Computational Models of Deep Brain Stimulation of the Cerebellothalamic and Subthalamopallidal Pathways

小脑丘脑和丘脑下苍白通路的深部脑刺激的计算模型

• 批准号: 9760012
• 负责人: Kelsey Bower
• 金额: $ 4.5万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9760012
• 关键词: Action Potentials; Age; Algorithms; Anatomic Models; Anatomy; Area; Axon; Brain region; Clinical; Cognitive; Computer Simulation; Data; Deep Brain Stimulation; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Electrodes; Elements; Enrollment; Ensure; Evaluation; FDA approved; Fellowship; Fiber; Generations; Geometry; Goals; Implant; Implanted Electrodes; Location; Magnetic Resonance Imaging; Measurement; Mediating; Modeling; Motor; Multimodal Imaging; Neural Pathways; Neurobehavioral Manifestations; Neurodegenerative Disorders; Outcome; Output; Parkinson Disease; Pathology; Pathway interactions; Patients; Population; Postoperative Period; Probability; Procedures; Quality of life; Research; STN stimulation; Scanning; Societies; Statistical Data Interpretation; Structure; Structure of subthalamic nucleus; System; Therapeutic; Therapeutic Effect; Tremor; Variant; X-Ray Computed Tomography; associated symptom; brain tissue; design; diencephalon; direct application; effective therapy; electric field; image registration; imaging Segmentation; improved; interest; motor symptom; nervous system disorder; relating to nervous system; response; side effect; social; theories; tractography; voltage

Project Summary/Abstract Parkinson’s disease is the second most common neurodegenerative disorder, with an estimated 59,000 new cases per year in the US, and as populations age it is expected to impose significant financial and social burden on society. Deep brain stimulation is an FDA approved treatment for PD, but despite a marked improvement in quality of life, DBS therapy is often inconsistent and can result in both cognitive and motor side effects. This may be due to a lack of understanding of the underlying mechanisms and structural pathways that mediate the therapeutic effects of DBS. This project seeks to identify the pathways responsible for the tremor improvements in STN DBS. In the long term, this research will refine DBS targeting and improve our overall understanding of the PD pathology. The first aim is to develop three-dimensional, patient-specific anatomical and tractography models. Ten patients and two fiber pathways will be modeled. Magnetic resonance images (MRI) will be used to define the geometry of relevant structures and the trajectory of relevant fiber pathways (i.e. cerebellothalamic and subthalamopallidal pathways), and computed tomography scans will be used to determine the location of the DBS electrode. This will result in ten patient-specific computational anatomical models including fiber tractography for use in DBS modeling. The second aim is to identify stimulation parameters that preferentially activate each specific pathway. Axons will be modeled using cable theory and their trajectories will be determined by probabilistic tractography. Multivariate statistical analyses will be used to analyze axon activation in response to stimulation. A numerical optimization algorithm will be used to determine specific stimulation paradigms that preferentially activate one pathway (i.e. the cerebellothalamic or subthalamopallidal pathway). The outcome of this aim will be a set of patient-specific stimulation parameters that will theoretically preferentially activate a specific fiber pathway. The third aim is to evaluate the clinical outcomes of these selective stimulation paradigms with regard to tremor to determine the effects of activation of each pathway. Quantitative motor assessments will be performed to assess preferential activation outcomes. We hypothesize that preferential activation of specific fiber pathways will result in different clinical outcomes, including variation in therapeutic benefit. Further, we hypothesize that modulation of the cerebellothalamic pathway is necessary and sufficient for tremor control. The completion of this aim will result in an improved understanding of the outcomes associated with preferential activation of the cerebellothalamic and subthalamopallidal pathways. Successful completion of this research will advance our understanding of how activation of specific fiber pathways can produce a therapeutic effect in PD patients.

项目概要/摘要 帕金森病是第二常见的神经退行性疾病，美国每年估计有 59,000 例新发病例，随着人口老龄化，预计会给社会带来巨大的经济和社会负担。深部脑刺激是 FDA 批准的帕金森病治疗方法。尽管生活质量显着改善，但 DBS 治疗往往不一致，并可能导致认知和运动副作用，这可能是由于缺乏对介导 DBS 治疗效果的潜在机制和结构途径的了解。该项目旨在确定导致 STN DBS 震颤改善的途径 从长远来看，这项研究将完善 DBS 靶向并提高我们对 PD 病理学的整体理解。 第一个目标是开发三维、患者特定的解剖和纤维束成像模型，将使用磁共振图像 (MRI) 来定义相关结构的几何形状和相关纤维的轨迹。通路（即小脑丘脑和丘脑下丘脑通路）和计算机断层扫描将用于确定 DBS 电极的位置，这将产生 10 个患者特定的计算解剖模型，包括纤维。用于 DBS 建模的纤维束成像。 第二个目标是确定优先激活每个特定通路的刺激参数。 轴突将使用电缆理论进行建模，其轨迹将通过概率纤维束描记术确定，将用于分析轴突对刺激的激活，将使用数值优化算法来确定优先激活一条通路的特定刺激范例（即小脑丘脑或丘脑下丘脑通路）。该目标的结果将是一组患者特定的刺激参数，理论上将优先激活特定的纤维通路。 第三个目标是评估这些选择性刺激范例在震颤方面的临床结果，以确定每个通路激活的效果，以评估优先激活结果。导致不同的临床结果，包括治疗效果的变化。此外，我们认为调节小脑丘脑通路对于震颤控制是必要且充分的。这一目标的完成将导致更好地理解与优先激活相关的结果。小脑丘脑和丘脑下丘脑通路。 这项研究的成功完成将加深我们对特定纤维通路的激活如何对帕金森病患者产生治疗效果的理解。