Effects of tDCS Paired with Cognitive Training on Brain Networks associated with Alcohol Use Disorder in Veterans

酗酒在美国退伍军人中很流行。近三分之一的退伍军人一生 酒精使用障碍（AUD）。在退伍军人和平民中，大约60%的人进入 治疗一年内复发。自相矛盾的是，长期饮酒与认知能力有关 他们潜在的神经回路的损伤和变化，干扰了他们所需的适应行为， 成功复苏。然而，这些认知障碍及其潜在的神经基质是 有希望的干预新目标可以降低复发率。有证据表明认知训练 可以改善AUD患者的认知，加强神经网络介导的认知， 治疗结果然而，认知训练是努力密集型的，具有小的效应大小，并且可能具有有限的 耐久性 有证据表明，成瘾是由功能失调的皮质-纹状体神经回路介导的， 过度的纹状体活动（驱动物质使用）加上前额叶皮质功能减退（认知功能受损 静息状态功能连通性（RSFC）数据已经确定了一个有前途的基于电路的目标， 成瘾的治疗长期戒酒的人（约7年） 禁欲）在前额叶介导的网络（例如前额叶-纹状体，前额叶-顶叶， 前额叶-岛叶，前额叶-丘脑网络）与对照组或短期禁欲（6-10周）的人相比 禁欲）。此外，短期戒断期间较低的前额叶RSFC可以预测随后的复发。 本研究的主要目的是研究一种新的基于神经可塑性的干预方法的使用， 结合认知训练和经颅直流电刺激（tDCS）神经调节， 额-纹状体RSFC和认知，目的是改善治疗结果并增加 有AUD的人。 这项研究计划将解决以下具体目标（SA）：SA 1）比较大脑网络的变化 当两组都接受认知训练时，活性tDCS与假tDCS（安慰剂）组之间的差异。RSFC 将使用术前和术后收集的功能性磁共振成像数据测量变化， 干预后。 假设： 与假tDCS相比，活性tDCS将产生显著更大的 前额叶-纹状体RSFC增加。 SA 2）评价活性tDCS与假tDCS之间的认知变化 （安慰剂）组。 假设： 与假tDCS相比，活性tDCS将产生显著更大的 认知性能指标的改善。 SA 3）比较活性tDCS相对于假tDCS对 饮酒行为超过2个月的随访期。 我们的主要结果将是比较狂饮日数 在干预后2个月内，接受活性tDCS的AUD参与者与 假的 假设： 与假tDCS相比，活性tDCS将显著减少狂饮天数 在干预后的2个月内每周。 认知障碍及其潜在的神经机制影响酒精成瘾治疗结果。我们 我提出了第一项研究，以研究tDCS增强的认知训练如何影响认知及其相关的 退伍军人酒精使用障碍的脑回路，这将为指导未来的研究提供关键信息。 和治疗发展。

Alcohol misuse is an epidemic among Veterans in the United States. Nearly 1/3 of Veterans have a lifetime history of Alcohol Use Disorder (AUD). Across Veteran and civilian populations, about 60% of those entering treatment will relapse within one year. Paradoxically, chronic alcohol use is associated with cognitive impairments and changes in their underlying neural circuitry, that interfere with adaptive behavior needed for successful recovery. However, these cognitive impairments and their underlying neural substrates are promising new targets for interventions that can reduce relapse rates. Evidence suggests that cognitive training can improve cognition in individuals with AUD, strengthen neural networks mediating cognition, and improve treatment outcome. However, cognitive training is effort intensive, has small effect sizes, and may have limited durability. Evidence suggests that addiction is mediated by a dysfunctional cortico-striatal neurocircuitry characterized by excess striatal activity (driving substance use) coupled with hypoactive prefrontal cortex (impaired cognitive control)​.​ Resting-state functional connectivity (RSFC) data has identified a promising circuit-based target for the treatment of addiction. Individuals who have achieved long-term abstinence from alcohol (~7 years of abstinence) have higher RSFC in prefrontally-mediated networks (e.g. prefrontal-striatal, prefrontal-parietal, prefrontal-insular, prefrontal-thalamic networks) th​an controls or those with short-term abstinence (6-10 weeks of abstinence). Moreover, lower prefrontal RSFC during short-term abstinence can predict subsequent relapse. The ​primary objective​ of this study is to investigate the use of a novel neuroplasticity based intervention that combines ​cognitive training​ and ​transcranial direct current stimulation ​(tDCS) neuromodulation​ to enhance frontal-striatal RSFC and cognition, with the goal to improve treatment outcomes and increase abstinence in Veterans with AUD. This research proposal will address the following ​Specific Aims (SAs)​: ​SA1) ​Compare brain network changes between active tDCS vs. sham tDCS (placebo) groups, ​when both groups receive cognitive training​. RSFC changes will be measured with functional magnetic resonance imaging data collected pre- and post-intervention. ​Hypothesis:​ ​Active tDCS, compared to sham tDCS will produce a significantly greater increase in prefrontal-striatal RSFC. ​SA2) ​Evaluate cognitive changes between active tDCS vs. sham tDCS (placebo) groups. ​Hypothesis:​ ​Active tDCS, compared to sham tDCS, will produce a significantly greater improvement in cognitive performance measures. ​SA3) ​Compare the effects of active tDCS vs. sham tDCS on drinking behavior over a 2 month follow-up period.​ ​Our primary outcome will be to compare binge drinking days per week​ w​ ithin the 2 months after the intervention between AUD participants who receive active tDCS vs. sham. ​Hypothesis:​ ​Active tDCS, compared to sham tDCS, will produce significantly fewer binge drinking days per week​ i​ n the 2 months following the intervention. Cognitive impairment and its underlying neural mechanisms affect alcohol addiction​ treatment outcomes​. We propose the first study to examine how tDCS-augmented cognitive training affects cognition and its related brain circuitry in alcohol use disorder in Veterans, which will provide critical information to guide future research and treatment development.