Optimization of tDCS brain network engagement in depression

抑郁症中 tDCS 脑网络参与的优化

• 批准号: 10704618
• 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/10704618
• 关键词: Acceleration; Address; Anatomy; Animals; Anodes; Area; Back; Biological Models; Brain; Brain imaging; Brain region; Cell Culture Techniques; Clinical; Clinical Research; Control Groups; Data; Depressed mood; 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; 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; follow-up; image guided; imaging approach; improved; in vivo; in vivo Model; innovation; nervous system disorder; neural; neural circuit; neuroimaging; neuropsychiatric disorder; neuroregulation; novel; response; somatosensory; technology development; transcranial direct current stimulation

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： 现在的技术发展使得针对患者的特定临床相关大脑区域成为可能 使用非侵入性神经调节。神经调节的作用大概可以直接传播 通过大脑网络靶向大脑区域。表征网络的目标，从而优化 神经调节，拟议的研究旨在通过特定方式绘制神经回路的参与 （抑郁症）（抑郁症）中（经颅直流刺激（TDC））。抑郁是 具有多功能 - 纤维膜网络功能障碍的特征，具有左侧外侧前额叶皮层的功能障碍 （DLPFC）和多动右DLPFC。作为抑郁症的研究治疗，这些地区已经 分别使用阳极和阴极TDC靶向，这些TDC被认为是去极化和超极化的 分别（分别是神经元），从而抵消病理神经活动。 K99 AIM 1将使用功能性MRI （fMRI）在TDCS给药期间，研究刺激特异性活性和连通性的变化 左DLPFC阳极TDC产生的dorso-fronto-limbic网络。 K99 AIM 2将调查TDC是否 当阳极左DLPFC TDCS交付时，诱导的活动变化在同一网络中扩增 同时与一个显着的认知任务（2退工作记忆）。模型系统中的工作表明 TDCS给药期间任务通过任务的突触共同激活应增强诱导的可塑性，并证明 TDC和任务的超级加性双向互动将提供目标参与的推定证据 激励未来对TDCS-Plus任务协议的研究。 R00阶段将在K99阶段进行跟进 阳极TDCS研究通过关注阴极TDC。 R00 AIM 1将研究特定刺激的活性和 右DLPFC阴极TDC诱导的Dorso-fronto-limbic网络的连通性变化。 R00 AIM 2将 研究阴极TDC与相同的DLPFC调整认知任务之间的显着相互作用。为了 所有目的，测量将使用新型成像方法进行，采用空间局灶性高 - 定义TDC和并发的血液氧合水平取决于（BOLD）fMRI。这项研究符合 NIMH/DNBB的使命，支持跨学科研究，以调节临床相关的神经 电路。迄今为止，我的TDC在我的工程背景上建立了工作，使用MRI来验证确切的 在体内递送TDC。提出的目标是在这项研究中采取下一个逻辑步骤，将成像用于 了解大脑回路对这种精确递送的神经调节的反应。促进这项工作和 帮助我实现成为成像引导神经调节的独立研究者的长期目标 （适用于开发精神疾病的新型治疗方法），培训组件以改善我的 神经科学领域的专业知识（专注于脑电路及其病理学的神经精神病学 疾病），提出了临床研究和fMRI方法。科学目的解决基本 在TDCS神经调节中的开放问题，与培训目标高度协同。