Assessing an electroencephalography (EEG) biomarker of response to transcranial magnetic stimulation for major depression

评估重度抑郁症对经颅磁刺激反应的脑电图 (EEG) 生物标志物

• 批准号: 9933192
• 负责人: Amit Etkin
• 金额: --
• 依托单位: WHITE RIVER JUNCTION VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9933192
• 关键词: Antidepressive Agents; Antidepressive Agents; Area; Area; Biological Markers; Biological Markers; Brain; Brain; Brain region; Brain region; Clinical; Clinical; Data Set; Deep Brain Stimulation; Deep Brain Stimulation; Devices; Devices; Disease remission; Disease remission; Electroencephalography; Electroencephalography; Electromagnetics; Electromagnetics; Enrollment; Enrollment; Future; Future; Goals; Goals; Grant; Grant; Infrastructure; Infrastructure; Intervention; Intervention; Left; Left; Machine Learning; Machine Learning; Major Depressive Disorder; Major Depressive Disorder; Measures; Measures; Mental Depression; Mental Depression; Methods; Methods; Patients; Patients; Pattern; Pattern; Pharmaceutical Preparations; Pharmaceutical Preparations; Post-Traumatic Stress Disorders; Post-Traumatic Stress Disorders; Prefrontal Cortex; Prefrontal Cortex; Psychotherapy; Psychotherapy; ROC Curve; ROC Curve; Research; Research; Research Infrastructure; Research Infrastructure; Research Personnel; Research Personnel; Rest; Rest; Sampling; Sampling; Severities; Severities; Site; Site; Testing; Testing; Time; Time; Transcranial magnetic stimulation; Transcranial magnetic stimulation; Veterans; Veterans; Work; Work; base; base; brain electrical activity; brain electrical activity; cost; cost; disability; disability; effective therapy; effective therapy; evidence base; evidence base; expectation; expectation; functional restoration; functional restoration; infrastructure development; infrastructure development; inventory of depressive symptomatology; inventory of depressive symptomatology; large datasets; mood regulation; mood regulation; mortality; mortality; network dysfunction; network dysfunction; neural circuit; neural circuit; neural network; neural network; novel; novel; novel strategies; novel strategies; personalized medicine; personalized medicine; potential biomarker; potential biomarker; predicting response; predicting response; predictive marker; predictive marker; programs; programs; response; response; response biomarker; response biomarker; therapy development; therapy development; treatment planning; treatment planning; treatment response; treatment response; treatment-resistant depression; treatment-resistant depression

Major Depressive Disorder (MDD) is highly prevalent among Veterans and associated with significant cost, disability and mortality. Although evidence-based medications and psychotherapies are available to treat MDD, full and sustained remission is uncommon. Transcranial magnetic stimulation (TMS) is an FDA-cleared intervention that offers a novel strategy for treating patients with treatment-resistant depression (TRD). TMS is available within the VA through the VA Clinical TMS Pilot Program. TMS is based in a neural circuit paradigm of MDD positing that stimulation at a key node (e.g., dorsolateral prefrontal cortex) can restore function within a network of brain regions involved in mood regulation. Although a substantial number of TRD patients respond well to TMS, many do not. This suggests some patients have a form of neural network dysfunction that is more amenable to TMS. Resting electroencephalography (EEG) provides a safe, convenient and reliable way to measure focal brain electrical activity and neural network function. Prior studies have identified EEG markers associated with response to antidepressant medications, but limited research has been conducted to identify EEG markers predictive of an antidepressant response with TMS. This is a critical gap, since TMS likely operates via direct modulation of neural network activity, such that baseline differences in neural network function should help identify which patients are more or less likely to respond to TMS. Investigators in our group have identified putative predictive EEG-based biomarkers for response to TMS for TRD. One of these (differential patterns of gamma oscillations) may specifically predict response to 10 Hz TMS applied to the left dorsolateral prefrontal cortex, the type of TMS received by >80% of Veterans receiving TMS in the TMS Pilot Program. Another (changes in theta cordance early in the course of treatment) may predict eventual response to TMS; this potential biomarker was identified by Dr. Andrew Leuchter (a consultant on this grant) and has been shown to also predict response to antidepressant medications and deep brain stimulation for TRD. By adding baseline (pretreatment) and weekly resting EEG assessment to the VA National Clinical TMS Pilot Program, the goals of this study are to: (1) test a potential response biomarker measured at baseline in a large sample of Veterans receiving TMS to treat depression (N=400); (2) assess whether a second putative biomarker (early changes in theta cordance during treatment) predict eventual response to TMS; (3) leverage this large sample to identify other potential biomarkers (such as markers of early versus late response to TMS, markers of response to other TMS parameters (e.g., 5 Hz, 1 Hz or theta burst TMS), and markers of change with treatment that may speak to mechanism); and (3) create an infrastructure to rapidly identify and test additional EEG-based biomarkers of treatment response in patients with depression and other psychiatric conditions relevant to the VA, such as PTSD and/or TBI. The infrastructure created will initially consist of the five sites that form the core of this study group, then expand to include a total of 10 sites over the course of the project. It is hoped that this infrastructure will continue to expand over time to include as many of the sites in the TMS Pilot Program as possible. This study, and the infrastructure created, will be of high value to Veterans by taking an important step towards a personalized medicine approach to the use of TMS for TRD.

重度抑郁症（MDD）在退伍军人中非常普遍，并且与巨大的成本相关，