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

经颅直流电刺激 (tDCS) 与认知训练相结合对退伍军人酒精使用障碍相关大脑网络的影响

• 批准号: 9888838
• 负责人: KELVIN O. LIM
• 金额: --
• 依托单位: MINNEAPOLIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9888838
• 关键词: Abstinence; Adaptive Behaviors; Address; Affect; Alcohol dependence; Alcohol or Other Drugs use; Automobile Driving; Brain; Caring; Chiroptera; Clinical Trials; Cognition; Cognitive; Corpus striatum structure; Coupled; Data; Diagnosis; Effectiveness; Epidemic; Functional Magnetic Resonance Imaging; Future; Goals; Healthcare Systems; Impaired cognition; Individual; Inpatients; Intervention; Intervention Studies; Measures; Mediating; Neuronal Plasticity; Parietal; Participant; Patients; Population; Prefrontal Cortex; Randomized; Recording of previous events; Recovery; Relapse; Research Proposals; Rest; Testing; Thalamic structure; Time; Treatment outcome; United States; Veterans; Yang; addiction; alcohol abstinence; alcohol misuse; alcohol use disorder; base; binge drinking; brain circuitry; chronic alcohol ingestion; cognitive change; cognitive control; cognitive performance; cognitive training; drinking behavior; follow-up; improved; neural circuit; neural network; neuromechanism; neuroregulation; novel; placebo group; post intervention; primary outcome; randomized controlled study; relating to nervous system; research and development; seal; therapy development; treatment program

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.

滥用酒精在美国退伍军人中是一种流行病。近 1/3 的退伍军人有一生 酒精使用障碍（AUD）病史。在退伍军人和平民中，大约 60% 的人进入 治疗一年内会复发。矛盾的是，长期饮酒与认知能力有关 其潜在神经回路的损伤和变化，干扰了所需的适应性行为 成功恢复。然而，这些认知障碍及其潜在的神经基础是 有望降低复发率的干预新目标。有证据表明认知训练 可以改善 AUD 患者的认知能力，增强介导认知能力的神经网络，并改善 治疗结果。然而，认知训练需要大量努力，效果较小，并且效果可能有限。 耐用性。 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，其特征是 过度的纹状体活动（驱动物质使用）加上前额皮质功能低下（认知受损） 控制）​.​ 静息态功能连接（RSFC）数据已经确定了一个有前景的基于电路的目标 成瘾的治疗。已实现长期戒酒（约 7 年）的个人 禁欲）在前额介导的网络（例如前额叶-纹状体、前额叶-顶叶、 前额叶-岛叶网络、前额叶-丘脑网络）比对照组或短期戒酒者（6-10 周） 的禁欲）。此外，短期戒断期间前额叶 RSFC 的降低可以预测随后的复发。 本研究的​主要目的​是研究一种基于神经可塑性的新型干预措施的使用，该干预措施 结合​认知训练​和​经颅直流电刺激​(tDCS) 神经调节​来增强 额叶-纹状体 RSFC 和认知，目标是改善治疗结果并提高戒断率 退伍军人用澳元。 该研究提案将解决以下​具体目标 (SA)​：​SA1) ​比较大脑网络变化 主动 tDCS 组与假 tDCS（安慰剂）组之间的比较，​当两组都接受认知训练时​。 RSFC 将使用预先收集的功能磁共振成像数据来测量变化 干预后。假设：与假 tDCS 相比，主动 tDCS 会产生显着更大的 前额叶-纹状体 RSFC 增加。 ​SA2)​评估主动 tDCS 与假 tDCS 之间的认知变化 （安慰剂）组。假设：与假 tDCS 相比，主动 tDCS 会产生显着更大的 认知表现测量的改善。 ​SA3)​比较主动 tDCS 与假 tDCS 对 2 个月随访期间的饮酒行为。​ ​我们的主要结果是比较酗酒天数 接受主动 tDCS 的 AUD 参与者与接受主动 tDCS 的 AUD 参与者之间的干预后 2 个月内每周​ 假。假设：与假 tDCS 相比，主动 tDCS 会导致酗酒天数显着减少 干预后 2 个月内每周一次。 认知障碍及其潜在的神经机制影响酒精成瘾的治疗结果。我们 提出第一项研究来检验 tDCS 增强认知训练如何影响认知及其相关 退伍军人酒精使用障碍的大脑回路，这将为指导未来的研究提供关键信息 和治疗的发展。