Functional Magnetic Resonance Imaging Of Emotion As Related To Alcoholism

与酗酒相关的情绪功能磁共振成像

• 批准号: 8344665
• 负责人: Daniel W Hommer
• 金额: $ 123.14万
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8344665
• 关键词: Address; Adolescent; Affect; Alcoholic beverage heavy drinker; Alcoholism; Alcohols; Amygdaloid structure; Animal Model; Anterior; Appearance; Arousal; Behavioral; Brain; Brain region; Categories; Communities; Comparative Study; Corpus striatum structure; Cues; Decision Making; Diagnosis; Disease; Dopamine; Elements; Emotions; Employee Strikes; Esthesia; Ethanol; Failure; Functional Magnetic Resonance Imaging; Human; Image; Impulsivity; Incentives; Individual; Inpatients; Judgment; Lead; Learning; Maintenance; Maps; Measurement; Measures; Methods; Modeling; Modification; Motivation; Motor; Neurobiology; Notification; Nucleus Accumbens; Outcome; Pathway interactions; Personality Traits; Personality inventories; Play; Preparation; Prosencephalon; Publishing; Punishment; Recruitment Activity; Reporting; Rewards; Risk; Role; Signal Transduction; Substance Use Disorder; Substance abuse problem; Syndrome; Ventral Striatum; Work; alcohol response; approach avoidance behavior; approach behavior; base; cognitive function; dopamine system; dopaminergic neuron; drug craving; expectation; externalizing behavior; improved; member; neural circuit; neuroimaging; non-alcoholic; non-drug; positive emotional state; problem drinker; relating to nervous system; response; reward processing; social; visual feedback; young adult

The largest portion of the SBEI efforts has involved fMRI studies of motivation. These involve examination of how the brain responds during the anticipation of working to gain reward or to avoid punishment as well as examination of how the brain responds to notification of the results of an attempt to gain reward or avoid punishment. We have used different versions of a monetary incentive delay (MID) task to study motivation. The SBEI developed this task 11 years ago and since then it has been widely used in the functional neuroimaging imaging community to study reward processing. In the basic version of the task subjects see a cue indicating that on the current trial they are working for money (e.g., $5.00, $1.00, or $.20) or for no money; next they wait for a variable delay, and then press a button in response to presentation of a target. If they respond before the target disappears, they win the money indicated at the start of the trial. If they are too slow they win nothing. The interval between appearance of the initial cue and the target cue signaling the need to make a response is considered to manifest the brain state underlying the motivation for the specific action and involves both elements of motor preparation as well as anticipation of gaining reward. Finally the subjects get visual feedback indicating if they successfully responded, how much they won or lost, and their total earnings. Brain response to this notification can be considered a measure of the significance of the outcome and is similar to the dopaminergic learning signal referred to as a prediction error signal. Multiple studies have shown that MID type tasks reliably activate the ventral striatum (VS) in response to cues that signal an imminent opportunity to respond for monetary rewards. The brain response is proportional to the amount of money at stake. Conversely, the VS is not as robustly recruited by cues for reward deliveries that require no behavioral response. In addition, the VS as well as ventral mesofrontal cortex (mFC) are activated by notification of reward, typically when contrasted with notification that there will be no reward. Thus, the MID task can provide measurements of an individuals sensitivity to anticipation of working for reward as well as sensitivity to notification that the reward has been