Evaluating Neural Architecture as a Novel Biomarker for TMS Efficacy in AUD

项目摘要 酒精使用障碍(AUD)目前被定位为可预防死亡的第三大原因 美国，每年造成88,000人死亡。2019年，与以下项目相关的医疗保健总费用 澳元超过2,240亿美元。AUD的治疗努力中的一个共同目标是防止再次饮酒。 虽然有几种药物疗法可用，但这些疗法的依从性很低，而且 大约60%从事这种行为的人在6个月内复发。此外，这些治疗方法 以一种相对全球化的方式调节大脑。来自AUD患者的神经成像研究的证据表明 前额纹状体神经回路表现出对酒精信号的反应活性升高，这可能随后 预测复发。因此，人们对开发新的、神经回路特异的治疗方法产生了兴趣。 改善AUD治疗结果的工具。经颅磁刺激(TMS)就是这样一种非 侵入性的神经电路专用工具。通过电磁感应，可以施加TMS的重复脉冲 以改变刺激部位的神经活动，并可以沿着完整的白质束传播到 改变下游连接的神经活动，如纹状体。然而，众所周知，个人 AUD患者的灰质体积普遍减少(影响刺激部位)以及 白质完整性降低(影响MPFC和纹状体之间的束)。的主要目标是 这项F31研究建议是为了确定灰质体积对MPFC的影响(目标1)和 MPFC和纹状体之间的白质完整性(目标2)关于MPFC与TMS相关的变化- 纹状体活动对酒精暗示的反应。此外，该提案计划将AIMS 1和2与临床相结合 AUD的生物标志物，如性别和饮酒严重程度，以评估这些因素的相对贡献 在TMS中，酒精诱导的MPFC-纹状体活动的相关变化。这一建议还得到了一次培训的支持 该计划包括4个领域：神经影像分析、科学交流、AUD的临床前景以及 多元统计。这项为期2年的F31奖学金将通过利用我们的现有数据集进行分析 实验室。这项F31提案的母公司临床试验招募了50名患有AUD的寻求治疗的患者，以 在基线时接受MRI扫描，然后进行10天的真实或假TMS，然后在治疗后进行MRI扫描， 治疗后1个月，治疗后2个月。每一次核磁共振扫描都包括一个高分辨率的解剖 图像(AIM 1)、弥散峰度成像(AIM 2)和测量酒精线索诱导的功能磁共振任务 MPFC-纹状体回路中的功能连接。将使用尖端方法来分析数据 包括：基于体素的形态测量、电场建模、扩散峰度 成像、功能连通性分析和多变量统计。候选人将纳入指导意见 来自神经成像和澳大利亚大学的专家(Hanlon和Jensen博士)对这些目标进行评估。

Project Summary Alcohol Use Disorders (AUDs) are currently positioned as the 3rd leading cause of preventable death in the United States, contributing to 88,000 deaths per year. In 2019, total allied costs of medical care associated with AUD exceeded $224 billion. A common goal among treatment efforts in AUD is to prevent relapse to drinking. Although several pharmacological treatments are available, adherence to these treatments is low and approximately 60% of individuals who engage in them relapse within 6 months. Further, these treatments modulate the brain in a relatively global fashion. Evidence from neuroimaging studies of AUD patients has shown that fronto-striatal neural-circuitry shows elevated activity in response to alcohol cues which may subsequently predict relapse. Thus, there is an emerging interest in developing novel, neural-circuit specific therapeutic tools to enhance AUD treatment outcomes. Transcranial magnetic stimulation (TMS) is one such non- invasive, neural-circuit specific tool. Through electromagnetic induction, repetitive pulses of TMS can be applied to the MPFC to change neural activity at the site of stimulation and can travel along intact white matter tracts to change neural activity in downstream connections such as the striatum. However, it is well known that individuals with AUD suffer from widespread reductions in gray matter volume (impacting the site of stimulation) as well as reductions in white matter integrity (impacting the tract between the MPFC and striatum). The primary goal of this F31 research proposal is to determine the influence of gray matter volume in the MPFC (Aim 1) and white matter integrity between the MPFC and striatum (Aim 2) on TMS associated change in MPFC- striatal activity in response to alcohol cues. Further, this proposal plans to integrate Aims 1 & 2 with clinical biomarkers for AUD such as gender and drinking severity to evaluate the relative contributions of these factors in TMS related change in alcohol cue-induced MPFC-striatal activity. This proposal is complimented by a training plan that includes 4 domains: neuroimaging analysis, scientific communication, clinical perspective of AUD, and multivariate statistics. This 2-year F31 fellowship will be analyzed by leveraging an existing data set from our laboratory. The parent clinical trial for this F31 proposal recruited 50 treatment-seeking individuals with AUD to receive MRI scans at baseline, followed by 10 days of real or sham TMS, followed by MRI scans after treatment, 1 month after treatment, and 2 months after treatment. Each MRI scan consisted of a high-resolution anatomical image (Aim 1), diffusion kurtosis imaging (Aim 2) and a functional MRI task to measure alcohol cue-induced functional connectivity in the MPFC-striatal circuit. Cutting-edge methodologies will be used to analyze the data presented in this proposal, including: voxel-based morphometry, electrical field modeling, diffusion kurtosis imaging, functional connectivity analysis, and multivariate statistics. The candidate will incorporate guidance from experts in neuroimaging and AUD (Drs. Hanlon and Jensen) to evaluate these aims.