fMRI Study of Cognition, Motivation, Decision-Making, Reward, Risk, Aversion, Craving, impulsivity, and Stress in Alcohol Use Disorder

酒精使用障碍中认知、动机、决策、奖励、风险、厌恶、渴望、冲动和压力的功能磁共振成像研究

• 批准号: 10007317
• 负责人: Abdolreza Momenan
• 金额: $ 91.13万
• 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/10007317
• 关键词: Affective; Alcohol consumption; Alcohol dependence; Alcoholic beverage heavy drinker; Alcoholism; Alcohols; Alleles; Amygdaloid structure; Anterior; Anti-inflammatory; Anxiety; Area; Behavioral; Biological Markers; COMT gene; Case-Control Studies; Clinical; Cognition; Cognitive; Collaborations; Comorbidity; Control Groups; Corpus striatum structure; Cross-Sectional Studies; Cues; Data; Decision Making; Dorsal; Double-Blind Method; Extinction (Psychology); Failure; Follow-Up Studies; Food; Fright; Functional Magnetic Resonance Imaging; Future; Genetic; Genetic Variation; Genomics; Goals; Grouping; Hares; Hippocampus (Brain); Impulsivity; Incentives; Individual; Inpatients; Insula of Reil; Investigational Therapies; Light; Major Depressive Disorder; Measures; Medial; Mental disorders; Minor; Morals; Motivation; Motor; Neurons; Nucleus Accumbens; Participant; Patient Self-Report; Patients; Persons; Pharmaceutical Preparations; Phase; Pioglitazone; Placebos; Precentral gyrus; Prefrontal Cortex; Process; Randomized; Reporting; Resistance; Rewards; Risk; Role; Sensory; Severities; Shock; Stimulus; Stress; Testing; Transcranial magnetic stimulation; Variant; Ventral Striatum; alcohol abuse therapy; alcohol cue; alcohol seeking behavior; alcohol use disorder; blood oxygenation level dependent response; caudate nucleus; cognitive function; conditioned fear; craving; depressive symptoms; discount; discounting; early life stress; financial incentive; genetic variant; high reward; memory recall; neural correlate; neurofeedback; novel; perceived stress; placebo group; problem drinker; putamen; relating to nervous system; response; reward anticipation; reward processing; risk variant; social; symposium; trait; translational study; treatment group; trend

1. Study of cognitive functions a. fMRI Studies of Socioemotional Processing. The purpose of this study is in part to examine differences in socioemotional processing related to AUD. We have conducted and presented interim analyses at scientific conferences. We found that Individuals with AUD compared to controls engaged in response inhibition via engagement of the ventral anterior cingulate and memory recall via engagement of the hippocampus during presentation of alcohol distractors alongside socioemotional stimuli. Similar effects were seen in the orbitofrontal cortex. Individuals with AUD had less engagement in moral processing regions (posterior cingulate, temporoparietal junction, and frontal pole) during presentation of alcohol distractors alongside moral stimuli. Similar effects seen in amygdala, medial prefrontal cortex, and temporal pole regions. These effects are more pronounced in individuals with greater alcohol consumption. These results suggest that alcohol cues interfere in cognitive and affective processing. b. Differences in discounting rates and neural processes involved in decision making between heavy drinkers vs. light drinkers will be tested in an upcoming study. This study will help understand these differences when the immediate and future reward involve either alcohol or money, and when these reward cues are presented in the context of negative and positive consequence stimuli. The results from this study may provide information regarding potential treatment targets for individuals with AUD to make less impulsive choices using approaches such as neurofeedback or transcranial magnetic stimulation persons. c. The interaction of cognitive and motor processes in alcoholics is currently being assessed using the inhibitory interference of response task (IIRT). This study will test this interaction by assessing the behavioral and neural response related to the inhibitory response in alcoholics and how it compares to healthy control participants. d. We are determining and