Use of Resting-State Networks to Predict the Ideal Site for Brain Stimulation

描述（由申请人提供）：局灶性脑刺激，包括脑深部电刺激（DBS）和重复性经颅磁刺激（rTMS），可对越来越多的脑部疾病患者（包括帕金森氏症、卒中后缺陷，甚至潜在的最低意识状态）产生治疗获益。然而，对于给定的患者或疾病，通常不清楚什么样的刺激部位最有效，从而限制了疗效和对新疾病的扩展。选择理想的刺激部位是困难的，部分原因是局灶性脑刺激通过连接传播以影响大脑区域的分布式网络，并且这些网络效应可以决定临床反应。因此，决定在哪里刺激部分取决于我们预测刺激将传播到哪里的能力。神经成像技术的进步，例如静息状态功能连接性MRI（rs-fcMRI），使我们能够以前所未有的清晰度可视化人类的大脑网络。该项目测试的假设是，通过rs-fcMRI观察到的网络可以预测局灶性脑刺激将如何传播，从而促进选择理想的刺激部位，以最终针对特定患者的特定网络。我建议在运动网络中测试这一假设，其中可以用经颅磁刺激（TMS）测量局灶性脑刺激的传播。对初级运动皮层（M1）的TMS导致可测量的肌肉收缩，其强度取决于M1中的潜在神经元活动。如果将TMS应用于连接的区域，然后传播到并改变M1，它将影响TMS诱导的肌肉收缩的强度。因此，本研究将检查rs-fcMRI是否可以用于识别TMS的影响将以可预测的方式传播到M1并影响M1的部位。它将进一步阐明rs-fcMRI的哪些特性最有用，以及基于个体化rs-fcMRI模式选择的刺激部位是否上级基于组数据选择的刺激部位。如果该项目成功，未来的努力将扩展该方法，以确定TMS和DBS站点最有可能具体影响与不同疾病有关的网络。潜在的应用包括识别最有可能传播到注意力网络并改善空间忽视的顶叶TMS位点，最有可能影响运动网络而不影响帕金森病患者的认知或情绪网络的DBS位点，或最有可能影响涉及唤醒和意识的网络的最低意识状态中的候选刺激位点。

DESCRIPTION (provided by applicant): Focal brain stimulation, including deep brain stimulation (DBS) and repetitive trans cranial magnetic stimulation (rTMS), can have therapeutic benefit in patients with an increasing number of brain disorders including Parkinson's, post-stroke deficits, and potentially even minimally conscious states. However it is often unclear what stimulation site will work best for a given patient or disease, limiting efficacy and extension to new disorders. Choosing an ideal stimulation site is difficult in part because focal brain stimulation propagates through connections to impact a distributed network of brain regions, and these network effects can determine the clinical response. Thus deciding where to stimulate depends in part on our ability to predict where stimulation will propagate. Advances in neuroimaging technology, such as resting-state functional connectivity MRI (rs-fcMRI) allow us to visualize brain networks in humans with unprecedented clarity. This project tests the hypothesis that networks seen with rs-fcMRI can predict how focal brain stimulation will propagate, thus facilitating selection of an ideal stimulation site to eventually target specific networks in specific patients. I propose to test this hypothesis in the motor network, where propagation of focal brain stimulation can be measured with transcranial magnetic stimulation (TMS). TMS to primary motor cortex (M1) results in a measurable muscle contraction, the strength of which depends on the underlying neuronal activity in M1. If one applies TMS to a connected region that then propagates to and alters M1, it will impact the strength of the TMS-induced muscle contraction. The current study will therefore examine whether rs-fcMRI can be used to identify sites from which the effects of TMS will propagate to and affect M1 in a predictable manner. It will further clarify what properties of rs-fcMRI are most useful and whether stimulation sites selected based on individualized rs-fcMRI patterns are superior to those selected based on group data. If this project is successful, future efforts will extend the approach to identify TMS and DBS sites most likely to specifically affect networks implicated in different diseases. Potential applications include identifying parietal TMS sites most likely to propagate to attention networks and improve spatial neglect, DBS sites most likely to impact motor networks without affecting cognitive or mood networks in a patient with Parkinson's, or candidate stimulation sites in minimally conscious states most likely to impact networks involved in arousal and consciousness.