Optimization of tDCS brain network engagement in depression

抑郁症中 tDCS 脑网络参与的优化

• 批准号: 10526236
• 负责人: Mayank Anant Jog
• 金额: $ 11.52万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10526236
• 关键词: Address; Anatomy; Animals; Anodes; Area; Back; Biological Models; Brain; Brain imaging; Brain region; Cathodes; Cell Culture Techniques; Characteristics; Clinical; Clinical Research; Control Groups; Data; Depressed mood; Development; Electricity; Electrodes; Engineering; Ensure; Evaluation; Experimental Designs; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Hyperactivity; Image; Interdisciplinary Study; Investigation; Investigational Therapies; Left; Location; Magnetic Resonance Imaging; Maps; Measurable; Measurement; Mental Depression; Mental disorders; Mentorship; Methodology; Methods; Mission; Modality; Modeling; National Institute of Mental Health; Neurons; Neurosciences; Outcome; Participant; Pathologic; Pathology; Patients; Performance; Phase; Play; Population; Prefrontal Cortex; Protocols documentation; Randomized; Research; Research Methodology; Research Personnel; Research Training; Rest; Role; Scalp structure; Seminal; Sensory; Short-Term Memory; Signal Transduction; Synapses; System; Techniques; Training; Work; blood oxygen level dependent; blood oxygenation level dependent response; career; clinical efficacy; clinically relevant; cognitive task; comparative; cost; depressive symptoms; design; evidence base; experimental study; follow-up; image guided; imaging approach; improved; in vivo; in vivo Model; innovation; nervous system disorder; neural circuit; neuroimaging; neuropsychiatric disorder; neuroregulation; novel; relating to nervous system; response; somatosensory

Project Summary/Abstract: Technological developments now make it possible to target specific, clinically relevant brain regions in patients using non-invasive neuromodulation. The effects of neuromodulation presumably propagate beyond the directly targeted brain regions through brain networks. To characterize this targeting of networks and thereby optimize neuromodulation, the proposed research aims to map the engagement of neural circuitry by a specific modality (transcranial direct current stimulation (tDCS)) in a specific clinical population (depression). Depression is characterized by dysfunction of the dorso-fronto-limbic network, with hypoactive left dorsolateral prefrontal cortex (DLPFC) and hyperactive right DLPFC. As investigational treatments for depression, these regions have been targeted using anodal and cathodal tDCS respectively, which are hypothesized to depolarize and hyperpolarize neurons (respectively), thereby counteracting pathological neural activity. K99 Aim 1 will use functional MRI (fMRI) during tDCS administration to investigate stimulation-specific activity and connectivity changes in the dorso-fronto-limbic network resulting from left DLPFC anodal tDCS. K99 Aim 2 will investigate whether tDCS induced activity changes are amplified in the same network when anodal left DLPFC tDCS is delivered concurrently with a salient cognitive task (2-back working memory). Work in model systems suggests that synaptic co-activation by a task during tDCS administration should enhance induced plasticity, and evidence of a super-additive two-way interaction of tDCS and task would provide presumptive evidence of target engagement to motivate future investigations of a tDCS-plus-task protocol. The R00 phase will follow up on the K99 phase's anodal tDCS research by focusing on cathodal tDCS. R00 Aim 1 will investigate stimulation-specific activity and connectivity changes in the dorso-fronto-limbic network induced by right DLPFC cathodal tDCS. R00 Aim 2 will investigate significant interactions between cathodal tDCS and the same DLPFC-coactivating cognitive task. For all aims, measurements will be carried out using a novel imaging approach employing spatially focal high- definition tDCS and concurrent blood oxygenation level dependent (BOLD) fMRI. This research is in line with the mission of NIMH/DNBBS, supporting interdisciplinary research into the modulation of clinically relevant neural circuits. My tDCS work to date has built upon my engineering background, using MRI to validate the precise delivery of tDCS in vivo. The proposed aims take the next logical step in this research, by using imaging to understand the response of brain circuits to such precisely delivered neuromodulation. To facilitate this work and help me achieve my long term goal of becoming an independent investigator in imaging-guided neuromodulation (applied to developing novel treatments for mental health disorders), training components to improve my expertise in pertinent areas of neuroscience (focusing on brain circuits and their pathology in neuropsychiatric disorders), clinical research and fMRI methodologies are proposed. The scientific aims address fundamental open questions in tDCS neuromodulation and are highly synergistic with the training objectives.

项目摘要/摘要： 现在，技术的发展使得针对患者特定的、临床相关的大脑区域成为可能 使用非侵入性神经调节。据推测，神经调节的影响可能超越了 通过大脑网络定位大脑区域。为了描述这种网络目标，从而优化 神经调节，这项拟议的研究旨在通过一种特定的模式来映射神经回路的参与 (经颅直流电刺激)在特定的临床人群(抑郁症)。忧郁症是 以背侧-额叶-边缘网络功能障碍为特征，左侧背外侧前额叶皮质活动不足 (DLPFC)和过度活跃的右DLPFC。作为抑郁症的研究治疗方法，这些区域已经被 分别使用阳极型和阴极型tDCs作为靶标，它们被假设为去极化和超极化 神经元(分别)，从而抵消病理性神经活动。K99 Aim 1将使用功能磁共振 (FMRI)，以研究刺激特异性活动和连接的变化。 左侧DLPFC节段性TDCs形成背额缘神经网络。K99 AIM 2将调查tDCS是否 当传送阳极左DLPFC tDCs时，在同一网络中放大诱发的活动变化 同时还有一项显著的认知任务(2-Back工作记忆)。在模型系统中的工作表明 在tdcs给药期间通过任务共同激活突触应增强诱导的可塑性，并且证据 TDC和TASK的超加性双向交互作用将提供目标交战的假定证据 以推动未来对tdcs+任务方案的研究。R00阶段将跟进K99阶段的 以阴极tdcs为重点的阳极tdcs研究。R00目标1将研究刺激特定活动和 右侧DLPFC阴极tdcs诱发背-额-缘网络的连通性改变。R00 Aim 2将 研究阴极tDCs和同一DLPFC-共激活认知任务之间的显著交互作用。为 所有目标、测量将使用一种新的成像方法进行，该方法采用空间聚焦高能- 定义tDCs和并发血氧水平依赖(BOLD)功能磁共振成像。这项研究与 NIMH/DNBBS的任务，支持临床相关神经调节的跨学科研究 电路。到目前为止，我的tdcs工作是建立在我的工程背景之上的，使用MRI来验证 体内递送tDCs。提议的目标在这项研究中采取了下一步合乎逻辑的步骤，通过使用成像来 了解大脑回路对这种精确传递的神经调节的反应。为了促进这项工作，并 帮助我实现我的长期目标，成为影像引导神经调节的独立研究员 (应用于开发精神健康障碍的新疗法)，培训组件以改善我的 神经科学相关领域的专业知识(侧重于神经精神病学中的脑回路及其病理学 疾病)，临床研究和fMRI方法学被提出。科学目标解决了根本问题 Tdcs神经调节方面的公开问题，并与培训目标高度协同。