studying neural correlates of decision making when making choices about whether to give money to charitable causes. Previous studies find that charitable decision making is associated with integration of value computing (from the ventral striatum) with social cognitive processing (such as in the insula and temporoparietal junction) through the ventromedial prefrontal cortex (vmPFC; e.g., Hare et al., 2010; Izuma et al., 2010; Tusche et al., 2016). The above mentioned regions have been implicated in AUD and our goal in conducting this study is whether such an fMRI task would provide further granularity in the decision making process of AUD patients as a biomarker. 2. fMRI Studies of Motivation a. In collaboration with Dr. Falk Lohoffs Section on Clinical Genomics and Experimental Therapeutics (CGET), we analyzed Monetary Incentive Delay (MID) task data to investigate if there were any association between a number of genetic variants implicated in psychiatric disorders the and activation in dorsal striatum during reward processing in patients with alcohol use disorder (AUD). i. Common MDD and AUD risk variant. AUD is often comorbid with other psychiatric disorders such as major depressive disorder (MDD). A locus in the TMEM161B-MEF2C region (rs10514299) has been identified as a risk variant for MDD. On the other hand, previous reports have shown the disruption of reward processing in both AD and MDD. We examined the association between rs10514299 and striatal BOLD responses during reward/loss anticipation in AUD. Patients carrying the T allele showed significantly greater putamen activation during anticipation of high reward and loss (high and low) avoidance, and a trend towards anticipation of low reward compared to healthy controls, HCs. (Muench et aL 2018) ii. Genetic Variation in COMT predicts reward processing in AUD. We have also collaborated with Dr. Lohoffs group to determine whether genetic variation in COMT in individuals with AUD and HCs is associated with differential striatal (caudate, putamen, nucleus accumbens) BOLD responses during reward processing. In this study, patients with AUD had showed significantly greater activation in regions of the ventral striatum during reward anticipation compared to controls. The AUD group also showed significantly greater activation in the caudate and nucleus accumbens during loss avoidance anticipation. Individuals with AUD who carry the minor T-allele showed significantly greater BOLD responses during reward anticipation compared to controls. This response was in opposite direction for the HCs. This finding points to the possibility using reward anticipation response as a biomarker of AUD in this variant of COMT gene. (Muench et al., 2018) b. Compulsivity and Reward Incentive Delay with Shock (RIDs) Task. We have conducted a novel translational study to explore the neural correlates of aversion resistant alcohol addiction using a paradigm, which adds an aversive component to the RID task. In this study, the participants (light and heavy drinkers) were able to earn points for real alcohol and food rewards at the risk of receiving a small electric shock. Compared with light drinkers, heavy drinkers attempted to earn more aversion-paired alcohol points. Fronto-striatal circuitry, including the medial prefrontal cortex, anterior insula, and striatum, was more active in this group when viewing threat-predictive alcohol cues. Heavy drinkers had increased connectivity between the anterior insula and the nucleus accumbens. Greater connectivity was associated with more attempts to earn aversion-paired alcohol points and self-reported compulsive alcohol use scores. Higher activation of fronto-striatal circuitry in heavy drinkers may be associated with compulsive alcohol seeking (Grodin et al., 2018). We are currently revising the follow up study that would compare the above results with a more general salient reward such as money in heavy alcohol drinkers in contrast to light drinkers. This study has the potential of unravelling whether the failure to avoid actions with negative consequences are specific to alcohol or in general to any reward. 