Cortical Network Modulation by Subthalamic Nucleus Deep Brain Stimulation

丘脑底核深部脑刺激(STN DBS)仍可提供实质性的运动益处 帕金森病(PD)患者的偶尔情绪和认知副作用。目前的文献假设 下游网络水平效应是STN DBS影响电机和非电机的关键机制 然而，我们检验这一假说的能力是有限的。常见的成像方式要么可以 没有必要的时间分辨率来辨别皮层网络的静息状态功能连接性 或者对植入DBS的患者来说不合适或不安全。我们开发了一种新型的高密度漫射 用于测量脑血流动力学的光学断层扫描(HD-DOT)系统，可以准确地映射 大脑皮质静息状态网络(RSN)或任务诱发反应在第一~1 cm内的功能连接 大脑皮层。HD-DOT的时间和空间分辨率与fMRI相当，比MRI或PET更舒适， 无辐射暴露，无电气伪影，无金属伪影，无禁忌症或安全顾虑 星展银行患者。我们有强有力的初步数据表明评估皮质RSNs的有效性和可行性 STN DBS患者的任务诱发反应。使用我们的新型HD-DOT系统，仔细的实验 设计和严格的分析，这项研究将确定大脑皮质RSN水平调制的性质 STN DBS及其与DBS诱导的运动和认知改变的关系。对照组和帕金森病患者 将在手术前登记，并进行HD-DOT和MRI(静息状态粗体，结构性)扫描。之后 植入和优化DBS，PD患者将在几种情况下进行HD-DOT扫描。使用 这些数据，我们将测试有关响应STN重要特征的网络的假设 DBS(例如，位置)及其与运动和非运动功能的关系。这一信息最终可能 提供更快优化DBS参数的方法并帮助识别大脑皮层节点或网络 参与STN DBS引起的益处或副作用，这将为侵入性较小的未来提供靶点 神经调节。最后，这项工作可以揭示大脑皮层网络生理学的基本属性，如 对上游扰动作出反应的塑性能力。

Deep brain stimulation of the subthalamic nucleus (STN DBS) can provide substantial motor benefit yet occasional mood and cognitive side effects in Parkinson disease (PD). Current literature hypothesizes that downstream network level effects are a critical mechanism of STN DBS’s influence on motor and non-motor behavior, however our ability to test this hypothesis has been limited. Common imaging modalities either do not have the temporal resolution necessary to discern resting state functional connectivity of cortical networks or are not suitable or safe for patients with implanted DBS. We have developed a novel high-density diffuse optical tomography (HD-DOT) system for measuring brain hemodynamics which can accurately map the functional connectivity of cortical resting state networks (RSN) or task-evoked responses within the first ~1cm of cortex. HD-DOT has comparable temporal and spatial resolution to fMRI, greater comfort than MRI or PET, no radiation exposure, no electrical artifacts, no metal artifacts and no contraindications or safety concerns for DBS patients. We have strong preliminary data showing the validity and feasibility of assessing cortical RSNs and task-induced responses in STN DBS patients. With our novel HD-DOT system, careful experimental design and rigorous analyses, this study will determine the nature of cortical RSN-level modulation induced by STN DBS and its relationship to DBS-induced motor and cognitive change. Controls and individuals with PD will be enrolled pre-surgically and scanned with HD-DOT and MRI (resting state BOLD, structural]). After implantation and optimization of DBS, PD individuals will be scanned with HD-DOT in several conditions. With these data, we will test hypotheses about networks that are responsive to important characteristics of STN DBS (e.g.location) and their relationship to motor and non-motor function. This information ultimately could provide methods for faster optimization of DBS parameters and help identify cortical nodes or networks involved in STN DBS-induced benefits or side effects that would provide future targets for less invasive neuromodulation. Finally, this work could reveal fundamental properties of cortical network physiology such as the capacity for plasticity in response to up-stream perturbations.