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

评估神经结构作为 AUD 中 TMS 功效的新型生物标志物

• 批准号: 10176137
• 负责人: Daniel McCalley
• 金额: $ 4.6万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10176137
• 关键词: Adherence; Aftercare; Alcoholic Beverages; Alcohols; Anisotropy; Architecture; Attenuated; Biological Markers; Brain; Cessation of life; Chronic; Clinical; Clinical Trials; Cocaine Users; Communication; Corpus striatum structure; Cues; Data; Data Set; Development; Diffusion; Disease; Electromagnetics; Fellowship; Financial Hardship; Functional Magnetic Resonance Imaging; Gender; Goals; Human; Image; Individual; Intervention; Laboratories; Linear Regressions; MRI Scans; Measures; Medial; Medical; Medical Care Costs; Meta-Analysis; Methodology; Methods; Modeling; Parents; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Physiologic pulse; Positioning Attribute; Prefrontal Cortex; Relapse; Research; Research Proposals; Resolution; Scalp structure; Scanning; Severities; Site; Societies; Structure; Testing; Therapeutic; Training; Transcranial magnetic stimulation; Travel; Treatment outcome; United States; Work; alcohol cue; alcohol intervention; alcohol research; alcohol response; alcohol use disorder; anatomic imaging; attenuation; base; cerebral atrophy; clinical biomarkers; clinical efficacy; connectome; craving; cue reactivity; drinking; drug seeking behavior; electric field; follow-up; gray matter; human subject; improved; interest; morphometry; neural circuit; neuroimaging; noninvasive brain stimulation; novel; novel marker; preclinical study; predictive marker; prevent; preventable death; recruit; relapse prediction; relating to nervous system; statistics; tool; tractography; white matter

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.

项目摘要 目前将酒精使用障碍（AUD）定位为可预防死亡的第三主要原因 美国，每年造成88,000人死亡。 2019年，与与医疗相关的盟军总费用 AUD超过2240亿美元。 AUD治疗工作中的一个共同目标是防止饮酒复发。 尽管可以使用几种药理治疗，但遵守这些治疗量很低，并且 在6个月内从事复发的个人中约有60％。此外，这些治疗方法 以相对全球的方式调节大脑。来自AUD患者的神经影像学研究的证据已表明 额叶神经循环响应于酒精提示，其活性升高，这可能随后 预测复发。因此，人们对发展新颖的神经电路特定治疗有一种新兴的兴趣 增强AUD治疗结果的工具。经颅磁刺激（TMS）是这样的非 侵入性，神经电路特定的工具。通过电磁诱导，可以应用TMS的重复脉冲 到MPFC改变刺激部位的神经活动，并可以沿着完整的白质区域传播到 改变下游连接（例如纹状体）中的神经活动。但是，众所周知 随着AUD的灰质体积（影响刺激部位）的广泛减少）以及 降低白质完整性（影响MPFC和纹状体之间的道路）。主要目标 该F31研究建议是确定灰质体积在MPFC中的影响（AIM 1）和 MPFC和纹状体之间的白质完整性（AIM 2）在TMS上相关的MPFC- 响应酒精提示的纹状体活性。此外，该建议计划将目标1和2与临床集成 aud的生物标志物，例如性别和饮酒严重性，以评估这些因素的相对贡献 在TMS相关的酒精提示引起的MPFC-纹状体活性的变化中。该提议得到了培训的补充 包括4个领域的计划：神经影像学分析，科学沟通，AUD的临床观点以及 多元统计。这项为期两年的F31奖学金将通过利用我们的现有数据集进行分析 实验室。该F31提案的父母临床试验招募了50名具有AUD的寻求治疗的人 在基线上接受MRI扫描，然后进行10天的真实TMS，然后在治疗后进行MRI扫描， 治疗后1个月，治疗后2个月。每个MRI扫描都由高分辨率解剖学组成 图像（AIM 1），扩散峰度成像（AIM 2）和功能性MRI任务，以测量酒精提示诱导的 MPFC-纹状体电路中的功能连通性。尖端方法将用于分析数据 在此提案中提出，包括：基于体素的形态计量学，电场建模，扩散峰度 成像，功能连接分析和多元统计。候选人将纳入指导 来自神经影像学专家和AUD（Hanlon和Jensen博士）来评估这些目标。