Effects of Neuromodulation and Cognitive Training on Brain Networks Associated with Relapse in Alcohol Use Disorder

基于心理社会学的酒精使用障碍（AUD）治疗方案的复发率仍然很高。小说 需要基于大脑的干预来改善结果。针对潜在神经系统的干预措施 与复吸有关的网络在减少这一关键的公共卫生问题方面有着重大的希望。我 静息态功能连接（RSFC）数据显示，AUD（i）患者中， 长期戒断者有较高前额叶-纹状体RSFC，（ii）随后复发者表现出较低的前额叶-纹状体RSFC， 早期禁欲期间纹状体RSFC。我感兴趣的是研究前额叶-纹状体RSFC是否可以 在早期戒断期间进行修改，作为一种治疗形式，以防止随后的复发。我们有证据表明 经颅直流电刺激（tDCS）干预与认知训练配对， 增加大脑RSFC和改变行为。我们将进行一项双盲随机试验， 接受AUD治疗的受试者，以确定tDCS干预与认知 训练可以增加前额-纹状体RSFC，并减少随访期间的饮酒量。我们 还将研究RSFC变化是否与临床结局相关。核心假设是， 积极的tDCS结合认知训练将增加前额叶-纹状体RSFC，并减少 在6个月的随访期内使用酒精。本研究建议将解决以下具体问题： 目标：SA 1。比较主动与假tDCS干预对RSFC的影响。假设：主动tDCS， 与假手术相比，tDCS将产生前额叶-纹状体RSFC的最大增加。 SA 2.确定早期戒酒期间RSFC的变化是否会影响随访期间的酒精使用 (FC独立于tDCS干预的变化）。假设：前额叶-纹状体FC增加的程度将 与干预后6个月酒精使用量的减少相对应。SA 3.比较主动与被动的效果。 在6个月的随访期内对禁欲进行假tDCS干预。假设：主动tDCS，与 假tDCS将在干预后6个月产生较低的酒精使用。调查结果将提供关键证据 支持定制的基于大脑的干预措施的治疗用途， 支持戒酒的机制。 不 他的研究将提供一个适当的动力， 临床试验，未来的R 01应用，具有更大的样本量和更多的神经成像时间点，以提供信息 验证新的干预措施。结合我的职业发展计划和强大的指导团队， 该奖项将促进我成功过渡到独立作为一个调查员的知识和技能， 领导一个团队，将神经影像学发现与新的治疗干预措施相结合，以改善 物质使用障碍

Relapse rates in psychosocially-based treatment programs for alcohol use disorder (AUD) remain high. Novel brain-based interventions are needed to improve outcomes. Interventions that target the underlying neural networks associated with relapse hold significant promise in reducing this critical public health problem. My resting-state functional connectivity (RSFC) data showed that individuals with AUD (i) who have achieved long- term abstinence have higher prefrontal-striatal RSFC, and (ii) who subsequently relapse show low prefrontal- striatal RSFC during early abstinence. I am interested in investigating whether prefrontal-striatal RSFC can be modified during early abstinence as a form of treatment to prevent subsequent relapse. We have evidence that transcranial direct current stimulation (tDCS) interventions paired with cognitive training can significantly increase brain RSFC and modify behavior. We will conduct a double-blind randomized trial including 75 participants receiving treatment for AUD to determine whether a tDCS intervention combined with cognitive training can increase prefrontal-striatal RSFC and reduce amount of alcohol use during a follow-up period. We will also investigate whether RSFC changes are related to clinical outcomes. The central hypothesis is that active-tDCS combined with cognitive training will increase prefrontal-striatal RSFC and reduce amount of alcohol use during a 6-month follow-up period. This research proposal will address the following specific aims: SA1. Compare the effect of active- vs. sham-tDCS intervention on RSFC. Hypothesis: Active-tDCS, compared to sham-tDCS will produce greatest increase in prefrontal-striatal RSFC. SA2. Determine whether RSFC changes during early abstinence affect alcohol use during a follow-up period (FC changes independent of tDCS intervention). Hypothesis: Degree of prefrontal-striatal FC increases will correspond to reduction in alcohol use 6-months after intervention. SA3. Compare the effects of active- vs. sham-tDCS intervention on abstinence over 6-month follow-up period. Hypothesis: Active-tDCS, compared to sham tDCS will produce lower alcohol use 6-months after intervention. Findings will provide crucial evidence supporting the therapeutic use of customized brain-based interventions targeting underlying neural mechanisms to support alcohol abstinence. T his research will provide preliminary data for a properly powered clinical trial, a future R01 application with larger sample sizes and more neuroimaging time points to inform validated new interventions. Combined with my career development plan and strong mentoring team, this K award will foster my successful transition to independence as an investigator with the knowledge and skills to lead a team that converges neuroimaging findings with novel treatment interventions to improve outcomes in substance use disorders.