Neural Target Identification for Functional Disability Associated with Alcohol Related Characteristics Among Veterans with Co-occurring Alcohol Use Disorder and Traumatic Brain Injury

患有同时发生的酒精使用障碍和创伤性脑损伤的退伍军人中与酒精相关特征相关的功能障碍的神经目标识别

• 批准号: 10701806
• 负责人: Amy Herrold
• 金额: --
• 依托单位: EDWARD HINES JR VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10701806
• 关键词: Accounting; Activities of Daily Living; Address; Alcohol consumption; Alcohol dependence; Alcohols; Brain; Caring; Characteristics; Classification; Clinical; Data; Devices; FDA approved; Factor Analysis; Fiber; Frequencies; Functional Magnetic Resonance Imaging; Goals; Health; Health Status; Healthcare; Image; Intervention; Interview; Investments; Knowledge; Left; Literature; MRI Scans; Measures; Mental Depression; Mental Health; Mission; Neuropsychology; Outcome; Outcomes Research; Participant; Patient Self-Report; Prefrontal Cortex; Procedures; Process; Protocols documentation; Randomized; Recording of previous events; Recovery; Recovery of Function; Rehabilitation therapy; Research; Rest; Sampling; Severities; Site; Societies; Structure; Symptoms; Testing; Therapeutic; Translating; Traumatic Brain Injury; Veterans; World Health Organization Disability Assessment Schedule; alcohol abuse therapy; alcohol craving; alcohol cue; alcohol use disorder; brain dysfunction; density; design; effective therapy; efficacy testing; follow-up; functional disability; gray matter; improved; indexing; innovation; mild traumatic brain injury; military veteran; multimodal neuroimaging; multimodality; neural; neuroimaging; neurological rehabilitation; neuropsychiatry; neuroregulation; recruit; rehabilitation research; repetitive transcranial magnetic stimulation; response; social; substance use; white matter

Alcohol use disorder (AUD) and mild traumatic brain injury (mTBI) impact functional abilities. AUD occurs in up to 35% of Veterans with mTBI. Evidence suggests that co-occurrence of AUD and mTBI (AUD+mTBI) leads to an exacerbation of brain dysfunction, symptom manifestation, and ultimately, functional disability. Alcohol- related characteristics are operationally defined per AUD symptoms and outcomes including, but not limited to, alcohol consumption, alcohol craving, and AUD severity. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulatory treatment that will soon be a treatment option at 30 VAs nationwide. Preliminary rTMS efficacy is demonstrated for AUD alone and mTBI alone using a variety of neural targets. rTMS is, thus, a promising treatment for AUD+mTBI. The objectives of this study are to 1) identify neural targets (i.e. site of stimulation) associated with both alcohol-related characteristics and self-reported functional disability, and 2) assess preliminary efficacy and sustainability of a high frequency rTMS protocol applied to these customized neural targets relative to the commonly used left dorsolateral prefrontal cortex (DLPFC) site. Addressing these objectives are essential steps towards our long-term research goal [to customize and clinically implement a rTMS treatment] that can improve brain function resulting in optimal recovery for Veterans with AUD+mTBI. To address the first study objective, Veterans will be recruited and classified into one of two groups based on structured-interviews, self-report measures, and neuropsychological assessments: 1) AUD+mTBI, and 2) [Veteran controls] without a history or symptoms of mTBI or AUD. Alcohol-related characteristics will be assessed through objective measures of alcohol use, self-report measures, and structured interviews. Self-reported functional disability will be assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS). Neuroimaging metrics will be assessed through a multi- modal, functional and structural Magnetic Resonance Imaging (MRI) scan. Participants will complete a functional MRI (fMRI) protocol where brain activation will be measured in response to viewing images related to alcohol, compared to neutral images. Advanced neuroimaging procedures to determine the structural integrity of white matter fibers in the brain and spontaneous activity in brain networks, a process called resting state functional connectivity (rsFC), will also be conducted. To address the second study objective, AUD+mTBI Veterans will receive rTMS at one site randomly assigned from a set of 4 sites: 3 customized neural targets identified in this study, and the commonly used left DLPFC. AUD+mTBI Veterans will complete 10 PLACEBO, then 10 ACTIVE rTMS sessions in a within-subjects design. Follow-up WHODAS assessments will occur at 2- weeks, 1-month and 6-months post-ACTIVE rTMS. Aim 1 will identify unique neural targets for rTMS to treat AUD+mTBI by determining which multi-modal neuroimaging metrics are most strongly associated with both alcohol-related characteristics and functional disability. Aim 2 will [test preliminary efficacy of high-frequency rTMS administered over the customized neural targets] to treat functional disability among Veterans with AUD+mTBI. Aim 3 will assess sustainability of rTMS effects on functional disability for Veterans with AUD+mTBI. We hypothesize that for Veterans with AUD+mTBI, there are neural substrates of AUD related to functional disability, and that neuromodulation of these substrates will be related to gains in functional disability. Our innovative approach represents an advancement in the field of neurorehabilitation because a neural target will be systematically defined, using multi-modal neuroimaging, prior to preliminary rTMS efficacy and sustainability testing. These steps are necessary to customize rTMS treatment for a population of Veterans with co-occurring conditions and unique health care needs. Thus, the outcomes of this research will optimize function for Veterans with AUD+mTBI.

