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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 98/3/1675    most recent 00547.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Birdno, M. J. Articles by Grill, W. M. Search for Related Content PubMed PubMed Citation Articles by Birdno, M. J. Articles by Grill, W. M.

Pulse-to-Pulse Changes in the Frequency of Deep Brain Stimulation Affect Tremor and Modeled Neuronal Activity

¹Department of Biomedical Engineering, Duke University, Durham, North Carolina; and ²Center for Neurological Restoration and ³Neurological Surgery, Cleveland Clinic Foundation, Cleveland, Ohio

Submitted 15 May 2007; accepted in final form 15 July 2007

The effectiveness of deep brain stimulation (DBS) in relieving the symptoms of movement disorders is dependent on the average frequency of stimulation. However, no one has yet examined whether the effectiveness of DBS in relieving tremor is dependent on the pulse-to-pulse (instantaneous) frequency of DBS. We examined the effects of paired-pulse thalamic DBS on tremor in subjects with essential tremor and on the firing of model neurons in a biophysically based computational model of DBS. DBS with an average rate of 130 Hz was more effective at reducing tremor when pulses were evenly spaced than when there were large differences between intrapair and interpair pulse intervals. Similar correlations were observed in the firing patterns of model neurons: increasing the difference between the intrapair and interpair intervals rendered model neurons more likely to fire synchronous bursts, more likely to fire irregularly, and less likely to entrain to the stimulus. The tremor responses provide evidence that the pulse-to-pulse frequency of DBS, not just its average rate, plays an important role in DBS function. Modeling results also suggest that effective DBS overrides oscillatory pathological activity and replaces it with more regularized neuronal firing patterns.