Pathway targeted deep brain stimulation for Parkinson's disease

项目总结 丘脑深部电刺激(DBS)是治疗帕金森病(PD)的一种有效方法。 然而，人们对具体的神经通路(S)负责治疗的好处知之甚少。直接 刺激超直接通路和/或丘脑底核通路代表了两个最大的 有可能成为“目标”的候选人。因此，该项目的目标是结合患者特定的7T成像 和神经刺激模型一起使用，从而能够以概率方式识别与 丘脑下部DBS患者记录的临床结果指标的变化。这项研究将依靠 指导对30例丘脑DBS患者进行临床测试的纤维束成像激活模型(TAMS)。 我们的多学科方法将整合神经成像、神经刺激建模、 以及量化的临床结果衡量标准，为这些患者定制DBS。第一个目标将获得高- 种植体手术前的7T磁共振分辨率数据。这些图像将提供无与伦比的解剖学 每个病人的特征。第二个目标是为每个受试者创建针对患者的TAM。这些 模型将使我们能够定义理论上的最佳设置，以集中激活任何一个超直接 通路或丘脑下丘脑-苍白球通路。第三个目标是量化临床结果。 刺激参数由或传统临床实践确定。这些临床结果将是 再加上的预测，创建了一个概率地形图-激活地图集 丘脑下部区域。这项研究的结果将有助于确定DBS的最佳植入位置 电极，并实现刺激参数设置的理论预测，这些参数设置将激活集中在 靶向途径和/或避免副作用途径。

PROJECT SUMMARY Subthalamic deep brain stimulation (DBS) is an effective for the treatment of Parkinson's disease (PD). However, little is known about the specific neural pathway(s) responsible for therapeutic benefit. Direct stimulation of either the hyperdirect pathway and/or the subthalamopallidal pathway represents two of the most likely candidates as the "target". Therefore, the goal of this project is to combine patient-specific 7T imaging and neurostimulation models together to enable probabilistic identification of the stimulation pathways linked to changes in clinical outcome measures recorded from subthalamic DBS patients. This study will rely on tractography-activation models (TAMs) to guide clinical testing on a cohort of 30 subthalamic DBS patients. Our multi-disciplinary approach will integrate the latest advances in neuroimaging, neurostimulation modeling, and quantitative clinical outcome measures to customize DBS to these patients. The first aim will acquire high- resolution 7T MRI data prior to their implant surgery. These images will provide unparalleled anatomical characterization of each patient. The second aim will create patient-specific TAMs for each subject. These models will enable us to define theoretically optimal settings for focused activation of either the hyperdirect pathway or the subthalamopallidal pathway. The third aim will quantify the clinical outcomes achieved with stimulation parameters defined by either the TAM or traditional clinical practice. These clinical results will be coupled with the TAM predictions to create a probabilistic tractography-activation atlas (PTAA) for the subthalamic region. The results of this study will help identify optimal implantation locations for DBS electrodes, and enable theoretical prediction of stimulation parameter settings that focus activation on the targeted pathways and/or avoid side-effect pathways.