Imaging-guided tDCS therapy in major depression

影像引导 tDCS 治疗重度抑郁症

• 批准号: 10450188
• 负责人: Katherine L Narr
• 金额: $ 104.18万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10450188
• 关键词: 3-Dimensional; Acute; Anatomy; Anodes; Anterior; Antidepressive Agents; Behavior; Biophysics; Brain; Cerebrovascular Circulation; Clinical; Clinical Trials; Cognitive; Core-Binding Factor; Depressed mood; Disease; Dorsal; Double-Blind Method; Economics; Electroconvulsive Therapy; Electrodes; Emotions; Event; Functional Imaging; Future; Goals; Individual; Intervention; Investigation; Lead; Left; Link; Location; MRI Scans; Magnetic Resonance Imaging; Major Depressive Disorder; Maps; Measures; Mediating; Mental Depression; Metabolism; Methods; Modality; Moods; Neuronavigation; Outcome; Outcomes Research; Patients; Pattern; Perfusion; Peripheral; Pharmacotherapy; Phase; Physiological; Physiology; Placebo Effect; Prefrontal Cortex; Protocols documentation; Randomized; Research; Signal Transduction; Standardization; Techniques; Testing; Theoretical model; Therapeutic Effect; Time; Variant; antidepressant effect; arterial spin labeling; base; behavior measurement; behavior test; cingulate cortex; cognitive change; cognitive control; cognitive function; cohort; depressed patient; depressive symptoms; design; image guided; improved; improved outcome; in vivo; individual variation; innovation; magnetic field; minimal risk; mood regulation; neural circuit; neural stimulation; neurophysiology; neuroregulation; noninvasive brain stimulation; novel; personalized medicine; primary outcome; public health relevance; recruit; relating to nervous system; response; secondary outcome; side effect; symptomatic improvement; treatment trial; trial comparing

PROJECT SUMMARY First-line pharmacotherapies for major depressive disorder (MDD) are only moderately successful. With anodal stimulation of the left dorsolateral prefrontal cortex (DLPFC), transcranial direct current stimulation (tDCS), a low-intensity neuromodulation technique of minimal risk, may elicit antidepressant effects and improve cognitive control in individuals with MDD. Prior evidence suggests that prefrontal-limbic circuits, including the DLPFC and dorsomedial anterior cingulate cortex (dACC), are involved in the regulation of mood and emotion. Their modulation by tDCS may thus contribute to antidepressant effects. However, the extent to which these regions are engaged by tDCS and how their recruitment contributes to clinical response is unknown. Response to tDCS also remains mixed at the individual level where the size, location and intensity of stimulation might account for varied therapeutic effects. Recently, high definition (HD) tDCS has been developed that allows for more focal neural stimulation. During the R61 phase of this Exploratory Clinical Trial we aim to apply and compare HD-tDCS, conventional tDCS (C-tDCS) and sham tDCS in patients with moderate to severe MDD (N=60, n=20 in each group) to test for differences in the engagement of mood regulating DLPFC and dACC regions between conditions using a randomized, double blind design. We will use MRI-guided stereotaxy to optimize and standardize DLPFC electrode placement and novel MRI techniques with concurrent tDCS to test the regional distribution of tDCS current at different stimulation intensities. We will use 3D GRASE pseudo- continuous arterial spin labeling (pCASL) MRI, compared before and after subjects complete 12 daily 30 minute sessions of 2 mA stimulation, to test for tDCS-related changes in regional cerebral blood flow (rCBF) in prefrontal circuitry. Significant tDCS induced magnetic field changes in DLPFC and significant changes in rCBF between baseline and the end of the tDCS trial in the DLPFC and dACC for either of the active tDCS conditions compared to sham will constitute the go-no-go criterion for proceeding to the R33 Phase. Using the active tDCS modality showing greater target engagement and neurophysiological effects without peripheral side effects, the R33 Phase will randomize patients with moderate to severe MDD (N=100, n=50 in each group) to active or sham left anodal DLPFC tDCS. Patients will again complete MRI scans including tDCS- current mapping and pCASL as well as two functional imaging tasks probing cognitive control and emotion negativity bias, recruiting prefrontal-limbic circuitry, before and after completing a 12-day trial of 30-minute tDCS sessions. Demonstration that target engagement with active tDCS varies in association with improved mood (primary outcome), cognitive function and changes in task-related brain activation (secondary outcomes) will constitute the criterion for continued R01 investigation. Results of this trial are expected to lead to an optimized MRI guided tDCS treatment of MDD and deepen understanding of the physiological mechanisms of tDCS therapy.

