Attentional Bias Modification: Efficacy and Mechanisms of Action in Cocaine Addic

描述(申请人提供)：可卡因滥用和依赖是慢性、复发性疾病，几乎没有有效的治疗方法。长期接触毒品后额叶和皮质下神经回路的变化可能会在戒毒后持续数年，并可能损害吸毒者在接触与毒品有关的线索时抑制寻求毒品的能力。注意力偏向修正(ABM)训练据称可以减少对显著药物刺激的注意反应，并已被证明在治疗酒精依赖方面是有效的；然而，ABM在治疗可卡因成瘾个人方面的有效性尚未得到经验证明。先前的研究表明，除了对显著药物线索的神经元反应增强外，慢性可卡因使用者在抑制控制过程中也表现出神经元反应的降低。在我们的R03-iStart赠款期间获得的初步神经成像数据支持这两种研究路线，因为可卡因滥用和依赖(CCA)患者表现出对现实可卡因提示的激活增加，而在抑制控制期间严重缺乏激活。尽管存在这两种神经元异常的广泛证据，但到目前为止，我们还没有发现一项研究直接比较这两种指标(即增强的线索反应性和降低的抑制性控制)在预测复发方面的差异有效性。此外，我们的初步数据提供了与对照组相比，颈总动脉额叶皮质下回路内固有神经元活动(功能连接；fcMRI)增加的证据。因此，目前的应用有两个主要目标，这两个目标都具有临床意义和高度创新。首先，我们将研究ABM治疗可卡因成瘾的疗效和作用机制(目标1)。其次，我们将确定三个神经元异常中的哪一个或哪一个异常(即，线索反应性增强、抑制性控制降低或功能磁共振成像增加)更能预测复发和药物使用(探索目标1)。为了实现这两个目标，40名寻求治疗的CCA将被随机分成两组中的一组：五次ABM治疗或五次类似分类对照任务。所有参与者将在治疗前和治疗后完成广泛的临床和功能磁共振成像电池，旨在测量可卡因线索处理、抑制控制和功能连接过程中的激活。我们预测，ABM将被证明在减少复发方面是有效的，它将在减少与成瘾有关的额叶(眼眶额叶和前扣带回)和皮质下(腹侧纹状体)区域的fcMRI和线索反应性方面发挥最大作用。我们还预测，基线时额叶、皮质下回路中fcMRI增加的个体将更有可能复发，这表明反复暴露于可卡因刺激可能会导致基本回路的改变，而这种改变独立于药物刺激的暴露。这项研究的目标具有临床意义，因为它们可能为CCA提供一种新的治疗方法，或者至少检查fcMRI增加、线索反应性增强或抑制控制减少是否更能预测复发。

DESCRIPTION (provided by applicant): Cocaine abuse and dependence are chronic, relapsing disorders for which there are few effective treatments. Changes in frontal and sub-cortical neural circuitry following prolonged drug exposure can last for years after cessation and may compromise an addict's ability to suppress drug seeking when exposed to drug- related cues. Attentional Bias Modification (ABM) training purportedly reduces the attentional response to salient drug stimuli and has been shown to be efficacious in treating alcohol dependence; however, the efficacy of ABM in treating individuals with cocaine addiction has yet to be empirically determined. Previous research suggests that chronic cocaine users also exhibit a decreased neuronal response during inhibitory control in addition to the enhanced neuronal response to salient drug cues. Preliminary neuroimaging data obtained during our R03-ISTART grant supports both lines of research, as individuals with cocaine abuse and dependence (CCA) exhibited increased activation in response to realistic cocaine cues and a profound lack of activation during inhibitory control. Although extensive evidence of these two neuronal abnormalities exists, to date we are not aware of a study that has directly compared the differential validity of these two metrics (i.e., enhanced cue reactivity and decreased inhibitory control) for predicting relapse. Additionally, our preliminary data provides evidence of increased intrinsic neuronal activity (functional connectivity; fcMRI) within a frontal sub-cortical circuit in CCA relative to controls. Therefore, the current application has two primary objectives that are both clinically significant and highly innovative. First, we will investigate the efficacy and mechanism of action of ABM in treating cocaine addiction (Aim 1). Second, we will determine which of the three neuronal abnormality or abnormalities (i.e., enhanced cue reactivity or decreased inhibitory control or increased fcMRI) are more predictive of relapse and drug utilization (Exploratory Aim 1). To achieve these two objectives, forty treatment-seeking CCA will be randomized to one of two groups in a blinded fashion: five sessions of ABM treatment or five sessions of a similar categorization control task. All participants will complete an extensive clinical and fMRI battery pre- and post-treatment designed to measure activation during cocaine cue processing, inhibitory control, and functional connectivity. We predict that ABM will prove to be efficacious in reducing relapse and that it will exert its greatest effect on reducing fcMRI and cue reactivity within frontal (orbital frontal cortex and anterior cingulate gyrus) and sub-cortical (ventral striatum) regions implicated in addiction. We also predict that individuals with increased fcMRI within frontal, sub-cortical circuits at baseline will be more likely to relapse, suggesting that repeated exposure to cocaine stimuli may result in changes in the underlying circuitry that are independent of exposure to drug stimuli. The goals of this study are clinically significant as they will potentially provide a new treatment for CCA or, at a minimum, examine whether increased fcMRI, enhanced cue reactivity or decreased inhibitory control are more predictive of relapse.