Comparison of Unilateral and Bilateral Subthalamic Stimulation in Parkinson's

描述（由申请人提供）：深部脑刺激（DBS）是一种外科手术，可有效改善晚期帕金森病（PD）的主要运动体征。双侧 STN DBS 已被证明会产生认知缺陷，这是对某些 PD 患者进行此手术的禁忌症。由于大多数日常活动由同时进行的认知和运动部分组成，因此可以预测，即使在手术成功实施的患者中，认知能力下降也可能会损害其改善的运动功能。尚未研究这些下降对运动功能的潜在影响，因为目前的临床评估没有同时检查认知和运动功能，因此可能低估认知和运动功能的缺陷。我们已经证明，与单侧 STN DBS 相比，双侧 STN DBS 的认知和认知运动功能受到更大程度的损害。初步数据表明，选择 DBS 参数的神经计算方法可以最大限度地减少 STN 非运动区域的电流扩散，从而减轻认知能力下降，同时保持运动益处。基于这些发现，我们假设电流向 STN 非运动区域的传播扰乱了基底神经节内认知信息的处理，并导致 STN DBS 期间观察到的认知能力下降，从而导致运动性能下降。我们进一步假设，最大化 STN 感觉运动区域的电流扩散，同时最小化 STN 非运动区域的电流扩散，将减轻认知能力下降，而不影响运动功能的增益。临床认知和运动测试以及认知-运动双任务范例（即工作记忆任务与上肢力跟踪任务配对）将用于同时量化认知和运动表现。数据将从 48 名接受双侧 STN DBS 的晚期 PD 患者中收集，涉及三种情况：1) DBS 前，2) DBS 后具有临床定义的 DBS 参数，3) DBS 后具有模型导出的参数，其中 STN 非运动区域内的组织激活体积 (VTA) 最小化。该项目的结果可能会改善与 DBS 相关的认知运动结果，并提高这些患者的生活质量。此外，该项目开发的技术和方法可以帮助标准化临床规划过程，特别是在 DBS 规划的细微差别方面缺乏丰富经验和专业知识的中心。公共健康相关性：该项目的目标是评估单侧和双任务条件下单侧与双侧丘脑底核 (STN) 深部脑刺激 (DBS) 下帕金森病 (PD) 患者的认知和运动表现，并预测 STN 运动和非运动区域激活的组织体积与双任务条件下认知和运动功能变化之间的关系。然后，这些结果将用于选择编程参数，最大限度地减少进入 STN 非运动区域的电流扩散，以降低认知障碍水平，同时保持运动功能的改善。这种双任务范例和可视化软件的结合使用有可能让临床医生更好地实现 DBS 的基本目标：提供最大的运动反应，同时最大限度地减少认知运动损失。

DESCRIPTION (provided by applicant): Deep brain stimulation (DBS) is a surgical procedure that is effective in improving the cardinal motor signs of advanced Parkinson's disease (PD). Bilateral STN DBS has been shown to produce cognitive deficits which are a contraindication for performing this procedure on some PD patients. Because most daily activities consist of cognitive and motor components that are performed concurrently, it would be predicted that even in those patients in whom the procedure is performed successfully, it is likely that cognitive declines will compromise their improved motor function. The potential effects of these declines on motor function have not been studied as current clinical assessments do not examine cognitive and motor function simultaneously and may therefore underestimate the deficits in cognitive and motor function. We have shown that cognitive and cognitive-motor function is compromised to a greater extent during bilateral, compared to unilateral STN DBS. Preliminary data indicate a neurocomputational approach to the selection of DBS parameters that minimizes current spread into non-motor regions of the STN mitigates cognitive declines while motor benefits are maintained. Based on these findings, we hypothesize that the spread of current to non-motor regions of the STN disrupts the processing of cognitive information within the basal ganglia and produces the cognitive declines observed during STN DBS which leads to diminished motor performance. We further hypothesize that maximizing current spread in the sensorimotor region of the STN while minimizing spread to non-motor regions of the STN will mitigate cognitive declines without compromising gains in motor function. Clinical cognitive and motor testing and a cognitive-motor dual-task paradigm (i.e. working memory task paired with a upper extremity force-tracking task) will be used to simultaneously quantify cognitive and motor performance. Data will be collected from 48 advanced PD patients undergoing bilateral STN DBS across three conditions: 1) pre-DBS, 2) post-DBS with clinically defined DBS parameters and 3) post-DBS with model derived parameters in which the volume of tissue activated (VTA) within the non-motor region of the STN is minimized. The results from this project will likely improve the cognitive-motor outcomes associated with DBS and enhance the quality of life for those patients. In addition, the technology and methodology developed in this project could help standardize the process of clinical programming, especially at centers lacking extensive experience and expertise in the nuances of DBS programming. PUBLIC HEALTH RELEVANCE: The goals of this project are to assess cognitive and motor performance in Parkinson's disease (PD) patients under unilateral compared to bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) during single- and dual-task conditions and to predict the relationship between the volume of tissue activated in the motor and non-motor regions of the STN and changes in cognitive and motor function under dual-task conditions. These results will then be used to select programming parameters that will minimize spread of current into non-motor regions of the STN to reduce the level of cognitive impairment while maintaining improvements in motor function. The combined use of this dual-task paradigm and visualization software has the potential to allow clinicians to better achieve the fundamental goal of DBS: provide maximal motor response while minimizing cognitive-motor losses.