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.

项目摘要 重度抑郁症（MDD）的一线药物治疗仅是中等成功的。带有阳极 刺激左侧外侧前额叶皮层（DLPFC），经颅直流电流刺激（TDC），A 最小风险的低强度神经调节技术可能会引起抗抑郁作用并改善 MDD个体的认知控制。先前的证据表明，前额叶 - 束电路，包括 DLPFC和背部扣带回皮层（DACC）参与了情绪和情感的调节。 因此，它们对TDC的调节可能有助于抗抑郁作用。但是，这些程度 TDC参与了区域，其招聘如何对临床反应贡献。回复 到TDC的大小，位置和强度可能 考虑各种治疗作用。最近，已经开发了高清（HD）TDCS 更具局灶性神经刺激。在此探索性临床试验的R61阶段，我们旨在应用和 比较中至重度MDD患者的HD-TDC，常规TDC（C-TDC）和假TDCS （n = 60，n = 20）测试调节DLPFC和DACC的情绪参与的差异 使用随机的双盲设计之间的条件区域。我们将使用MRI引导的立体观念 使用并发的TDC优化和标准化DLPFC电极放置和新型MRI技术 TDCS电流在不同刺激强度下的区域分布。我们将使用3D grase pseudo- 连续的动脉自旋标记（PCASL）MRI，比较受试者在受试者完成12日30 2 Ma刺激的分钟课程，以测试TDCS与脑血流（RCBF）中与TDCS相关的变化 前额叶电路。显着的TDC诱导DLPFC的磁场变化和RCBF的显着变化 在DLPFC和DACC中的基线和TDC试验的末尾之间的任何一个主动TDC 与假相比的条件将构成进入R33阶段的GO-NO-GO标准。使用 活跃的TDC模式显示出更大的目标参与和神经生理效应而没有周围 副作用，R33阶段将随机将中度至重度MDD的患者随机（n = 100，n = 50 组）为活动或假手术留下阳极DLPFC TDC。患者将再次完成包括TDCS-的MRI扫描 当前的映射和PCASL以及两个探索认知控制和情感的功能成像任务 消极偏见，在完成为期12天的30分钟试验之前和之后，招募前额叶夹具电路 TDCS会议。证明目标与主动TDCS的目标参与与改进的相关性不同 情绪（主要结果），认知功能和与任务相关的大脑激活的变化（次要结果） 将构成继续R01调查的标准。预计该试验的结果将导致 优化MRI指导的TDC治疗MDD，并加深对生理机制的理解 TDCS治疗。

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