won or lost. An individuals sensitivity to reward plays a major role in each of the two competing hypotheses about how alterations in brain function motivation lead to the acquisition and maintenance of alcoholism. One of these ideas, the reward deficiency syndrome (RDS) hypothesis, suggests that individuals predisposed to alcoholism (or substance use disorders in general) have a dysfunctional reward circuit which nondrug rewards fail to activate but which can be activated by the more powerful effect provided by addictive substances. In contrast, the competing idea, which we can call the impulsivity hypothesis, suggests that at risk individuals (as well as those currently addicted) have an increased sensitivity to reward in general combined with a failure of effective inhibition of approach behavior. For a detailed discussion of the evidence in favor and against these two hypotheses see the recent review by members of the SBEI on reward sensitivity. In order to directly examine reward sensitivity in alcoholism we compared inpatient alcoholics with healthy controls on a modified MID task that also allowed us to look at the effects of frustrating non-reward on brain oxygenation level dependent (BOLD) signal .We found no significant difference between alcoholics and controls during anticipation of responding for reward, and thus failed to find support for the RDS hypothesis. However, we did find evidence for increased sensitivity to notification of outcome in several brain regions of the alcoholics. These regions included the VS region that is usually activated by rewardinng outcome as well as a greater sensitivity to notification of loss in the anterior insular cortex. Perhaps most striking was a deactivation of the VS when alcoholics were notified that their response to win money was frustrated and they would have to repeat their response again. This effect scaled with the amount of money at stake. These results show that the VS of alcoholics is more sensitive to the mismatch between expectations and outcome than the VS of non-alcoholics. In addition, our findings are consistent with the idea that striatum and dopamine neurons play a critical role in prediction error. During the past few years we have published three studies on motivation among adolescents using the MID task. These studies showed a significant relationship between BOLD activation in striatum and sensation seeking and externalizing disorders. In addition they replicated our initial study of 2004 that showed a blunted activation in the VS of healthy adolescents compared to healthy young adults while they anticipated responding for reward. Recently, we again addressed the differences in brain response during the MID task between alcoholics and controls we first reported in 2008 using the improved methods described above as well as a modification of the task which allows us to more completely separate motor preparation from reward anticipation. We did this because there have been two reports that alcoholics have decreased anticipatory BOLD activation in VS compared to non-alcoholics while they prepare to respond to cues indicating the possibility of reward. As with our earlier report and it contrast to the reports of Beck and Wrase we found no difference in BOLD activation between alcoholics and controls while they prepared to respond to win money. In addition, when we compared anticipation of being notified of outcome following motor response we found less activation in VS among the alcoholics but this did not reach the threshold for statistical significance when compared with the response of the controls. Surprisingly we did not replicate the greater activation in response to outcome notification between alcoholics and controls we had reported previously. However we did find a significant correlation between impulsiveness measured by the NEO personality inventory and VS BOLD in response to successful outcome notification. Considered in their entirety we believe our recent work on imaging of motivation as related to the risk for alcoholism supports two conclusions: 1. The RDS hypothesis is less strongly supported than an alternative model involving greater sensitivity to reward receipt among alcoholics and individuals at risk for alcoholism. 