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Origins and suppression of oscillations in a computational model of Parkinson’s disease

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Abstract

Efficacy of deep brain stimulation (DBS) for motor signs of Parkinson’s disease (PD) depends in part on post-operative programming of stimulus parameters. There is a need for a systematic approach to tuning parameters based on patient physiology. We used a physiologically realistic computational model of the basal ganglia network to investigate the emergence of a 34 Hz oscillation in the PD state and its optimal suppression with DBS. Discrete time transfer functions were fit to post-stimulus time histograms (PSTHs) collected in open-loop, by simulating the pharmacological block of synaptic connections, to describe the behavior of the basal ganglia nuclei. These functions were then connected to create a mean-field model of the closed-loop system, which was analyzed to determine the origin of the emergent 34 Hz pathological oscillation. This analysis determined that the oscillation could emerge from the coupling between the globus pallidus external (GPe) and subthalamic nucleus (STN). When coupled, the two resonate with each other in the PD state but not in the healthy state. By characterizing how this oscillation is affected by subthreshold DBS pulses, we hypothesize that it is possible to predict stimulus frequencies capable of suppressing this oscillation. To characterize the response to the stimulus, we developed a new method for estimating phase response curves (PRCs) from population data. Using the population PRC we were able to predict frequencies that enhance and suppress the 34 Hz pathological oscillation. This provides a systematic approach to tuning DBS frequencies and could enable closed-loop tuning of stimulation parameters.

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Acknowledgments

Supported by MnDrive Fellowship, National Science Foundation IGERT DGE-1069 104, NSF Collaborative research grant 1264432, Medtronic, Netoff CAREER 0954797, Neuroscience R21 institutional training grant 2T32GM008471.

Conflict of interest

Research was funded in part by Medtronic.

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  1. Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN, 55455, USA

    Abbey B. Holt

  2. Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, 55455, USA

    Theoden I. Netoff

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Holt, A.B., Netoff, T.I. Origins and suppression of oscillations in a computational model of Parkinson’s disease. J Comput Neurosci 37, 505–521 (2014). https://doi.org/10.1007/s10827-014-0523-7

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