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Tremor reduction and modeled neural activity during cycling thalamic deep brain stimulation.

ABSTRACT: The effectiveness of deep brain stimulation (DBS) depends on both the frequency and the temporal pattern of stimulation. We quantified responses to cycling DBS with constant frequency to determine if there was a critical on and/or off time for alleviating tremor.We measured postural tremor in 10 subjects with thalamic DBS and quantified neuronal entropy in a network model of Vim thalamic DBS. We tested 12 combinations of cycling on/off times that maintained the same average frequency of 125 Hz, four constant frequency settings, and baseline.Tremor and neural firing pattern entropy decreased as the percent on time increased from 50% to 100%. Cycling with stimulation on for at least 60% of the time was as effective as regular stimulation. All cycling settings reduced the firing pattern entropy of model neurons from the no stimulation condition by regularizing pathological firing patterns, either through synaptically-mediated inhibition or axon excitation.These results indicate that pauses present in cycling stimulation decreased its effectiveness in suppressing tremor, and that changes in the amount of tremor suppression were strongly correlated with changes in the firing pattern entropy of model neurons.Cycling stimulation may reduce power consumption during clinical DBS, and thereby increase the battery life of the implanted pulse generator.

SUBMITTER: Kuncel AM

PROVIDER: S-EPMC3261319 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Tremor reduction and modeled neural activity during cycling thalamic deep brain stimulation.

Kuncel Alexis M AM Birdno Merrill J MJ Swan Brandon D BD Grill Warren M WM

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 20111005 5

<h4>Objective</h4>The effectiveness of deep brain stimulation (DBS) depends on both the frequency and the temporal pattern of stimulation. We quantified responses to cycling DBS with constant frequency to determine if there was a critical on and/or off time for alleviating tremor.<h4>Methods</h4>We measured postural tremor in 10 subjects with thalamic DBS and quantified neuronal entropy in a network model of Vim thalamic DBS. We tested 12 combinations of cycling on/off times that maintained the ...[more]

PMID: 21978653

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Project description:The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

Dataset Information

Tremor reduction and modeled neural activity during cycling thalamic deep brain stimulation.

Publications

Tremor reduction and modeled neural activity during cycling thalamic deep brain stimulation.

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