2. This greater sensitivity does not directly map onto alcoholism as a diagnosis but rather is related to a set of personality traits comprising impulsiveness, sensation seeking and uninhibited externalizing behavior. It is possible that later in the course of alcoholism a kind of motivational blunting like that postulated in the RDS does develop. The we have continued to study the effects of intravenously on brain activation measured by fMRI. Intravenously administered ethanol is associated with a significant increase in BOLD signal in the ventral forebrain, including extended amygdala nucleus accumbens and ventral striatum. We are also beginning to explore how administration of alcohol affects risky decision-making in the brain. It appears that alcohol increases striatal activation during anticipation of responding for reward but blunts response to notification of the outcome of the motivated response. This is consistent with alcohol's ability to increase approach behavior while decreasing judgment and other higher cognitive functions. We have also examined BOLD response to alcohol in the VS of heavy and social drinkers. Heavy drinkers have a significantly blunted response in VS suggesting tolerance.

SBEI 的大部分工作涉及动机的功能磁共振成像研究。这些涉及检查大脑在预期努力获得奖励或避免惩罚期间如何反应，以及检查大脑如何响应尝试获得奖励或避免惩罚的结果通知。 我们使用不同版本的货币激励延迟（MID）任务来研究动机。 SBEI 在 11 年前开发了这项任务，从那时起它就被广泛应用于功能神经影像学界来研究奖励处理。 在任务的基本版本中，受试者会看到一条提示，表明在当前试验中他们正在为金钱（例如，5.00 美元、1.00 美元或 0.20 美元）工作或不赚钱；接下来，他们等待可变的延迟，然后按下按钮以响应目标的呈现。如果他们在目标消失之前作出回应，他们就会赢得试验开始时指定的金钱。 如果他们太慢，他们就什么也赢不了。初始提示和需要做出反应的目标提示之间的间隔被认为体现了特定动作动机背后的大脑状态，并且涉及运动准备以及获得奖励的预期这两个要素。最后，受试者会得到视觉反馈，表明他们是否成功回应、他们赢了或输了多少，以及他们的总收入。大脑对此通知的反应可以被认为是结果重要性的衡量标准，并且类似于被称为预测误差信号的多巴胺能学习信号。 多项研究表明，MID 类型的任务能够可靠地激活腹侧纹状体 (VS)，以响应暗示即将有机会对金钱奖励作出反应的线索。 大脑的反应与所涉金额成正比。 相反，VS 并不会因为不需要行为反应的奖励传递而被强有力地招募。此外，VS 以及腹侧中额叶皮层 (mFC) 会被奖励通知激活，通常与没有奖励的通知相比。因此，MID 任务可以测量个人对为奖励而工作的预期的敏感度以及对已赢得或失去奖励的通知的敏感度。 在关于大脑功能动机的改变如何导致酗酒的获得和维持的两个相互竞争的假设中，个体对奖励的敏感性起着重要作用。其中一个观点，即奖赏缺乏综合症（RDS）假说，表明易患酗酒（或一般物质使用障碍）的个体的奖赏回路功能失调，非药物奖赏无法激活该回路，但可以通过成瘾物质提供的更强大的作用来激活。相比之下，我们可以称之为冲动假说的竞争观点表明，处于危险中的个体（以及那些目前成瘾的人）总体上对奖励的敏感性增加，同时无法有效抑制接近行为。有关支持和反对这两种假设的证据的详细讨论，请参阅 SBEI 成员最近对奖励敏感性的审查。 为了直接检查酗酒者的奖励敏感性，我们在修改后的 MID 任务中将住院酗酒者与健康对照者进行了比较，该任务也使我们能够观察令人沮丧的无奖励对大脑氧合水平依赖 (BOLD) 信号的影响。我们发现，在预期奖励反应期间，酗酒者和对照者之间没有显着差异，因此未能找到对 RDS 假设的支持。然而，我们确实发现了酗酒者的几个大脑区域对结果通知的敏感性增加的证据。这些区域包括通常由奖励结果激活的 VS 区域，以及对前岛叶皮质损失通知的更高敏感性。也许最引人注目的是，当酗酒者被告知他们对赢钱的反应受到挫败并且他们将不得不再次重复他们的反应时，VS 被停用。这种效应随着所涉及的资金数额而增加。这些结果表明，酗酒者的 VS 对期望与结果之间的不匹配比非酗酒者的 VS 更敏感。此外，我们的研究结果与纹状体和多巴胺神经元在预测误差中发挥关键作用的观点是一致的。 在过去的几年中，我们发表了三项关于青少年使用 MID 任务的动机的研究。这些研究表明纹状体中的 BOLD 激活与感觉寻求和外化障碍之间存在显着关系。 此外，他们重复了我们 2004 年的初步研究，该研究表明，与健康的年轻人相比，健康青少年的 VS 激活较弱，同时他们预期对奖励做出反应。 最近，我们再次解决了酗酒者和对照组之间在 MID 任务期间大脑反应的差异，我们在 2008 年首次报道，使用上述改进的方法以及对任务的修改，使我们能够更完全地将运动准备与奖励预期分开。我们这样做是因为有两份报告表明，与非酗酒者相比，酗酒者在准备对表明奖励可能性的线索做出反应时，VS 中的预期 BOLD 激活有所减少。与我们之前的报告一样，与 Beck 和 Wrase 的报告相比，我们发现酗酒者和对照者在准备应对赢钱时的大胆激活没有差异。此外，当我们比较运动反应后收到结果通知的预期时，我们发现酗酒者的 VS 激活较少，但与对照组的反应相比，这并未达到统计显着性的阈值。令人惊讶的是，我们没有复制我们之前报告的酗酒者和对照组之间对结果通知的更大激活反应。然而，我们确实发现 NEO 性格量表测量的冲动性与 VS BOLD 响应成功结果通知的冲动性之间存在显着相关性。 综合考虑，我们相信我们最近关于与酗酒风险相关的动机成像的研究支持两个结论： 1. RDS 假说的支持不如另一种模型那么有力，该模型涉及酗酒者和有酗酒风险的个体对奖励接受的更高敏感性。 2. 这种更高的敏感性并不直接映射到酗酒作为诊断，而是与一系列人格特征有关，包括冲动、寻求感觉和不受抑制的外化行为。 有可能在酗酒的后期，确实会出现一种像 RDS 中假设的动机迟钝的情况。 我们继续研究静脉注射对通过功能磁共振成像测量的大脑激活的影响。静脉注射乙醇与腹侧前脑（包括扩展的伏核杏仁核和腹侧纹状体）的 BOLD 信号显着增加相关。我们还开始探索饮酒如何影响大脑的危险决策。看来，酒精会在预期对奖励作出反应期间增加纹状体激活，但会减弱对动机反应结果通知的反应。这与酒精增加接近行为同时减少判断力和其他高级认知功能的能力是一致的。 我们还研究了重度饮酒者和社交饮酒者的 VS 对酒精的大胆反应。大量饮酒者的 VS 反应明显迟钝，表明存在耐受性。