3. fMRI Studies of Stress In a collaborative study with Dr. Lohoffs CGET we have implemented an fMRI fear extinction task. The primary goal of this study is to evaluate the role and interaction of (epi)genetic factors, early life stress (ELS) exposure, and alcohol use disorder (AUD) on neuronal mechanisms of fear conditioning and extinction. This cross-sectional, case-control study found significantly reduced amygdala activation during fear conditioning and fear renewal in individuals with alcohol dependence compared to healthy controls. Decreased amygdala activation during fear conditioning was significantly associated with alcohol dependence-related clinical measures, including alcohol dependence severity, depressive symptoms, trait anxiety, and perceived stress. (Muench et al., 2019, submitted) 4. Experimental fMRI Studies and Treatments a. Effect of Pioglitazone on reward response in patients with alcoholism. We have evaluated the role of pioglitazone, an anti-inflammatory drug, on the neural processes associated with craving related reward response in a monetary incentive delay task. This study was done in collaboration with Dr. Nancy Diazgranados. The effects were studied in inpatients that received the pioglitazone treatment and a control group of inpatients that received a placebo. The grouping was double blinded and randomly assigned. The placebo group showed significantly greater activation in the posterior cingulate area during the anticipation phase, and activation in the precuneus, sensory motor area and precentral gyrus during reward specific anticipation compared to the treatment group. (Data presented at 2019 RSA conference)

1。认知功能的研究 一个。 FMRI关于社会情感处理的研究。这项研究的目的部分是检查与AUD相关的社会情感处理差异。我们已经在科学会议上进行并介绍了临时分析。我们发现，与对照组相比，患有AUD的个体是通过腹侧前扣带回和记忆记忆通过海马在与社会情感刺激旁边的酒精分散剂一起介绍时通过海马的参与而进行的。在眶额皮质中也看到了类似的作用。在与道德刺激旁边的酒精分散因子呈现期间，AUD的个体参与道德加工区域（后扣带回，颞叶交界处和额头）。在杏仁核，内侧前额叶皮层和颞极区域中看到的类似作用。这些影响在饮酒量更大的个体中更为明显。这些结果表明，酒精提示干扰认知和情感处理。 b。 在即将进行的一项研究中，将测试折现率与饮酒者与轻饮酒者之间决策的折现率和神经过程的差异。当直接和未来的奖励涉及酒精或金钱时，这项研究将有助于理解这些差异，并且当这些奖励提示在负面和积极的后果刺激的背景下提出时。这项研究的结果可能会提供有关使用神经反馈或经颅磁刺激者等方法做出较少冲动选择的潜在治疗目标的信息。 c。 目前，正在使用反应任务（IIRT）评估酗酒者认知过程和运动过程的相互作用。这项研究将通过评估与酗酒者的抑制反应以及与健康对照参与者相比的行为和神经反应来测试这种相互作用。 d。 在选择是否向慈善事业捐款时，我们正在确定和研究决策的神经相关性。先前的研究发现，慈善决策与通过腹侧前额叶皮层（VMPFC;例如Hare等，2010; Izuma等，2010; izuma et al。，2010; tusche et al an al t and and and and and and and and and and an al t al。上述区域已与AUD有关，我们进行这项研究的目标是，此类fMRI任务是否会在AUD患者作为生物标志物的决策过程中提供进一步的粒度。 2。fMRI动机研究 一个。通过与Falk Lohoff博士的临床基因组学和实验治疗（CGET）合作，我们分析了货币激励延迟（MID）任务数据，以调查与精神疾病有关的许多遗传变异之间是否存在任何关联，这在奖励饮酒患者的奖励处理过程中，在奖励过程中，伴随着精神疾病的激活和激活。 我。 常见的MDD和AUD风险变体。 AUD通常与其他精神疾病（例如重度抑郁症（MDD））合并。 TMEM161B-MEF2C区域（RS10514299）中的一个基因座已被确定为MDD的风险变体。另一方面，以前的报告表明，AD和MDD中的奖励处理中断。我们研究了在AUD的奖励/损失期间，RS10514299与纹状体大胆响应之间的关联。与健康对照组相比，携带T等位基因的患者在预期高奖励和损失（高和低）避免的高度奖励和损失（高和低）期间表现出明显更大的壳质激活，并且与健康对照组相比，预期奖励低的趋势。 （Muench等人2018） ii。 COMT的遗传变异预测AUD中的奖励处理。我们还与Lohoffs Broup博士合作，以确定AUD和HCS个体中COMT的遗传变异是否与奖励处理过程中的差异纹状体（尾状，pe骨，壳核）相关。在这项研究中，与对照组相比，在奖励预期期间，AUD患者在奖励预期期间表现出明显更大的激活。在回避预期损失期间，AUD组在尾状和伏隔核中还显示出明显更大的激活。与对照组相比，携带次要T型高位基因的AUD的个体在奖励预期期间表现出明显更大的大胆反应。对于HCS，这种反应朝相反的方向。这一发现表明，使用奖励预期响应作为COMT基因变种中AUD的生物标志物的可能性。 （Muench等，2018） b。强迫性和奖励激励延迟（READS）任务。我们进行了一项新颖的翻译研究，以使用范式探索抗厌恶性酒精成瘾的神经相关性，从而为RED任务增加了厌恶成分。在这项研究中，参与者（轻便饮用者）能够赢得真正的酒精和食物奖励的积分，冒着收到小电击的风险。与饮酒者相比，大量饮酒者试图赚取更多的厌恶饮酒点。在观看威胁可预测性的酒精提示时，包括内侧前额叶皮层，前岛和纹状体在内，包括内侧前额叶皮层，前岛和纹状体，在该组中更为活跃。大量饮酒者在前岛和伏隔核之间的连通性提高。更大的连通性与更多的尝试获得厌恶饮酒点和自我报告的强迫性酒精使用评分有关。较高的饮酒者额叶纹状体电路的更高激活可能与强迫性酒精相关（Grodin等，2018）。我们目前正在修改后续研究，将上述结果与更普遍的显着奖励（例如，与饮酒者的饮酒者相比之下）进行比较。这项研究的潜力是阐明是否避免对不负面后果的行为是针对酒精或通常奖励的。 3。压力的fMRI研究 在与Lohoffs Cget博士的合作研究中，我们实施了fMRI恐惧灭绝任务。这项研究的主要目的是评估（EPI）遗传因素，早期生命应激（ELS）暴露以及酒精使用障碍（AUD）在恐惧调节和灭绝的神经元机制上的作用和相互作用。这项横截面的病例对照研究发现，与健康对照组相比，在恐惧调节过程中，恐惧调节过程中杏仁核的激活显着降低，而害怕更新。恐惧调节期间杏仁核激活的减少与酒精依赖相关的临床指标显着相关，包括酒精依赖性严重程度，抑郁症状，性状焦虑和感知的压力。 （Muench等，2019，提交） 4。实验功能磁共振成像研究和治疗 一个。 吡格列酮对酒精中毒患者奖励反应的影响。我们已经评估了一种抗炎药Pioglitazone在货币激励延迟任务中与渴望相关奖励反应相关的神经过程中的作用。这项研究是与Nancy Diazgranados博士合作完成的。在接受吡格列酮治疗的住院患者和接受安慰剂的住院患者的对照组中研究了这些效果。分组是双盲的，并随机分配。在预期阶段，安慰剂组在后扣带回区域的激活明显更大，与治疗组相比，在奖励特定预期期间，前扣带回，感觉运动区域和前中心的激活。 （在2019年RSA会议上提供的数据）