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Deep Brain Stimulation of the Globus Pallidus Internus in the Parkinsonian Primate: Local Entrainment and Suppression of Low-Frequency Oscillations

¹Departments of Neurobiology and Bioengineering and The Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania; ²Department of Neurological Surgery, University of California, San Francisco, San Francisco, California; and ³Department of Biological Sciences, The Open University, Milton Keynes, United Kingdom

Submitted 30 September 2008; accepted in final form 15 January 2009

Competing theories seek to account for the therapeutic effects of high-frequency deep brain stimulation (DBS) of the internal globus pallidus (GPi) for medically intractable Parkinson's disease. To investigate this question, we studied the spontaneous activity of 102 pallidal neurons during GPiDBS in two macaques rendered parkinsonian by administration of MPTP. Stimulation through macroelectrodes in the GPi (200 µA at 150 Hz for 30 s) reduced rigidity in one animal and increased spontaneous movement in both. Novel artifact subtraction methods allowed uninterrupted single-unit recording during stimulation. GPiDBS induced phasic (78% of cells) or sustained (22%) peristimulus changes in firing in both pallidal segments. A subset of cells responded at short latency (<2 ms) in a manner consistent with antidromic driving. Later phasic increases clustered at 3- to 5-ms latency. Stimulation-induced decreases were either phasic, clustered at 1–3 ms, or sustained, showing no peristimulus modulation. Response latency and magnitude often evolved over 30 s of stimulation, but responses were relatively stable by the end of that time. GPiDBS reduced mean firing rates modestly and only in GPi (–6.9 spikes/s). Surprisingly, GPiDBS had no net effect on the prevalence or structure of burst firing. GPiDBS did reduce the prevalence of synchronized low-frequency oscillations. Some cell pairs became synchronized instead at the frequency of stimulation. Suppression of low-frequency oscillations did not require high-frequency synchronization, however, or even the presence of a significant peristimulus response. In summary, the therapeutic effects of GPiDBS may be mediated by an abolition of low-frequency synchronized oscillations as a result of phasic driving.

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				Y. Erez, H. Czitron, K. McCairn, K. Belelovsky, and I. Bar-Gad Short-Term Depression of Synaptic Transmission during Stimulation in the Globus Pallidus of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Primates J. Neurosci., June 17, 2009; 29(24): 7797 - 7802. [Abstract] [Full Text] [PDF]