Systems Level Model of Deep Brain Stimulation

深部脑刺激的系统级模型

• 批准号: 6922234
• 负责人: Cameron McIntyre
• 金额: $ 33.3万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6922234
• 关键词: Macaca mulatta; Parkinson' s disease; abnormal involuntary movement; behavior test; brain electrical activity; cell type; diffusion magnetic resonance imaging; electric field; electrodes; electrostimulus; histology; mathematics; model design /development; nervous system disorder therapy; neuroanatomy; neurons; neurophysiology; neuropsychology; nonhuman therapy evaluation; physical model; subthalamus

DESCRIPTION (provided by applicant): Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has rapidly emerged as an effective treatment in medically refractory Parkinson's disease (PD). However, our understanding of the effects of DBS is limited and future attempts at optimizing electrode design or stimulation parameters will depend on defining the mechanisms by which DBS achieves its therapeutic effect. The central hypothesis of the planned work is that DBS generates heterogeneous patterns of activation and inhibition in the different neuron types (local cells, fibers of passage, afferent inputs) that surround the electrode and these stimulation effects are transmitted throughout the interconnected nuclei of the basal ganglia. We further hypothesize that therapeutic and non-therapeutic stimulation result in different patterns of activation in the different neuron types and we can modulate the activation of specific neuron types via alterations in the stimulation parameters. In turn, our goal is to assess the therapeutic importance of different neural activation patterns on the behavioral and neurophysiological effects of DBS. To accomplish this goal we will develop a systems level model of DBS that will be coupled to ongoing experimental work using DBS of the parkinsonian macaque (R01-NS37019, PI: J. Vitek). The first specific aim will generate realistic field-neuron models of the electric field generated by DBS, and the different neuron types influenced by stimulation. The second and third specific aims will couple the field-neuron model to hypothesis driven research experiments with quantitative predictions of the effects of DBS as a function of the stimulation parameters. This work will provide fundamental knowledge necessary for the advancement of DBS technology for treatment of PD in the human, and may also enhance the application of DBS to other disorders such as dystonia, epilepsy, obsessive-compulsive disorder, and major depression.

描述（由申请人提供）：丘脑底核（STN）的深部脑刺激（DBS）已迅速成为医学难治性帕金森病（PD）的有效治疗方法。然而，我们对 DBS 效果的理解是有限的，未来优化电极设计或刺激参数的尝试将取决于确定 DBS 实现其治疗效果的机制。计划工作的中心假设是，DBS 在电极周围的不同神经元类型（局部细胞、通道纤维、传入输入）中产生异质的激活和抑制模式，并且这些刺激效果通过基底神经节的互连核传递。我们进一步假设治疗性和非治疗性刺激会导致不同神经元类型的不同激活模式，并且我们可以通过改变刺激参数来调节特定神经元类型的激活。反过来，我们的目标是评估不同神经激活模式对 DBS 的行为和神经生理学影响的治疗重要性。为了实现这一目标，我们将开发一个 DBS 系统级模型，该模型将与正在进行的帕金森猕猴 DBS 实验工作（R01-NS37019，PI：J. Vitek）相结合。第一个具体目标是生成 DBS 产生的电场的真实场神经元模型，以及受刺激影响的不同神经元类型。第二个和第三个具体目标是将场神经元模型与假设驱动的研究实验结合起来，定量预测 DBS 的效果作为刺激参数的函数。这项工作将为发展 DBS 技术治疗人类 PD 提供必要的基础知识，并且还可能增强 DBS 在肌张力障碍、癫痫、强迫症和重度抑郁症等其他疾病中的应用。