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

基本信息

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
项目类别：
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

项目摘要

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）：可卡因滥用和依赖是慢性、复发性疾病，几乎没有有效的治疗方法。长期接触药物后额叶和皮层下神经回路的变化可能会在戒烟后持续数年，并且可能会损害成瘾者在接触药物相关线索时抑制药物寻求的能力。据称，注意力偏差修正（ABM）训练可以减少对显着药物刺激的注意力反应，并且已被证明可以有效治疗酒精依赖；然而，ABM 在治疗可卡因成瘾者方面的功效尚未得到实证确定。先前的研究表明，长期可卡因使用者除了对显着药物线索的神经元反应增强之外，在抑制控制期间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数据支持这两个研究方向，因为可卡因滥用和依赖 (CCA) 个体对现实可卡因线索的反应表现出激活增加，而在抑制控制期间则表现出严重缺乏激活。尽管存在这两种神经元异常的广泛证据，但迄今为止，我们还不知道有一项研究直接比较了这两个指标（即增强的线索反应性和减少的抑制控制）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证据表明，相对于对照组，CCA 中额叶皮层下回路内的内在神经元活动（功能连接；fcMRI）有所增加。因此，当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 治疗可卡因成瘾的功效和作用机制（目标 1）。其次，我们将确定三种神经元异常中的哪一种（即提示反应性增强或抑制控制降低或 fcMRI 增加）更能预测复发和药物利用（探索性目标 1）。为了实现这两个目标，四十名寻求治疗的 CCA 将以盲法方式随机分配到两组中的一组：五次 ABM 治疗或五次类似的分类控制任务。所有参与者都将完成广泛的临床和功能磁共振成像电池治疗前和治疗后，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 将被证明能有效减少复发，并将在减少与成瘾有关的额叶（眶额皮质和前扣带回）和皮层下（腹侧纹状体）区域的 fcMRI 和提示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 增加的个体更有可能复发，这表明反复暴露于可卡因刺激可能会导致与药物刺激无关的潜在回路发生变化。这项研究的目标具有临床意义，因为它们有可能为 CCA 提供一种新的治疗方法，或者至少检查增加的 fcMRI、增强的线索反应性或减少的抑制控制是否更能预测复发。