Attentional bias and reward sensitivity in heavy binge drinkers

 描述（由申请人提供）：注意力偏差（AB）是对特定刺激类型的过度注意分配，这种现象可以在实验室范式中容易地测量。在物质使用障碍（SUD）患者中，包括酒精使用障碍（AUD），对药物相关刺激的AB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望，成瘾严重程度和治疗结果相关。成瘾AB被认为反映了与感官刺激与强化物质的奖励性质的重复配对相关的激励敏化过程。配对非药物奖励与简单的几何视觉刺激也可以引发AB对这些奖励配对线索（“奖励驱动”AB）在简短的实验室条件反射。 这对于没有SUD病史的健康年轻人来说是真实的，对于美沙酮维持的海洛因成瘾者来说，这种奖励驱动的AB被大大放大。奖励驱动型AB尚未在其他SUD（或风险）人群中进行研究，成瘾AB和奖励驱动型AB之间的关系尚不清楚。 此外，迄今为止还没有研究探讨奖励驱动型AB的神经机制。我们假设，一个普遍的超敏反应的注意系统奖励相关的刺激的基础上的两种形式的AB。 其他实验室发表的研究成果和我们自己的初步数据表明，酗酒者对酒精的反应是AB型。我们预测，与适度饮酒者相比，重度、狂欢饮酒者的奖励驱动型AB也会升高。因此，拟议的研究将首先调查AB酒精线索和奖励驱动的AB之间的关系，在重度酗酒者与中度饮酒者（目标1）。此外，我们假设，奖励驱动的AB介导的奖励预测阶段性多巴胺（DA）释放腹侧被盖区（VTA）的投射到脑桥核（NAc），这是触发或以其他方式调节的前额叶皮层（PFC）。因此，我们将测量阻尼阶段DA释放的影响，通过一个既定的氨基酸消耗方法，奖励驱动的AB，比较重度暴饮者适度饮酒（目标2）。最后，作为识别奖励驱动型AB的神经回路基础的第一步，我们将测量VTA与额叶和纹状体区域的功能连接，这些功能连接来自行为测试前即刻收集的简短的静息状态fMRI扫描，比较DA耗尽和控制会话数据（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。这项工作可能最终导致识别奖励敏感性的普遍异常，与重度，酗酒，可能会增加易感性，或维持，成瘾行为。了解这些神经过程对于确定大脑如何使我们能够关注和响应有价值的环境刺激至关重要，并可能最终对治疗成瘾性疾病产生影响。

 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.