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

1.认知功能研究 a. 我们已经评估了酒精使用障碍的认知和运动过程的潜在相互作用，目前正在使用CNIRC开发的抑制性干扰反应任务（IIRT）。使用这项任务对大约30名参与者的功能磁共振成像数据进行分析的工作正在进行中，并处于最后阶段。 B. 我们已经完成了一项关于是否为慈善事业捐款的神经相关性的研究。先前的研究发现，慈善决策与价值计算（从腹侧纹状体）与社会认知处理（如在丘脑和颞顶交界处）通过腹内侧前额叶皮层（vmPFC;例如，Hare等人，2010; Izuma等人，2010; Tusche等人，2016年）。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患者的决策过程中提供进一步的粒度作为生物标志物。29名参与者主观评价了10个慈善机构的价值，有效性和个人捐赠的机会。然后，参与者完成了一项功能性磁共振成像任务，要求他们决定向某些慈善机构捐款，考虑到捐款帮助的可能性，他们对慈善机构的个人偏好，以及捐款是否以自己的成本为代价。捐赠有帮助的概率和受试者对慈善机构的支持程度会调节PCC并离开IFG参与。有趣的是，奖励神经回路对这些变化并没有表现出类似的敏感性。慈善捐赠方案有一个主要影响（见表3 /图2）。在对比1（给予自我+基础>中性反馈）中，存在跨大脑的区域的广泛参与，包括右侧梭状回、左侧缘上回、额眼区、双侧丘脑、后扣带回（PCC）、尾状核/壳核、双侧前扣带回/IFG和双侧海马。在上级颞沟有更大的失活。在对照2（给予自我+基础>中性情景）中也发现了PCC。与选择不向慈善机构捐赠相比，决定向慈善机构捐赠与右侧IFG、左侧视觉关联区（V3）、右侧辅助运动区（SMA）和右侧上级顶叶（SPL）区域的更多参与相关。慈善特征也会影响慈善捐赠的神经基础。对比5（给予自我+基础; 100% >给予自我+基础; 30%）显示了PCC的参与。对比7（给予最喜欢>给予最不喜欢）与左IFG的更大参与和PCC的减少失活相关。我们的第二个兴趣是利用这项任务作为AUD生物标志物，当在全脑水平进行多重比较时，与健康对照相比没有显著差异。(Fede等，（正在编写中） 2.应激的fMRI研究 a.在与Lohoffs 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，早期生活压力（ELS）暴露和酒精使用障碍（AUD）对恐惧条件反射和消退的神经元机制的作用和相互作用。这项横断面病例对照研究发现，与健康对照组相比，酒精依赖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。在恐惧条件反射过程中杏仁核激活的减少与酒精依赖相关的临床指标显著相关，包括酒精依赖的严重程度、抑郁症状、特质焦虑和感知压力。（Muench等人，2019年度） B.表观基因组学研究。我们还与Lohoffs博士实验室合作进行了DNA甲基化表观基因组关联研究（EWAS）。本研究确定了与AUD相关的新的表观遗传学探针，如生长停滞特异性5基因（GAS 5）。使用外周皮质醇水平和神经影像学范式的内表型分析表明，GAS 5网络相关探针的甲基化变异与应激表型相关。在获得恐惧的功能性MRI中，在左侧杏仁核中观察到显著的关联，并且左侧和右侧杏仁核与可能与AUD相关的DNA甲基化变异。这项研究的结果表明，DNA甲基化的变化，响应酒精暴露可能介导改变大脑活动模式，通过改变HPA轴的活动和压力敏感性。海马体积也与AUD相关的表观遗传变异相关。（Lohoff等人，2020年）

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)