, at least to a large extent, in the parkinsonian state. These results underscore that inactivation of discrete regions in the central territory of GPi and the lateral portion of STN are sufficient to ameliorate parkinsonian motor signs and that extension of lesions into nonmotor territories may be deleterious. Surgical outcomes might therefore be optimized by placing more discrete lesions and by restricting the extent of chronic stimulation.
Baron
Mark S
MS
Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. msbaron@emory.edu
Wichmann
Thomas
T
Ma
Demin
D
DeLong
Mahlon R
MR
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D018755:GABA Agonists / Q000008:administration & dosage*; D005917:Globus Pallidus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D018476:Hypokinesia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D008253:Macaca mulatta; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000008:administration & dosage*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome
D018755:GABA Agonists; D009118:Muscimol; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine