The Repair of Self Control in Alcohol Dependence: Working Memory & Real Time fMRI

描述(申请人提供)：酒精依赖者经常有自我控制缺陷，这是通过对延迟奖励的过度折扣来衡量的。双重神经行为决策系统模型表明，这些缺陷可能是由于两个相互作用的神经生物系统之间的调节平衡被破坏所致。这些系统是负责评估延迟奖励(即长期目标)的执行系统(前额叶皮质和顶叶皮质)，以及与即时奖励(即即时满足感)相关的冲动系统(边缘和边缘旁区域)。我们最近的研究表明，工作记忆(WM)训练通过恢复这些系统之间的调节平衡来修复自我控制。然而，在修复自我控制方面，仍有很多东西需要学习。在目标1中，我们将进一步探讨WM训练对范围的影响 WM、自我控制和临床相关(例如，渴望)措施。此外，还将通过功能神经成像技术探索西医训练的神经机制。我们将通过系统地改变几组酒精依赖者的WM训练课程的数量来检验WM训练的剂量效应功能。通过在培训后1个月、3个月和6个月进行跟踪评估来测试这些自我控制能力提高的持续时间。在目标2中，我们计划利用在目标1中获得的神经生物学知识来测试两种不同的实时fMRI神经反馈对我们的WM套件、自我控制和临床意义测量的影响。这种对神经反馈对神经认知和临床意义的影响的新探索将包括基于特定大脑区域的反馈技术和跨分布式神经网络的反馈技术的直接比较。在为期一个月的随访中，我们将探讨神经功能和/或神经认知测量的长期变化。成功地实现我们的目标可以让我们既改进我们目前的技术(即WM训练)，也可能开始开发修复酒精依赖者自我控制的新技术(即神经反馈)的过程。这一应用将有助于酒精依赖的个性化药物治疗，其中治疗是通过记录的自我控制缺陷来定义的。此外，通过这两个目标收集的功能神经成像数据应该为酒精依赖中出现的神经破坏模式和与治疗相关的神经功能变化提供独特的见解。

DESCRIPTION (provided by applicant): Alcohol-dependent individuals frequently have deficits in self-control, as measured by their excessive discounting of delayed rewards. The dual neurobehavioral decision systems model suggests that these deficits may result from a disruption in the regulatory balance between two interacting neurobiological systems. These systems are the executive system (prefrontal cortex and parietal cortex) which is responsible for valuing delayed rewards (i.e., long-term goals), and the impulsive system (limbic and paralimbic areas) which is associated with immediate rewards (i.e., instant gratification). Our recent research has demonstrated that working memory (WM) training repairs self-control, putatively by restoring regulatory balance between these systems. There is, however, still much to learn about repairing self-control. In Aim 1, we will further explore the effects WM training on a range of WM, self-control, and clinically relevant (e.g., craving) measures. Additionally, the neural mechanisms of WM training will be explored though functional neuroimaging techniques. We will examine the dose-effect function of WM training by systematically varying the number of WM training sessions across several groups of alcohol-dependent individuals. The duration of these improvements in self-control will be tested by conducting follow-up assessments one month, three months, and six months after training. In Aim 2 we plan to capitalize on the neurobiological knowledge gained in Aim 1 to test the effects of two variants of real time fMRI neuro-feedback on our suite of WM, self-control, and clinically significant measures. This novel exploration of neuro-feedback effects on neurocognitive and clinically significant measures will include a direct comparison of feedback techniques based on a specific brain region and across a distributed neural network. Long-term changes in neural function and/or our neurocognitive measures will be explored during a one-month follow-up visit. Successfully achieving our aims could allow us to both refine our current techniques (i.e., WM training), and possibly begin the process of developing novel techniques (i.e., neuro-feedback) for the repair of self-control in alcohol-dependent individuals. This application will contribute to personalized medicine approaches in alcohol dependence, where treatment is defined by documented self-control deficits. Furthermore, the functional neuroimaging data collected across both aims should provide unique insights into both patterns of neural disruption seen in alcohol dependence and any treatment associated changes in neural function.