项目总结 治疗重度抑郁障碍(MDD)的一线药物治疗只取得了一定的成功。带阳极 刺激左侧背外侧前额叶皮质(DLPFC)、经颅直流电刺激(TDC)、 风险最小的低强度神经调节技术，可能会产生抗抑郁作用并改善 MDD患者的认知控制。先前的证据表明，前额叶-边缘环路，包括 DLPFC和背内侧前扣带回参与情绪和情绪的调节。 因此，tDCs对它们的调节可能有助于抗抑郁作用。然而，在很大程度上这些 TDC参与了各地区的工作，他们的招募如何有助于临床反应尚不清楚。响应 TDCs在个体水平上也是混合的，刺激的大小、位置和强度可能 说明不同的治疗效果。最近，已经开发出高清晰度(HD)tdcs，其允许 更多的局部神经刺激。在这项探索性临床试验的R61阶段，我们的目标是应用和 中重度MDD患者HD-tDCs、常规tDCs(C-tDCs)和Sham tDCs的比较 (每组n=60，n=20)以检验情绪调节DLPFC和DACC的参与程度的差异 条件之间的区域使用随机、双盲设计。我们将使用MRI引导的立体定向术 优化和标准化DLPFC电极放置和新的MRI技术，并使用并发tDCS进行测试 不同刺激强度下tdcs电流的区域分布。我们将使用3D Grase伪 连续动脉自旋标记(PCASL)磁共振成像，比较受试者完成12天30天前后的情况 2 mA刺激分钟，以测试tdcs相关局部脑血流量(RCBF)的变化。 前额叶回路。TDCS引起的DLPFC磁场显著变化和rCBF显著变化 在DLPFC和DACC中的两个激活的tDC中的tDCS试验的基线和结束之间 与Sham相比的条件将构成进入R33阶段的进行-不进行的标准。使用 主动TDC模式显示出更大的靶点参与和神经生理效应，而不需要外周 副作用，R33期将中重度MDD患者随机分组(N=100，n=50) 组)激活或假左侧阳极DLPFC tDCs。患者将再次完成包括tDCs在内的MRI扫描- 当前的标测和pCASL以及两个探测认知控制和情绪的功能成像任务 负性偏向，招募前额叶边缘回路，在完成为期12天的30分钟试验前后 Tdcs会话。演示与主动tDC的目标接洽随改进而变化 情绪(主要结果)、认知功能和任务相关脑激活的变化(次要结果) 将构成继续调查R01的标准。这项试验的结果预计将导致 优化MRI引导下经颅多普勒超声治疗MDD，加深对MDD生理机制的认识 Tdcs疗法。

项目成果

In-vivo imaging of targeting and modulation of depression-relevant circuitry by transcranial direct current stimulation: a randomized clinical trial.

• DOI: 10.1038/s41398-021-01264-3
• 发表时间: 2021-02-24
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Jog MS;Kim E;Anderson C;Kubicki A;Kayathi R;Jann K;Yan L;Leaver A;Hellemann G;Iacoboni M;Woods RP;Wang DJJ;Narr KL
• 通讯作者: Narr KL

Transcranial direct current stimulation (tDCS) in depression induces structural plasticity.

• DOI: 10.1038/s41598-023-29792-6
• 发表时间: 2023-02-17
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Jog, Mayank A.;Anderson, Cole;Kubicki, Antoni;Boucher, Michael;Leaver, Amber;Hellemann, Gerhard;Iacoboni, Marco;Woods, Roger;Narr, Katherine
• 通讯作者: Narr, Katherine