Movement-related discharge in the macaque globus pallidus during high-frequency stimulation of the subthalamic nucleus.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) has largely replaced ablative therapies for Parkinson's disease. Because of the similar efficacies of the two treatments, it has been proposed that DBS acts by creating an "informational lesion," whereby pathologic neuronal firing patterns are replaced by low-entropy, stimulus-entrained firing patterns. The informational lesion hypothesis, in its current form, states that DBS blocks the transmission of all information from the basal ganglia, including both pathologic firing patterns and normal, task-related modulations in activity. We tested this prediction in two healthy rhesus macaques by recording single-unit spiking activity from the globus pallidus (232 neurons) while the animals completed choice reaction time reaching movements with and without STN-DBS. Despite strong effects of DBS on the activity of most pallidal cells, reach-related modulations in firing rate were equally prevalent in the DBS-on and DBS-off states. This remained true even when the analysis was restricted to cells affected significantly by DBS. In addition, the overall form and timing of perimovement modulations in firing rate were preserved between DBS-on and DBS-off states in the majority of neurons (66%). Active movement and DBS had largely additive effects on the firing rate of most neurons, indicating an orthogonal relationship in which both inputs contribute independently to the overall firing rate of pallidal neurons. These findings suggest that STN-DBS does not act as an indiscriminate informational lesion but rather as a filter that permits task-related modulations in activity while, presumably, eliminating the pathological firing associated with parkinsonism.
Department of Neurobiology, Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, and.
Andrew J
AJ
Zimnik
Department of Neurobiology, Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, and.
Gerald J
GJ
Nora
Centre for Cognitive Neuroscience, UMR5229, CNRS, 67 Boulevard Pinel 69500 Bron, France.
Michel
M
Desmurget
Department of Neurobiology, Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, and rturner@pitt.edu.
Robert S
http://orcid.org/0000-0002-6074-4365
RS
Turner
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D046690:Deep Brain Stimulation; D019277:Entropy; D005917:Globus Pallidus / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D009068:Movement / Q000502:physiology*; D020531:Subthalamic Nucleus / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
basal ganglia; nonhuman primate; reaching