酒精使用障碍 (AUD) 和轻度创伤性脑损伤 (mTBI) 会影响功能能力。澳元出现在 35% 的退伍军人患有 mTBI。有证据表明 AUD 和 mTBI (AUD+mTBI) 同时出现会导致 脑功能障碍、症状表现以及最终功能障碍的加剧。酒精- 相关特征根据 AUD 症状和结果进行操作定义，包括但不限于： 饮酒量、对酒精的渴望以及澳元的严重程度。重复经颅磁刺激（rTMS）是 一种非侵入性神经调节治疗，很快将成为全国 30 个 VA 的治疗选择。 使用各种神经靶点证明了单独使用 AUD 和单独使用 mTBI 时的初步 rTMS 功效。 因此，rTMS 是 AUD+mTBI 的一种有前途的治疗方法。本研究的目标是 1) 识别神经元 与酒精相关特征和自我报告的功能相关的目标（即刺激部位） 残疾，以及 2) 评估应用于高频 rTMS 协议的初步功效和可持续性 这些定制的神经目标相对于常用的左背外侧前额叶皮层 (DLPFC) 部位。 实现这些目标是实现我们长期研究目标[定制和 临床实施 rTMS 治疗]，可以改善大脑功能，从而实现最佳康复 患有 AUD+mTBI 的退伍军人。为了实现第一个研究目标，将招募退伍军人并将其分类为 基于结构化访谈、自我报告测量和神经心理学评估的两组之一： 1) AUD+mTBI，以及 2) [退伍军人对照] 无 mTBI 或 AUD 病史或症状。酒精相关 将通过酒精使用的客观测量、自我报告测量和 结构化面试。自我报告的功能障碍将使用世界卫生组织进行评估 残疾评估表 2.0 (WHODAS)。神经影像指标将通过多方面评估 模态、功能和结构磁共振成像 (MRI) 扫描。参与者将完成一个 功能性 MRI (fMRI) 协议，其中将根据观看相关图像来测量大脑激活 与中性图像相比，酒精。先进的神经影像程序来确定结构 大脑中白质纤维的完整性和大脑网络中的自发活动，这一过程称为静息 状态功能连接（rsFC）也将进行。为了实现第二个研究目标，AUD+mTBI 退伍军人将在从一组 4 个站点中随机分配的一个站点接受 rTMS：3 个定制的神经目标 本研究中确定了常用的左 DLPFC。 AUD+mTBI 退伍军人将完成 10 PLACEBO， 然后在受试者内设计中进行 10 次主动 rTMS 会话。后续 WHODAS 评估将于 2 点进行 激活 rTMS 后几周、1 个月和 6 个月。目标 1 将确定 rTMS 治疗的独特神经靶点 AUD+mTBI，通过确定哪些多模态神经影像指标与两者最密切相关 酒精相关特征和功能障碍。目标2将[测试高频的初步功效 rTMS 对定制的神经目标进行管理]以治疗患有以下疾病的退伍军人的功能障碍 澳元+mTBI。目标 3 将评估 rTMS 对患有以下疾病的退伍军人功能残疾的影响的可持续性 澳元+mTBI。我们假设对于患有 AUD+mTBI 的退伍军人来说，AUD 的神经基质与 功能障碍，并且这些底物的神经调节将与功能的增强有关 残疾。我们的创新方法代表了神经康复领域的进步，因为 在初步 rTMS 疗效之前，将使用多模式神经影像系统地定义神经目标 和可持续性测试。这些步骤对于为以下人群定制 rTMS 治疗是必要的： 患有并发疾病和独特医疗保健需求的退伍军人。因此，本研究的结果将 使用 AUD+mTBI 优化退伍军人功能。