Role of functional brain connectivity on efficacy of TMS for depression

功能性大脑连接对 TMS 治疗抑郁症疗效的作用

• 批准号: 8511933
• 负责人: Alvaro Pascual-Leone
• 金额: $ 23.28万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-03 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8511933
• 关键词: Accounting; Age; Anterior; Antidepressive Agents; Anxiety; Area; Behavioral; Biological Psychiatry; Brain; Brain imaging; Clinical; Country; Data; Deep Brain Stimulation; Dorsal; FDA approved; Fingers; Foundations; Frequencies; Goals; Guidelines; Hamilton Rating Scale for Depression; Hand; Hospitals; Human; Individual; Insurance; Lateral; Left; Link; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Medicare; Mental Depression; Mental disorders; Methods; Motor; Muscle; Neurologic; Neurons; Participant; Patients; Pharmaceutical Preparations; Physiologic pulse; Positioning Attribute; Prefrontal Cortex; Protocols documentation; Psychiatrist; Publishing; Randomized Clinical Trials; Recommendation; Recording of previous events; Resistance; Rest; Role; Scalp structure; Site; Staging; System; Techniques; Testing; Therapeutic; Therapeutic Intervention; Therapeutic Uses; Time; Transcranial magnetic stimulation; Treatment Protocols; United States Food and Drug Administration; Work; base; cingulate cortex; clinical effect; clinical efficacy; clinically significant; effective therapy; improved; insight; interest; nervous system disorder; novel; programs; public health relevance; response

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.

描述（由申请人提供）：对左背外侧前额叶皮层 (DLPFC) 进行经颅磁刺激 (TMS) 可用于治疗抑郁症，Neuronetics(R)' Neurostar TMS 方案于 2008 年 10 月获得批准美国食品和药物管理局用于治疗某些形式的耐药性抑郁症。然而，临床反应是异质的，效果大小可能有限。已知导致这种反应变异性的一个因素是 DLPFC 内部和周围特定刺激部位的差异。我们实验室的最新证据表明，不同 DLPFC 目标的功效与每个目标位点与更深边缘区域的连接性有关，特别是 膝下扣带回。基于这些发现，我们提出了一种新颖的基于连接的靶向方法，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。该项目的目标是在接受 TMS 治疗抑郁症的实际患者中凭经验验证这种方法。 由精神科医生转诊接受治疗并符合 FDA 批准的 Neurostar TMS 方案的患者将有资格参加该研究。参与者将接受 MRI 扫描，包括特定于静息态功能连接 MRI (rs-fcMRI) 的序列，然后使用 FDA 批准的参数进行为期 4 周的 TMS 治疗课程（连续四周周一至周五每日治疗）。每位患者的 TMS 给药部位将根据 FDA 批准的 Neurostar 方案确定，但使用无创立体定向登记系统进行记录。 TMS 治疗模式的临床抗抑郁反应将使用汉密尔顿抑郁评定量表 (HDRS) 进行评估。 TMS 治疗过程完成后，临床反应（HDRS 的变化）将根据刺激部位的功能连接进行评估，如 rs-fcMRI 所表征。我们的假设是具有更好临床表现的患者 反应（HDRS 的更大变化）将显示刺激部位和深层边缘区域（尤其是膝下区域）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表现出他们的实际刺激部位与我们基于连接的靶向技术确定的“最佳”刺激部位之间的更接近。如果这些假设被证明是正确的，那么结果将有助于深入了解 TMS 在抑郁症中的抗抑郁机制，并为更大规模的随机临床试验提供基础，以更好地个体化 TMS，从而提高其对患者的抗抑郁功效。