Cortical Network Modulation by Subthalamic Nucleus Deep Brain Stimulation

丘脑底核脑深部电刺激（DBS）可以提供实质性的运动益处， 帕金森病（PD）中偶尔的情绪和认知副作用。目前的文献假设， 下游网络水平效应是可再生能源对电动机和非电动机影响的关键机制 然而，我们测试这一假设的能力有限。常见的成像方式要么 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 或不适合植入DBS的患者或不安全。我们开发了一种新型的高密度扩散 光学断层扫描（HD-DOT）系统，用于测量脑血流动力学，可以准确地映射 皮层静息状态网络（RSN）或任务诱发反应的功能连接在第一个~1cm内 皮质HD-DOT具有与fMRI相当的时间和空间分辨率，比MRI或PET更舒适， 无辐射暴露，无电气伪影，无金属伪影，无禁忌症或安全性问题 DBS患者。我们有强有力的初步数据显示评估皮质RSN的有效性和可行性 和任务诱发的反应。通过我们新颖的HD-DOT系统，仔细的实验 设计和严格的分析，这项研究将确定皮质RSN水平调制诱导的性质， DBS及其与DBS诱导的运动和认知变化的关系。对照组和PD患者 将在术前入组，并使用HD-DOT和MRI（静息状态BOLD，结构）进行扫描。后 DBS植入和优化，PD个体将在几种条件下用HD-DOT扫描。与 这些数据，我们将测试有关网络的假设是响应的重要特征， DBS（例如位置）及其与运动和非运动功能的关系。这些信息最终可能 提供更快优化DBS参数的方法，并帮助识别皮质节点或网络 涉及到的好处或副作用，将提供未来的目标， 神经调节最后，这项工作可以揭示皮层网络生理学的基本特性， 对上游扰动的可塑性反应能力。

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.