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

描述（由申请人提供）：可卡因滥用和依赖是慢性、复发性疾病，很少有有效的治疗方法。额叶和皮层下神经回路在长期药物暴露后的变化可在戒烟后持续数年，并可能损害成瘾者在暴露于药物相关线索时抑制药物寻求的能力。注意偏倚修正（ABM）训练据称减少了对显著药物刺激的注意反应，并已被证明对治疗酒精依赖有效；然而，ABM在治疗可卡因成瘾个体方面的功效尚未得到实证的确定。先前的研究表明，在抑制控制期间，慢性可卡因使用者除了对显著药物线索的神经元反应增强外，还表现出神经元反应减弱。在我们的R03-ISTART资助期间获得的初步神经影像学数据支持这两方面的研究，因为可卡因滥用和依赖（CCA）的个体在对现实可卡因线索的反应中表现出增加的激活，而在抑制控制期间表现出严重的缺乏激活。尽管存在这两种神经元异常的广泛证据，但迄今为止，我们还没有发现一项研究直接比较了这两种指标（即线索反应性增强和抑制控制减弱）预测复发的差异有效性。此外，我们的初步数据提供了证据表明，相对于对照组，CCA患者额叶皮层下回路的内在神经元活动（功能连通性；fcMRI）有所增加。因此，目前的应用有两个主要目标，既具有临床意义，又具有高度创新性。首先，我们将研究ABM治疗可卡因成瘾的疗效和作用机制（Aim 1）。其次，我们将确定三种神经元异常或异常中的哪一种（即线索反应性增强或抑制控制减弱或fcMRI升高）更能预测复发和药物使用（探索性目标1）。为了实现这两个目标，40名寻求治疗的CCA将以盲法方式随机分为两组：5次ABM治疗或5次类似的分类控制任务。所有参与者将完成广泛的临床和功能磁共振成像电池前和后处理，旨在测量可卡因线索处理，抑制控制和功能连接期间的激活。我们预测ABM将被证明在减少复发方面是有效的，并且它将在减少与成瘾有关的额叶（眶额叶皮层和前扣带回）和皮层下（腹侧纹状体）区域的fcMRI和线索反应性方面发挥最大的作用。我们还预测，在基线时额叶和皮层下回路中fmri升高的个体更有可能复发，这表明反复暴露于可卡因刺激可能导致潜在回路的变化，而这种变化与暴露于药物刺激无关。本研究的目的具有临床意义，因为它们可能为CCA提供一种新的治疗方法，或者至少可以检查是否增加的fcMRI，增强的线索反应性或减少的抑制控制更能预测复发。

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.