Comparison of Unilateral and Bilateral Subthalamic Stimulation in Parkinson's

描述(申请人提供)：脑深部刺激(DBS)是一种外科手术，能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障碍，这是对一些PD患者进行这一手术的禁忌症。由于大多数日常活动由同时进行的认知和运动部分组成，可以预测，即使在那些手术成功的患者中，认知能力的下降也很可能会损害他们改善的运动功能。这些下降对运动功能的潜在影响尚未被研究，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，与单侧STN DBS相比，双侧STN DBS期间认知和认知运动功能的损害程度更大。初步数据表明，一种神经计算方法来选择DBS参数，最大限度地减少电流扩散到STN的非运动区，在保持运动优势的同时缓解认知衰退。基于这些发现，我们假设电流扩散到STN的非运动区扰乱了基底节内认知信息的处理，并产生了STN DBS期间观察到的认知衰退，从而导致运动能力下降。我们进一步假设，最大限度地扩大STN感觉运动区的电流扩散，同时最小化STN非运动区的电流扩散，将在不影响运动功能的基础上缓解认知衰退。临床认知和运动测试以及认知-运动双重任务范式(即工作记忆任务与上肢力量跟踪任务配对)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患者收集，包括三种情况：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STN非运动区内的组织激活(VTA)体积最小。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，在该项目中开发的技术和方法可以帮助标准化临床规划过程，特别是在缺乏在星展银行规划细微差别方面的广泛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在单侧和双侧丘脑底核(STN)脑深部刺激(DBS)条件下的认知和运动表现，并预测双任务条件下STN运动和非运动区激活的组织体积与认知和运动功能变化的关系。这些结果将被用于选择编程参数，这些参数将最大限度地减少电流传播到STN的非运动区，以降低认知损害水平，同时保持运动功能的改善。这种双重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：在提供最大运动反应的同时将认知运动损失降至最低。

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.