fMRI study of cognition, motivation, decision-making, reward, risk, aversion, negative emotion, arousal, craving, impulsivity, and stress in alcohol use disorder

功能磁共振成像研究酒精使用障碍中的认知、动机、决策、奖励、风险、厌恶、负面情绪、唤醒、渴望、冲动和压力

• 批准号: 10253680
• 负责人: Abdolreza Momenan
• 金额: $ 88.77万
• 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/10253680
• 关键词: Alcohol dependence; Amygdaloid structure; Anterior; Anxiety; Area; Arousal; Bilateral; Biological Markers; Brain; Case-Control Studies; Characteristics; Charities; Clinical; Cognition; Cognitive; Cross-Sectional Studies; DNA Methylation; Data; Decision Making; Effectiveness; Emotions; Epigenetic Process; Extinction (Psychology); Feedback; Foundations; Fright; Functional Magnetic Resonance Imaging; Fusiform gyrus; Genes; Genetic; Goals; Growth; Hares; Hippocampus (Brain); Hydrocortisone; Impulsivity; Individual; Insula of Reil; Left; Lobule; Manuscripts; Measures; Mediating; Motivation; Motor; Neurons; Parietal; Participant; Patients; Pattern; Peripheral; Phenotype; Prefrontal Cortex; Preparation; Probability; Process; Rewards; Risk; Role; Severities; Stress; Structure of superior temporal sulcus; Structure of supramarginal gyrus; Thalamic structure; Variant; Ventral Striatum; Visual; alcohol abuse therapy; alcohol exposure; alcohol response; alcohol use disorder; area V3; cognitive function; conditioned fear; cost; craving; depressive symptoms; early life stress; epigenetic variation; epigenome-wide association studies; epigenomics; frontal eye fields; hypothalamic-pituitary-adrenal axis; interest; methylomics; neural circuit; neural correlate; neuroimaging; novel; perceived stress; preference; putamen; relating to nervous system; response; social; trait

1. Study of cognitive functions a. We have assessed the potential interaction of cognitive and motor processes in alcohol use disorder is currently using the inhibitory interference of response task (IIRT) developed in CNIRC. Analysis of the fMRI data using this task for approximately 30 participants is on the way and in final stages. b. We have completed a study of the 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 also been implicated in AUD and our goal was whether such an fMRI task would provide further granularity in the decision making process of AUD patients as a biomarker. Twenty-nine participants subjectively rated ten charities on their value, effectiveness, and the subjects personal chance of donating. Participants then completed an fMRI task requiring them to decide to donate to certain charities given the probability of the donation helping, their personal preference for the charity, and whether the donation came at cost to themselves. Probability of a donation being helpful and how much the subject favored a charity moderated PCC and left IFG engagement. Interestingly, reward neurocircuitry did not demonstrate similar sensitivity to these variations. There was a main effect of charitable giving scenarios (see Table 3 / Figure 2). In contrast 1 (Giving Self + Foundation > Neutral Feedback), there was extensive engagement of regions across the brain including right fusiform gyrus, left supramarginal gyrus, frontal eye fields, bilateral thalamus, posterior cingulate (PCC), caudate/putamen, bilateral anterior insula/IFG, and bilateral hippocampus. There was greater deactivation in the superior temporal sulcus. The PCC was also found in contrast 2 (Giving Self + Foundation > Neutral Scenario). Decisions to donate to charity compared to choosing not to donate to charity was associated with greater engagement of right IFG, left visual association area (V3), right supplementary motor area (SMA), and right superior parietal lobule (SPL) regions. There were also effects of charity characteristics on neural underpinnings of charitable giving. Contrast 5 (Giving Self + Foundation; 100% > Giving Self + Foundation; 30%) showed engagement of the PCC. Contrast 7 (Giving Favorite > Giving Least Favorite) was associated with greater engagement of left IFG and reduced deactivation of the PCC. Our secondary interest in utilizing this task as an AUD biomarker, there were no significant differences compared to healthy controls when controlled for multiple comparisons at the whole brain level. (Fede et al., manuscript in preparation) 2. fMRI Studies of Stress a. 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) b. Epigenomic study. We also collaborated with Dr. Lohoffs Lab in their DNA methylation epigenome-wide association study (EWAS). This study identified novel epigenetic probs relevant to AUD such as Growth Arrest Specific 5 gene (GAS5). Endophenotypic analyses using peripheral cortisol levels and neuroimaging paradigms showed that methylomic variation in GAS5 network related probes were associated with stress phenotypes. During a fear acquisition functional MRI a significant associations were observed in the left amygdala, and both left and right insula with DNA methylation variation potentially associated with AUD. The results in this study suggested that DNA methylation changes in response to alcohol exposure may mediate altered brain activity patterns through alteration of HPA axis activity and stress sensitivity. There was also an association of hippocampal volume with this AUD related epigenetic variation. (Lohoff, et al., 2020)

