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: 10264824
• 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 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10264824
• 关键词: Accounting; Activities of Daily Living; Address; Alcohol consumption; Alcohol dependence; Alcohols; Brain; Brain Injuries; Characteristics; Clinical; Custom; Data; Devices; FDA approved; Factor Analysis; Fiber; Frequencies; Functional Magnetic Resonance Imaging; Goals; Health Status; Healthcare; Image; Intervention; Interview; Knowledge; Left; Literature; MRI Scans; Measures; 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; TBI treatment; Testing; Therapeutic; Time; Translating; Traumatic Brain Injury; Veterans; World Health Organization Disability Assessment Schedule; alcohol abuse therapy; alcohol craving; alcohol cue; alcohol use disorder; base; brain dysfunction; density; design; effective therapy; efficacy testing; follow-up; functional disability; gray matter; improved; indexing; innovation; mild traumatic brain injury; military veteran; multimodality; nerve injury; neuroimaging; neurological rehabilitation; neuropsychiatry; neuroregulation; recruit; rehabilitation research; relating to nervous system; repetitive transcranial magnetic stimulation; response; social; substance use; treatment effect; 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）影响功能能力。 AUD发生在UP中 有35％的退伍军人有MTBI。有证据表明AUD和MTBI（AUD+MTBI）的共同发生导致 大脑功能障碍，症状表现以及最终功能障碍的加剧。酒精- 相关特征是每个AUD症状和结果的操作定义，包括但不限于 饮酒，渴望和声音严重程度。重复的经颅磁刺激（RTMS）为 一种非侵入性神经调节治疗，很快将成为全国30 VAS的治疗选择。 使用各种神经靶标证明了单独使用AUD和MTBI的初步RTMS功效。 因此，RTMS是AUD+MTBI的有前途的治疗方法。这项研究的目标是1）确定神经 与酒精相关特征和自我报告的功能相关的靶标（即刺激部位） 残疾和2）评估适用于 这些定制的神经靶标相对于常用的左侧外侧前额叶皮层（DLPFC）部位。 解决这些目标是朝着我们长期研究目标（自定义和 临床实施RTMS治疗]，可以改善大脑功能，从而最佳恢复 带有aud+mtbi的退伍军人。为了满足第一个研究目标，将招募退伍军人并将其分类为 基于结构化探视，自我报告措施和神经心理学评估的两个组之一： 1）aud+mtbi和2）[退伍军人对照]没有病史或MTBI或AUD症状。酒精相关 特征将通过客观的饮酒，自我报告措施和 结构化访谈。自我报告的功能残疾将使用世界卫生组织评估 残疾评估附表2.0（WHODAS）。神经影像学指标将通过多种 模态，功能和结构磁共振成像（MRI）扫描。参与者将完成 功能性MRI（fMRI）方案，其中将根据查看图像相关的图像来测量大脑激活 与中性图像相比，酒精。高级神经影像学程序，以确定结构 大脑中白质纤维的完整性和大脑网络中自发活动的完整性，这一过程称为静止 状态功能连接（RSFC）也将进行。为了解决第二个研究目标，AUD+mtbi 退伍军人将在从一组4个站点随机分配的一个站点上接收RTM：3个自定义神经目标 在这项研究中确定，并且常用的左DLPFC。 AUD+MTBI退伍军人将完成10个安慰剂， 然后在受试者内设计中10个活动RTMS会话。随访将在2-中进行WHODAS评估 几周，1个月和6个月的活性RTMS。 AIM 1将确定RTM的独特神经目标 AUD+MTBI通过确定哪种多模式神经影像学指标与两者最密切相关 与酒精有关的特征和功能障碍。 AIM 2将[测试高频的初步功效 对自定义神经靶标的管理的RTMS]，以治疗具有 aud+mtbi。 AIM 3将评估RTMS的可持续性对退伍军人的功能残疾的影响 aud+mtbi。我们假设对于具有aud+mtbi的退伍军人，有与 功能障碍，这些底物的神经调节将与功能的提高有关 残疾。我们的创新方法代表了神经康复领域的进步，因为 在初步的RTMS功效之前，将使用多模式神经影像系统地定义神经靶标 和可持续性测试。这些步骤对于自定义RTMS治疗是必要的 具有同时发生条件和独特医疗保健需求的退伍军人。因此，这项研究的结果将 优化具有AUD+MTBI的退伍军人的功能。