Role of functional brain connectivity on efficacy of TMS for depression

描述（由申请人提供）：经颅磁刺激（TMS）左背外侧前额叶皮层（DLPFC）可用于治疗抑郁症，Neuronetics（R）的Neurostar TMS方案于2008年10月被美国食品和药物管理局批准用于治疗某些形式的抗药性抑郁症。然而，临床反应是异质性的，效应量可能有限。已知导致这种反应变异性的一个因素是DLPFC内和周围的特定刺激部位的差异。我们实验室的最新证据表明，不同DLPFC靶点的疗效与每个靶点与更深边缘区的连接有关，特别是 膝下扣带基于这些发现，我们提出了一种新的基于连接性的靶向方法，以确定个体患者的最佳刺激部位，以最大限度地提高抗抑郁反应。本项目的目标是在接受TMS治疗抑郁症的实际患者中实证验证这种方法。 由精神科医生转诊治疗并符合FDA批准的Neurostar TMS方案的患者将有资格参加本研究。参与者将在为期四周的TMS治疗疗程（连续四周的周一至周五每日疗程）之前接受MRI扫描，包括静息状态功能连接MRI（rs-fcMRI）特定序列，使用FDA批准的参数。将根据FDA批准的Neurostar方案定义每例患者的TMS给药部位，但使用无创立体定向登记系统进行记录。将使用汉密尔顿抑郁评定量表（HDRS）评估TMS治疗模式的临床抗抑郁反应。完成TMS疗程后，将根据刺激部位的功能连接性（通过rs-fcMRI表征）评价临床反应（HDRS的变化）。我们的假设是， 反应（HDRS的更大变化）将显示刺激部位和深部边缘区域（特别是膝下）之间更强的功能连接。此外，我们假设具有更好临床反应的患者将显示其实际刺激部位与我们基于连接性的靶向技术确定的“最佳”刺激部位之间更接近。如果这些假设被证明是正确的，这些结果将为TMS在抑郁症中的抗抑郁机制提供重要的见解，并为更大规模的随机临床试验提供基础，以更好地个性化定制TMS，从而提高其在患者中的抗抑郁疗效。

DESCRIPTION (provided by applicant): Transcranial magnetic stimulation (TMS) to the left dorsal-lateral prefrontal cortex (DLPFC) can be useful in the treatment of depression, and the Neuronetics(R)' Neurostar TMS protocol was approved in October of 2008 by the Food and Drug Administration for therapy of certain forms of medication-resistant depression. However, clinical responses are heterogeneous and effect size can be limited. One factor known to contribute to this response variability is differences in the specific site of stimulation in and around the DLPFC. Recent evidence from our lab suggests that the efficacy of different DLPFC targets is related to the connectivity of each target site with deeper limbic regions, specifically the subgenual cingulate. Based on these findings, we have proposed a novel connectivity-based targeting approach to identify the optimal stimulation site in individual patients to maximize antidepressant response. The goal of this project is to empirically validate this approach in actual patients undergoing TMS for depression. Patients referred for treatment by their psychiatrist and found eligible for the FDA-approved Neurostar TMS protocol will be eligible for the study. Participants will undergo an MRI scan including sequences specific to resting state functional connectivity MRI (rs-fcMRI) prior to a four week TMS treatment course (daily sessions Monday to Friday on four consecutive weeks) using FDA approved parameters. The site of TMS administration in each patient will be defined according to the FDA approved Neurostar protocol, but recorded with a noninvasive stereotactic registration system. Clinical antidepressant response to the TMS treatment paradigm will be assessed using the Hamilton Depression Rating Scale (HDRS). Upon completion of the TMS treatment course, clinical response (change in HDRS) will be evaluated as a function of the functional connectivity of the stimulation site as characterized by rs-fcMRI. Our hypothesis is that patients with better clinical response (greater change in HDRS) will show stronger functional connectivity between the stimulation site and deep limbic regions, especially the subgenual. Further, we hypothesize that patients with better clinical response will show a closer approximation between their actual stimulation site and their "optimal" stimulation site identified with our connectivity-based targeting technique. Should these hypotheses prove correct, the results would lend important insight into the antidepressant mechanism of TMS in depression and provide the foundation for a larger randomized clinical trial to better individually tailor TMS and thus improve its antidepressant efficacy across patients.