Optimization of tDCS brain network engagement in depression

抑郁症中 tDCS 脑网络参与的优化

基本信息

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
项目类别：
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

项目摘要

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。神经调节的影响可能会传播到直接的范围之外通过大脑网络瞄准大脑区域。表征网络的目标并从而优化神经调节，拟议的研究旨在通过特定方式绘制神经回路的参与（经颅直流电刺激（tDCS））在特定临床人群（抑郁症）中的应用。抑郁症是其特征是背侧-额叶-边缘网络功能障碍，左背外侧前额叶皮质功能减退（DLPFC）和过度活跃的右侧 DLPFC。作为抑郁症的研究性治疗方法，这些区域已被分别使用阳极和阴极 tDCS 进行靶向，假设可以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 将使用功能性 MRI (fMRI) 在 tDCS 管理期间研究刺激特异性活动和连接变化背额-额叶-边缘网络由左 DLPFC 阳极 tDCS 产生。 K99 Aim 2 将调查 tDCS 是否当阳极左侧 DLPFC tDCS 被传递时，诱导的活动变化在同一网络中被放大同时进行显着的认知任务（2-back工作记忆）。模型系统中的工作表明 tDCS 管理过程中一项任务的突触共激活应该会增强诱导的可塑性，并且有证据表明 tDCS 和任务的超加性双向交互将提供目标参与的推定证据激发未来对 tDCS 加任务协议的研究。 R00阶段将跟进K99阶段阳极 tDCS 研究重点关注阴极 tDCS。 R00 目标 1 将调查刺激特异性活动和由右侧 DLPFC 阴极 tDCS 引起的背额-额叶-边缘网络的连接变化。 R00 目标 2 将研究阴极 tDCS 和相同的 DLPFC 共激活认知任务之间的显着相互作用。为了所有目标，测量将使用一种新颖的成像方法进行，该方法采用空间聚焦高定义 tDCS 和并发血氧水平依赖 (BOLD) fMRI。这项研究符合 NIMH/DNBBS 的使命是支持临床相关神经调节的跨学科研究电路。迄今为止，我的 tDCS 工作建立在我的工程背景之上，使用 MRI 来验证精确的体内 tDCS 的传递。所提出的目标在本研究中采取了下一个合乎逻辑的步骤，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成为成像引导神经调节领域的独立研究者的长期目标（应用于开发治疗精神健康障碍的新疗法），培训内容以改善我的神经科学相关领域的专业知识（重点关注神经精神病学中的脑回路及其病理学）疾病），提出了临床研究和功能磁共振成像方法。科学目标解决基本问题经颅直流电刺激 (tDCS) 神经调节中的开放性问题与培训目标高度协同。