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

基于心理社会的酒精使用障碍(AUD)治疗计划的复发率仍然很高。小说 需要以大脑为基础的干预措施来改善结果。针对潜在神经的干预 与复发相关的网络在减少这一关键的公共卫生问题方面具有重大希望。我的 静息状态功能连接性(RSFC)数据显示，患有AUD(I)的人长期- 长期禁欲具有较高的前额叶-纹状体RSFC，以及(Ii)随后复发的人表现出较低的前额叶-纹状体RFC。 禁欲早期的纹状体RSFC。我有兴趣调查前额叶-纹状体RSFC是否可以 在早期禁欲期间进行修改，作为防止随后复发的一种治疗形式。我们有证据表明 经颅直流电刺激(Tdcs)干预配合认知训练可显著 增加大脑的RSFC，改变行为。我们将进行一项双盲随机试验，包括75 接受AUD治疗的参与者确定tdcs干预与认知相结合 训练可以增加前额叶-纹状体的RSFC，并在随访期减少酒精使用量。我们 还将调查RSFC的变化是否与临床结果有关。中心假设是 主动-tDCs结合认知训练可增加前额-纹状体RSFC，减少 在6个月的随访期内饮酒。这项研究提案将解决以下具体问题 目标：SA1。比较主动干预与假干预对RSFC的影响。假设：主动-tdcs， 与假手术组相比，TDC组前额-纹状体RSFC的增加幅度最大。 SA2.确定早期戒酒期间RSFC的变化是否会影响随访期的饮酒 (FC变化独立于tdcs干预)。假设：前额叶-纹状体FC增加的程度将 对应于干预后6个月酒精使用量的减少。SA3.比较主动与非主动的效果 在6个月的随访期内对戒酒进行假tdcs干预。假设：主动-tdcs，与 假tdcs在干预后6个月将产生较低的酒精使用量。调查结果将提供至关重要的证据 支持针对潜在神经的定制的基于大脑的干预措施的治疗使用 支持戒酒的机制。 T 他的研究将为适当的动力提供初步数据 临床试验，未来的R01应用具有更大的样本量和更多的神经成像时间点来通知 验证了新的干预措施。结合我的职业发展计划和强大的指导团队，这次K 获奖将帮助我成功地过渡到作为一名调查员的独立，拥有以下知识和技能 领导一个团队，将神经影像发现与新的治疗干预措施结合起来，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.