Neural mechanisms of CBT in cocaine dependence

描述（由申请人提供）：虽然目前还没有fda批准的治疗可卡因依赖的药物，但行为疗法，如认知行为疗法（CBT）有很强的经验支持和效果的持久性。神经生物学因子的评估是一种有前途的策略，用于评估经验支持的治疗机制，以及确定治疗开发的潜在新靶点。我们建议在最近启动的一项随机临床试验中增加三个成像疗程（治疗前、治疗后和6个月的随访），以评估两种形式的CBT（治疗师和计算机提供）与手工指导的标准咨询对96名可卡因依赖个体的影响。通过使用拟议任务（Stroop颜色-单词干扰和货币激励延迟任务）和测量（白质完整性，区域脑容量和静息状态脑功能）的初步数据得出的假设，我们将：1)调查成像任务的基线测量在多大程度上预测治疗结果；2)评估治疗前后（基线至12周）和治疗情况（CBT与标准咨询）fMRI测量的变化；3)检查治疗内脑活动变化与6个月随访结果的关系（重点了解CBT的持久性和“睡眠者”效应）；4)研究脑活动与CBT“剂量”（CBT课程和完成的作业）之间的关系。这个项目利用了一个难得的机会来评估与成瘾治疗特别是CBT相关的神经机制，以及一个独特的机会来检查与CBT效果持久性（“睡眠者”效应）相关的神经因素。证明大脑活动的持久变化与CBT相关的认知控制的改善是阐明和加强治疗效果的重要一步，也是理解CBT的作用机制的重要一步，使临床医生能够针对最有可能从中受益的个体制定特定的技能和策略。

DESCRIPTION (provided by applicant): While there are as of yet no FDA-approved medications for cocaine dependence, behavioral therapies such as cognitive-behavioral therapy (CBT) have strong empirical support as well as durability of effects. Evaluation of neurobiological factors is a promising strategy for evaluating mechanisms of empirically supported therapies, as well as for identifying potentially novel targets for treatment development. We propose to add three imaging sessions (pre-treatment, post-treatment, and 6-month follow-up) to a recently initiated randomized clinical trial evaluating two forms of CBT (therapist- and computer-delivered) versus manual-guided standard counseling for 96 cocaine-dependent individuals drawn from the parent trial. Using hypotheses derived from preliminary data using the proposed tasks (Stroop Color-Word Interference and Monetary Incentive Delay Tasks) and measures (white matter integrity, regional brain volumes and resting state brain function), we will: 1) investigate the extent to which the baseline measures of the imaging tasks predict treatment outcomes; 2) evaluate changes in fMRI measures from pre- to post-treatment (baseline to 12 weeks) and by treatment condition (CBT versus standard counseling); 3) examine the relationship of within- treatment change in brain activation to 6-month follow-up outcomes (with an emphasis on understanding CBT's durability and "sleeper" effect); and 4) investigate the relationships between brain activations and CBT "dosing" (CBT sessions and homework completed). This project leverages a rare opportunity to evaluate neural mechanisms of action associated with addiction treatment in general and CBT in particular, as well as a unique opportunity to examining neural factors related to the durability of effects ("sleeper" effects) in CBT. Demonstration of durable changes in brain activation paralleling CBT-related improvements in cognitive control would represent an important step in elucidating and strengthening treatment effects, as well as understanding CBT's mechanisms of action, enabling clinicians to target specific skills and strategies to the individuals most likely to beneit from them.