Improved Efficacy of Temporally Non-Regular Deep Brain Stimulation in Parkinson's Disease

• Type of Material: Article
• Authors: David T. Brocker, Duke University; Brandon D. Swan, Duke University; Dennis A. Turner, Duke University; Robert Gross, Emory University; Stephen B. Tatter, Wake Forest University; Mandy Miller Koop, Stanford University; Helen Bronte-Stewart, Stanford University; Warren M. Grill, Duke University
• Language: English
• Date: 2013-01-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.expneurol.2012.09.008
• Title of Journal or Parent Work: Experimental Neurology
• ISSN: 0014-4886
• Volume: 239
• Issue: 1
• Start Page: 60
• End Page: 67
• Grant/Funding Information: This research was supported by National Institutes of Health [R01 NS40894 to W.M.G.]; and the Robert Plonsey Fellowship from the Duke University Department of Biomedical Engineering [to D.T.B.].
• Keywords: Neurosciences; Bradykinesia; HIGH-FREQUENCY STIMULATION; BRADYKINESIA; Beta frequency oscillations; Neurosciences & Neurology; MODEL; STIMULUS PARAMETERS; SUBTHALAMIC NUCLEUS STIMULATION; PALLIDAL STIMULATION; Parkinson's disease; TREMOR; Science & Technology; BASAL GANGLIA; Deep brain stimulation; Life Sciences & Biomedicine; NEURONAL-ACTIVITY; PATHOPHYSIOLOGY
• Research Categories: Engineering, Biomedical; Biology, Neuroscience

Abstract

High frequency deep brain stimulation is an effective therapy for motor symptoms in Parkinson's disease. However, the relative clinical efficacy of regular versus non-regular temporal patterns of stimulation in Parkinson's disease remains unclear. To determine the temporal characteristics of non-regular temporal patterns of stimulation important for the treatment of Parkinson's disease, we compared the efficacy of temporally regular stimulation with four non-regular patterns of stimulation in subjects with Parkinson's disease using an alternating finger tapping task. The patterns of stimulation were also evaluated in a biophysical model of the parkinsonian basal ganglia that exhibited prominent oscillatory activity in the beta frequency range. The temporal patterns of stimulation differentially improved motor task performance. Three of the non-regular patterns of stimulation improved performance of the finger tapping task more than temporally regular stimulation. In the computational model all patterns of deep brain stimulation suppressed beta band oscillatory activity, and the degree of suppression was strongly correlated with the clinical efficacy across stimulation patterns. The three non-regular patterns of stimulation that improved motor performance over regular stimulation also suppressed beta band oscillatory activity in the computational model more effectively than regular stimulation. These data demonstrate that the temporal pattern of stimulation is an important consideration for the clinical efficacy of deep brain stimulation in Parkinson's disease. Furthermore, non-regular patterns of stimulation may ameliorate motor symptoms and suppress pathological rhythmic activity in the basal ganglia more effectively than regular stimulation. Therefore, non-regular patterns of deep brain stimulation may have useful clinical and experimental applications.