Attentional bias and reward sensitivity in heavy binge drinkers

酗酒者的注意力偏差和奖励敏感性

• 批准号: 9169919
• 负责人: Monica Faulkner
• 金额: $ 3.48万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9169919
• 关键词: Acute; Addictive Behavior; Address; Age; Alcohol consumption; Alcohol or Other Drugs use; Alcoholism; Alcohols; Amino Acids; Attention; Behavioral; Brain; Clinical; Corpus striatum structure; Cues; Data; Diagnosis; Disease; Dopamine; Double-Blind Method; Early identification; Exhibits; Heavy Drinking; Heroin; Human; Hypersensitivity; Incentives; Intervention; Knowledge; Laboratories; Lead; Light; Magnetic Resonance Imaging; Measures; Mediating; Methadone; Methods; Neurobiology; Nucleus Accumbens; Opiates; Outcomes Research; Pattern; Pharmaceutical Preparations; Pharmacology; Phase; Phenylalanine; Placebo Control; Play; Population; Populations at Risk; Predisposition; Prefrontal Cortex; Prevention; Process; Property; Publishing; Recording of previous events; Reporting; Resources; Rest; Rewards; Risk; Role; Salvelinus; Sampling; Seeds; Severities; Stimulus; Substance Use Disorder; Substance of Abuse; System; Testing; Treatment Protocols; Treatment outcome; Tyrosine; Ventral Tegmental Area; Work; addiction; alcohol cue; alcohol misuse; alcohol reward; alcohol use disorder; attentional bias; attentional control; base; behavior test; behavioral response; binge drinker; binge drinking; conditioning; craving; directed attention; dopamine system; drug craving; emerging adult; functional MRI scan; improved; in vivo; neural circuit; neuromechanism; non-drug; novel; novel marker; public health relevance; relating to nervous system; response; sensory stimulus; social; theories; visual stimulus; ward; young adult

 DESCRIPTION (provided by applicant): Attentional bias (AB) is the excess allocation of attention toward a particular stimulus type, a phenomenon that can be readily measured in laboratory paradigms. Among people with substance use disorders (SUDs), including alcohol use disorders (AUDs), AB toward drug-related stimuli is widely reported. Such "addiction AB" is of clinical importance as it has been reported to correlate with drug craving, addiction severity, and treatment outcomes. Addiction AB is thought to reflect incentive sensitization processes associated with repeated pairing of sensory stimuli with the rewarding properties of reinforcing substances. Pairing non-drug rewards with simple geometric visual stimuli can also elicit AB toward these reward-paired cues ("reward-driven" AB) during brief laboratory conditioning. This is true for healthy young adults with no SUD history, and for methadone maintained heroin addicts, such reward-driven AB is greatly magnified. Reward-driven AB has not yet been investigated in other SUD (or at-risk) populations, and the relationship between addiction AB and reward-driven AB is unknown. Moreover, no studies to date have investigated the neural mechanisms of reward-driven AB. We hypothesize that a generalized hypersensitivity of the attention system to reward-related stimuli underlies both forms of AB. Published work from other labs, and our own preliminary data show that heavy, binge drinkers exhibit AB to alcohol cues. We predict that reward-driven AB will also be elevated in heavy, binge drinkers compared to moderate drinkers. Thus, the proposed study will first investigate the relationship between AB to alcohol cues and reward-driven AB in heavy binge drinkers versus moderate drinkers (Aim 1). In addition, we hypothesize that reward-driven AB is mediated by reward-predicting phasic dopamine (DA) release from the ventral tegmental area (VTA) projections to the nucleus accumbens (NAc), which are triggered or otherwise regulated by the prefrontal cortex (PFC). Thus, we will measure the effect of dampening phasic DA release, via an established amino acid depletion method, on reward-driven AB, comparing heavy binge-drinkers to moderate drinkers (Aim 2). Finally, as a first step toward identifying the neural circuit bases of reward-driven AB we will measure functional connectivity of the VTA with frontal and striatal regions from brief, resting-state fMRI scans collected immediately prior to behavioral testing, comparing DA depleted and control session data (Aim 3). We predict that DA depletion will reduce reward-driven AB, and that the magnitude of this behavioral change will be associated with reduced connectivity of the VTA with frontal nodes and/or increased connectivity with the NAc. This work may ultimately lead to the identification of generalized abnormalities in reward sensitivity associated with heavy, binge drinking that may increase susceptibility to, or maintain, addictive behaviors. An understanding of these neural processes is fundamental to determining how the brain enables us to attend and respond to environmental stimuli of value and may ultimately have implications for treating addictive disorders.

 描述(由申请人提供)：注意偏差(AB)是将注意力过度分配给特定刺激类型，这是一种可以在实验室范例中容易测量的现象。在有物质使用障碍(SODS)的人中，包括酒精使用障碍(AUDS)，AB对药物相关刺激的反应被广泛报道。这种“成瘾AB”具有临床重要性，因为据报道，它与药物渴求、成瘾严重程度和治疗结果有关。成瘾AB被认为反映了与反复将感觉刺激与增强物质的有益特性配对相关的激励敏化过程。将非药物奖赏与简单的几何视觉刺激配对，也可以在短暂的实验室条件作用下诱导AB对这些奖赏配对线索(“奖赏驱动”AB)。对于没有SUD病史的健康年轻人来说是这样的，对于美沙酮维持海洛因成瘾者来说，这种奖励驱动的AB被大大放大了。奖赏驱动型AB在其他SUD(或风险)人群中尚未被研究，成瘾AB和奖赏驱动型AB之间的关系尚不清楚。此外，到目前为止，还没有研究探讨奖励驱动的AB的神经机制。我们假设，注意系统对奖赏相关刺激的普遍超敏是两种AB形式的基础。其他实验室发表的研究，以及我们自己的初步数据显示，酗酒者表现出AB对酒精的暗示。我们预测，与适度饮酒者相比，重度酗酒者的奖励驱动型AB也会升高。因此，这项拟议的研究将首先调查重度酗酒者和中度饮酒者的AB与酒精暗示和奖励驱动AB之间的关系(目标1)。此外，我们假设奖赏驱动的AB是由奖赏预测相多巴胺(DA)从腹侧被盖区(VTA)投射到伏核(NAC)介导的，这是由前额叶皮质(PFC)触发或以其他方式调节的。因此，我们将通过一种已建立的氨基酸耗竭方法来测量抑制相DA释放对奖励驱动型AB的影响，将重度酗酒者与中度饮酒者进行比较(目标2)。最后，作为确定奖励驱动的AB神经回路基础的第一步，我们将从行为测试之前收集的简短、静止状态的fMRI扫描中测量VTA与额叶和纹状体区域的功能连通性，比较DA耗尽和对照会话数据(目标3)。我们预测，DA耗竭将减少奖励驱动的AB，这种行为变化的幅度将与VTA与额叶节点的连接减少和/或与NAC的连接增加相关。这项工作最终可能导致识别与酗酒有关的奖赏敏感度的普遍异常，这可能会增加或维持成瘾行为的易感性。对这些神经过程的了解是确定大脑如何使我们能够注意和响应有价值的环境刺激的基础，并可能最终对治疗成瘾障碍产生影响。