Comparison of Unilateral and Bilateral Subthalamic Stimulation in Parkinson's

描述（由申请人提供）：脑深部电刺激（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。已证明双侧DBS会产生认知缺陷，这是对某些PD患者进行该手术的禁忌症。由于大多数日常活动由同时进行的认知和运动组成，因此可以预测，即使在成功进行手术的患者中，认知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，因此可能低估了认知和运动功能的缺陷。我们已经表明，认知和认知运动功能受到损害的程度更大，在双边，相比，单边的DBS。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电流扩散到小脑的非运动区域，从而减轻认知下降，同时保持运动益处。基于这些发现，我们假设，电流传播到小脑的非运动区域会破坏基底神经节内的认知信息处理，并产生在小脑深部电刺激期间观察到的认知下降，从而导致运动表现下降。我们进一步假设，最大限度地增加电流在感觉运动区的扩散，同时最大限度地减少扩散到非运动区的运动将减轻认知能力下降，而不损害运动功能的增益。将使用临床认知和运动测试以及认知-运动双任务范式（即工作记忆任务与上肢力跟踪任务配对）同时量化认知和运动表现。将从48例接受双侧DBS的晚期PD患者中收集数据，这些患者在三种条件下接受DBS：1）DBS前，2）DBS后，使用临床定义的DBS参数，3）DBS后，使用模型导出的参数，其中最大限度地减少了DBS非运动区域内的组织激活（VTA）体积。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，本项目中开发的技术和方法可以帮助标准化临床程控过程，特别是在DBS程控细微差别方面缺乏丰富经验和专业知识的中心。公共卫生相关性：本项目的目标是评估帕金森病（PD）患者在单任务和双任务条件下接受单侧与双侧丘脑底核（DBS）脑深部电刺激（DBS）的认知和运动表现，并预测双侧丘脑底核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程控参数，这些参数将最大限度地减少电流扩散到小脑的非运动区域，以降低认知障碍的水平，同时保持运动功能的改善。这种双任务模式和可视化软件的结合使用有可能使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.