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

注意偏差修正：可卡因成瘾者的功效和作用机制

• 批准号: 8415517
• 负责人: Andrew Robert Mayer
• 金额: $ 19.36万
• 依托单位: THE MIND RESEARCH NETWORK
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8415517
• 关键词: Abstinence; Addictive Behavior; Aftercare; Alcohol dependence; Anterior; Attention; Behavior; Behavioral; Blinded; Brain; Cells; Chronic; Clinical; Cocaine; Cocaine Abuse; Cocaine Dependence; Cocaine Users; Cues; Data; Dependence; Development; Disease; Drug Exposure; Drug Utilization; Drug usage; Exhibits; Exposure to; Failure; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Goals; Grant; Human; Image; Individual; Intervention; Measurement; Measures; Medical; Metric; Modeling; Modification; Nature; Neurobiology; Neurologic; Neurons; Participant; Patients; Pharmaceutical Preparations; Placebos; Population; Process; Randomized; Relapse; Relative (related person); Research; Risk; Scanning; Societies; Stimulus; Substance abuse problem; Techniques; Therapeutic; Time; Training; United States National Institutes of Health; Ventral Striatum; Work; addiction; cingulate cortex; cingulate gyrus; clinically significant; cocaine exposure; cocaine use; cognitive control; craving; cue reactivity; effective therapy; frontal lobe; group intervention; improved; innovation; neural circuit; neuroimaging; neuronal circuitry; psychologic; relating to nervous system; response; social; theories; therapy design; treatment duration; treatment effect

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.

描述（由申请人提供）：可卡因滥用和依赖性是慢性，复发的疾病，几乎没有有效的治疗方法。延长药物暴露后，额叶和亚皮质神经回路的变化可能会持续数年，并可能损害瘾君子在暴露于药物相关线索时抑制药物寻求药物的能力。据称，注意偏置修饰（ABM）训练可以减少对显着药物刺激的注意力反应，并已被证明可以有效治疗酒精依赖性。但是，ABM在治疗可卡因成瘾的个体中的功效尚未得到经验确定。先前的研究表明，除了增强对显着药物提示的神经元反应外，慢性可卡因使用者在抑制性控制过程中还表现出降低的神经元反应。在我们的R03-ISTART赠款期间获得的初步神经影像学数据支持这两种研究，因为滥用可卡因和依赖性（CCA）的个体在响应现实的可卡因提示以及在抑制控制过程中严重缺乏激活而表现出增加的激活。尽管存在这两种神经元异常的广泛证据，但迄今为止，我们尚未意识到一项直接比较了这两个指标的差异有效性（即提高提示反应性和抑制性降低的抑制性对照）的研究，以预测复发。此外，我们的初步数据提供了相对于对照组中CCA的额叶亚皮质电路内固有神经元活性增加（功能连通性； FCMRI）的证据。因此，当前的应用程序具有两个主要目标，它们具有临床意义且高度创新。首先，我们将研究ABM在治疗可卡因成瘾中的作用的功效和机制（AIM 1）。其次，我们将确定三种神经元异常或异常中的哪一个（即提高提示反应性或抑制性控制降低或FCMRI增加）更可预测复发和药物利用率（探索性目标1）。为了实现这两个目标，40个寻求治疗的CCA将以盲目的方式随机分为两组之一：五个ABM治疗或类似分类控制任务的五个会议。所有参与者将完成广泛的临床和fMRI电池预处理前后，旨在测量可卡因提示处理，抑制性控制和功能连通性期间的激活。我们预测，ABM将被证明在减少复发方面有效，并且它将对降低额叶（轨道额叶皮层和前扣带回回）的FCMRI和提示反应性发挥最大的作用，并在下构成中涉及的肌层（腹侧纹状体）区域。我们还预测，在基线时额叶下皮层中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础电路的变化，而这些电路与暴露于药物刺激的情况下。这项研究的目标在临床上具有重要意义，因为它们可能会为CCA提供新的治疗方法，或者至少检查FCMRI增加，提高提示反应性或抑制性控制降低是否更可预测复发。

项目成果

Effects of attentional bias modification therapy on the cue reactivity and cognitive control networks in participants with cocaine use disorders.

注意偏差修正疗法对可卡因使用障碍参与者的提示反应性和认知控制网络的影响。

• DOI: 10.1080/00952990.2019.1671437
• 发表时间: 2020
• 期刊: The American journal of drug and alcohol abuse
• 作者: Mayer,AndrewR;Dodd,AndrewB;Wilcox,ClaireE;Klimaj,StefanD;Claus,EricD;Bryan,AngelaD
• 通讯作者: Bryan,AngelaD