1。认知功能的研究 一个。 我们已经评估了当前使用CNIRC中开发的响应任务（IIRT）的抑制性干扰，认知过程中认知和运动过程的潜在相互作用。使用此任务对大约30名参与者对fMRI数据进行分析正在途中和最后阶段。 b。 在选择是否向慈善事业捐款时，我们已经完成了对决策的神经相关性的研究。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。上述区域也与AUD有关，我们的目标是这样的fMRI任务是否会在AUD患者作为生物标志物的决策过程中进一步提供粒度。 29名参与者主观将十个慈善机构评为其价值，有效性和个人捐赠的机会。然后，参与者完成了一项功能磁共振成像的任务，要求他们决定捐赠帮助的可能性，对慈善机构的个人喜好以及捐赠是否应付出代价，因此决定向某些慈善机构捐款。捐赠有用的概率以及该主题对慈善机构主持的PCC和IFG参与度有多支持。有趣的是，奖励神经记录并未表现出对这些变化的相似敏感性。慈善捐赠方案的主要影响（请参见表3 /图2）。 In contrast 1 (Giving Self + Foundation > Neutral Feedback), there was extensive engagement of regions across the brain including right fusiform gyrus, left supramarginal gyrus, frontal eye fields, bilateral thalamus, posterior cingulate (PCC), caudate/putamen, bilateral anterior insula/IFG, and bilateral hippocampus.上颞沟中有更大的失活。在对比2中也发现了PCC（给出自我 +基础>中性场景）。与选择不向慈善机构捐款相比，捐赠给慈善机构的决定与右IFG，左视觉关联面积（V3），右补充运动区（SMA）和右上角顶叶（SPL）区域的更多参与有关。慈善特征对慈善捐赠的神经基础也有影响。对比5（给出自我 +基础； 100％>给出自我 +基础； 30％）显示了PCC的参与度。对比7（最喜欢的>最不喜欢的人）与左IFG的更多参与度和PCC停用减少有关。我们将此任务用作AUD生物标志物的次要兴趣，与健康对照组相比，在整个大脑级别进行多次比较时，没有显着差异。 （Fede等人，准备中的手稿） 2。压力研究 一个。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） b。表观基因组研究。我们还与Lohoffs Lab博士在其DNA甲基化表观基因组协会研究（EWAS）中合作。这项研究确定了与AUD相关的新型表观遗传探针，例如生长阻止特异性5基因（GAS5）。使用外周皮质醇水平和神经成像范例进行内型分析表明，GAS5网络相关探针的甲基甲基组变异与应激表型有关。在恐惧获取功能MRI期间，在左杏仁核中观察到显着的关联，并且左右岛都具有与AUD相关的DNA甲基化变异。这项研究的结果表明，DNA甲基化对酒精暴露的反应变化可能会通过改变HPA轴活动和应力敏感性来介导大脑活性的改变。海马体积与此AUD相关的表观遗传变异也有关联。 （Lohoff等，2020）