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.认知功能研究 A.我们已经使用CNIRC开发的反应任务抑制干扰(IIRT)评估了酒精使用障碍中认知和运动过程的潜在相互作用。使用这项任务对大约30名参与者的功能磁共振数据进行分析正在进行中，并已进入最后阶段。 我们已经完成了一项关于在做出是否向慈善事业捐款的选择时做出决策的神经关联的研究。以前的研究发现，慈善决策与价值计算(来自腹侧纹状体)和社会认知加工(如在脑岛和颞顶交界处)通过腹内侧额叶皮质(vmPFC；例如，Hare等人，2010；Izuma等人，2010；Tusche等人，2016)的整合有关。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患者的决策过程中作为生物标志物提供进一步的粒度。29名参与者根据十个慈善机构的价值、效果和受试者的个人捐赠机会对其进行主观评分。然后，参与者完成了一项fMRI任务，要求他们决定向某些慈善机构捐款，考虑到捐款的可能性，他们对慈善机构的个人偏好，以及捐款是否对他们自己有成本。捐赠有帮助的可能性以及受试者对慈善机构的支持程度主持了PCC，并离开了IFG参与度。有趣的是，奖赏神经回路并没有表现出对这些变化的类似敏感性。慈善捐赠情景有一个主要影响(见表3/图2)。在对比1(给予Self+Foundation和GT；中性反馈)中，大脑的各个区域广泛参与，包括右侧梭形回、左侧边缘上回、额眼视野、双侧丘脑、后扣带(PCC)、尾状/壳核、双侧前岛/IFG和双侧海马。在颞叶上沟有较大的失活。在对照2(给予自我+基础&>中性情景)中也发现了PCC。向慈善机构捐款的决定与不向慈善机构捐款相比，与右侧IFG、左侧视觉关联区(V3)、右侧辅助运动区(SMA)和右侧顶上小叶(SPL)区域的参与程度更高相关。慈善特征对慈善捐赠的神经基础也有影响。对比5(给予自我+基础；100%和GT；给予自我+基础；30%)显示对PCC的投入。对比7(给予最喜欢的；给予最不喜欢的)与左侧IFG的更多参与和更少的PCC去激活有关。我们对将这项任务作为AUD生物标记物的次要兴趣是，当在整个大脑水平进行多次比较时，与健康对照组相比没有显著差异。(Fede等人，手稿正在准备中) 2.应激的fMRI研究 A.在与Lohoff CGET博士的一项合作研究中，我们实施了一项fMRI恐惧消退任务。本研究的主要目的是评估(EPI)遗传因素、早期生活应激(ELS)暴露和酒精使用障碍(AUD)在恐惧条件化和消退的神经元机制中的作用和交互作用。这项横断面的病例对照研究发现，与健康对照组相比，酒精依赖患者在恐惧条件反射和恐惧更新过程中杏仁核的激活显著减少。恐惧条件反射期间杏仁核激活减少与酒精依赖相关的临床指标显著相关，包括酒精依赖严重程度、抑郁症状、特质焦虑和感知到的压力。(穆安奇等人，2019年) B.表观基因组学研究。我们还与Lohoff Lab博士合作进行了DNA甲基化表观基因组关联研究(Ewas)。这项研究发现了与AUD相关的新的表观遗传学探针，如生长停滞特异5基因(Gas5)。使用外周皮质醇水平和神经成像范式进行的内分泌表型分析表明，Gas5网络相关探针中的甲基化变异与应激表型有关。在恐惧习得功能磁共振成像中，观察到左侧杏仁核以及左右脑岛的DNA甲基化变异与AUD潜在相关。这项研究的结果表明，酒精暴露后DNA甲基化的变化可能通过改变HPA轴的活性和应激敏感性来调节脑活动模式的改变。海马体体积与AUD相关的表观遗传变异也有关联。(罗霍夫等人，2020)