Neural mechanisms of CBT in cocaine dependence (Gender Differences Supplement)

描述（由申请人提供）：虽然目前还没有FDA批准的可卡因依赖药物，但行为疗法如认知行为疗法（CBT）具有强有力的经验支持以及效果的持久性。神经生物学因素的评价是一个很有前途的策略，评估经验支持的治疗机制，以及为治疗开发确定潜在的新目标。我们建议增加三个成像会议（治疗前，治疗后，和6个月的随访），以最近启动的随机临床试验，评估两种形式的CBT（治疗师和计算机提供）与手动引导的标准咨询96可卡因依赖的个人从母公司试验。使用从使用建议任务的初步数据中得出的假设（Stroop颜色词干扰和货币激励延迟任务）和测量（白色物质完整性、局部脑体积和静息状态脑功能），我们将：1）调查成像任务的基线测量预测治疗结果的程度; 2）评估治疗前后fMRI测量的变化（基线至12周）和按治疗条件列出（CBT与标准咨询）; 3）检查治疗期间脑激活变化与6个月随访结果的关系（重点是理解CBT的持久性和“睡眠者”效应）;以及4）调查大脑激活和CBT“剂量”（CBT会话和完成的作业）之间的关系。该项目利用了一个难得的机会来评估与成瘾治疗相关的神经作用机制，特别是CBT，以及一个独特的机会来检查CBT中与效果持久性（“睡眠者”效应）相关的神经因素。证明大脑激活的持久变化与CBT相关的认知控制改善并行，这将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，使临床医生能够将特定的技能和策略瞄准最有可能从中受益的个人。

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.