Neural mechanisms of CBT in cocaine dependence

描述(申请人提供)：虽然到目前为止还没有FDA批准的治疗可卡因依赖的药物，但认知行为疗法(CBT)等行为疗法具有强大的经验支持和效果的持久性。神经生物学因素的评估是评估经验性支持的治疗机制以及确定潜在的治疗开发新靶点的一种很有前途的策略。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阶段(治疗前、治疗后和6个月的随访)，评估两种形式的CBT(治疗师和计算机提供)与从父母试验中抽取的96名可卡因依赖者的手动指导标准咨询。使用来自初步数据的假设(Stroop颜色-单词干扰和货币诱因延迟任务)和测量(白质完整性、区域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)评估从治疗前到治疗后(基线到12周)和治疗条件(CBT与标准咨询)的fMRI测量的变化；3)检查治疗中大脑激活的变化与6个月随访结果的关系(重点是了解CBT的持久性和“睡眠”效应)；4)研究大脑活动与CBT“剂量”(CBT课程和家庭作业完成)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与CBT效果的持久性有关的神经因素(“睡眠”效应)。在认知控制方面与CBT相关的改善并行的大脑激活的持久变化的展示，将是阐明和加强治疗效果以及了解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人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.