Role of functional brain connectivity on efficacy of TMS for depression

描述(申请人提供)：经颅磁刺激(TMS)左侧背侧前额叶皮质(DLPFC)可用于治疗抑郁症，Neuronetics(R)的NeuroStar TMS方案于2008年10月获得美国食品和药物管理局(FDA)的批准，用于治疗某些形式的耐药抑郁症。然而，临床反应是不同的，效果大小可能是有限的。已知的导致这种反应差异的一个因素是DLPFC内和周围刺激的特定部位的差异。我们实验室的最新证据表明，不同的DLPFC靶点的疗效与每个靶点与更深的边缘区域的连通性有关，特别是 亚属扣带。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来确定个体患者的最佳刺激部位，以最大化抗抑郁药物的反应。该项目的目标是在接受TMS治疗抑郁症的实际患者中对这种方法进行经验性验证。由他们的精神科医生推荐接受治疗的患者，如果发现符合FDA批准的NeuroStar TMS方案，将有资格参加这项研究。参与者将接受MRI扫描，包括特定于静息状态功能连接MRI(RS-fcMRI)的序列，然后使用FDA批准的参数进行四周的TMS治疗疗程(周一至周五，每天一次)。每个患者的TMS给药部位将根据FDA批准的NeuroStar方案定义，但使用非侵入性立体定向登记系统进行记录。临床抗抑郁药对TMS治疗范例的反应将使用汉密尔顿抑郁评定量表(HDRS)进行评估。在TMS疗程结束后，临床反应(HDRS的改变)将作为刺激部位功能连通性的函数进行评估，如RS-fcMRI所示。我们的假设是，临床症状较好的患者 反应(HDRS的较大变化)将显示刺激部位与边缘深部，尤其是膝下部之间的功能连接更强。此外，我们假设，临床反应较好的患者将显示出他们的实际刺激部位与我们基于连接性的靶向技术确定的“最佳”刺激部位更接近。如果这些假设被证明是正确的，结果将为TMS在抑郁症中的抗抑郁机制提供重要的洞察力，并为更大规模的随机临床试验提供基础，以便更好地个性化定制TMS，从而提高其在患者中的抗抑郁效果。

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.