Functional & Structural Connectivity in Alcohol Use Disorder

功能性

• 批准号: 10255190
• 负责人: Abdolreza Momenan
• 金额: $ 29.59万
• 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/10255190
• 关键词: Acute; Age; Alcohol consumption; Alcohols; Amygdaloid structure; Anisotropy; Anterior; Basal Ganglia; Behavioral inhibition; Biological; Blood alcohol level measurement; Brain; Compulsive Behavior; Conflict (Psychology); Corpus striatum structure; Data; Diffuse; Diffusion Magnetic Resonance Imaging; Dorsal; Failure; Female; Functional Magnetic Resonance Imaging; Fusiform gyrus; Heavy Drinking; Image; Impulsive Behavior; Impulsivity; Individual; Infusion procedures; Inpatients; Insula of Reil; Intravenous; Laboratories; Lead; Left; Manuscripts; Measures; Modeling; National Institute on Alcohol Abuse and Alcoholism; Nervousness; Neurons; Neurosciences; Neurotic Disorders; Nucleus Accumbens; Parietal; Participant; Pathway Analysis; Pattern; Personality; Personality Assessment; Personality Traits; Play; Preparation; Prevalence; Process; Radial; Research; Rest; Rodent; Role; Sampling; Scanning; Severities; Sex Differences; Stress; Structure; Testing; Withdrawal; Woman; addiction; alcohol effect; alcohol use disorder; anxious; base; binge drinking; biological sex; chronic alcohol ingestion; diffusion weighted; disorder control; drinking; drinking behavior; functional MRI scan; healthy volunteer; men; negative affect; neural circuit; neuromechanism; sex; statistics; trait impulsivity; treatment program; white matter

1. fMRI Network Analysis and Resting State Studies a. Resting state Connectivity and alcohol use disorder domains. Withdrawal/negative affect is one of the biological neurocircuitries implicated in the cycle of addiction model (Koob et al. 2010). Previous studies have indicated that amygdala connectivity and negative affect play a role in the cycle of addiction. Also, neuroticism (pessimism, nervousness, and anxiousness), which shares similar qualities with negative affect, is related to amygdala connectivity. The purpose of this study was to investigate the effect of neuroticism on the relationship between alcohol use severity and amygdala connectivity. We used the Alcohol Use Disorders Identification Test (AUDIT) to quantify alcohol use severity and the Revised NEO Personality Assessment (NEO PI-R) to quantify levels of neuroticism. The whole brain analysis showed a positive relationship between right amygdala-right temporal fusiform gyrus connectivity and AUDIT scores and a negative relationship between left amygdala-left temporal parietal junction (TPJ) connectivity and NEO neuroticism scores. The indirect effect of neuroticism was significant for the latent variable model of left amygdala connectivity with the nucleus accumbens (NAcc), posterior insula, and dorsal anterior cingulate(dACC). These results suggest that personality plays an important role in the cycle of addiction (Dean et al., 2020). b. Resting State Connectivity under acute alcohol administration. Studies conducted by Dr. Lovinger's Laboratory for Integrative Neuroscience have demonstrated a selective acute ethanol effect on external globus palidus (GPe) neurons that have a specific connectivity with the dorsal striatum (Abrahao et al.,_2016). Based on this finding and the known role of the basal ganglia in habitual, inhibitory control, and compulsive behaviors seen in addiction, we investigated the functional resting-state connectivity changes of the GPe and basal ganglia. In fact, studies in rodents have revealed that alcohol can change GPe activity by decreasing neuronal firing rates, suggesting that the GPe may have a central role in explaining impulsive behaviors and failures of inhibition that occur during binge drinking. In this study, twenty-five healthy volunteers underwent intravenous alcohol infusion to achieve a blood alcohol level of 0.08 g/dl, which is equivalent to a binge drinking episode. The resting state functional magnetic resonance imaging scan was collected prior to the infusion and at binge-level exposure. Functional connectivity analysis was used to investigate the association between alcohol-induced changes in GPe connectivity, drinking behaviors, and impulsivity traits. We found that individuals with greater number of drinks or heavy drinking days in the recent past had greater alcohol induced deficits in GPe connectivity, particularly to the striatum. Our data also indicated an association between impulsivity and alcohol-induced deficits in GPefrontal/precentral connectivity. Moreover, alcohol induced changes in GPe-amygdala circuitry suggested greater vulnerabilities to stress-related drinking in some individuals. Taken together, these findings suggest that alcohol may interact with impulsive personality traits and drinking patterns to drive alterations in GPe circuitry associated with behavioral inhibition, possibly indicating a neural mechanism by which binge drinking could lead to impulsive behaviors. (Fede et al., 2020) 2. Structural Connectivity The damage associated with chronic alcohol use on the brains white matter has been demonstrated by previous diffusion tensor imaging (DTI) research. However, there is conflicting evidence as to whether the severity of damage is influenced by an individuals biological sex. The purpose of the present study was to investigate the prevalence of sex differences in the white matter microstructure of the brains of individuals with alcohol use disorder (AUD) and healthy controls. One hundred participants with AUD (38 female) in the NIAAAs inpatient treatment program and 98 healthy control participants (52 female) underwent a diffusion weighted scan. Images collected were processed for each subject individually and voxelwise tract-based spatial statistics (TBSS) analysis was conducted to measure differences in the DTI measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) between groups. Our analyses testing for differences in group and sex revealed widespread differences between subjects with AUD and control subjects, but no interaction between group and sex. Additionally, clusters of significant group differences correlated significantly with age and heavy drinking years. Further analyses revealed that in this sample, age impacted DTI measures to a greater extent than alcohol use variables. These results bolster recent findings of similar alcohol-related microstructural damage in men and women with AUD but contradict earlier research of sex-specific structural damage.(Kisner et al., manuscript in preparation)

1. fMRI网络分析与静息态研究 a.静息状态连接和酒精使用障碍域。戒断/负面影响是成瘾模型循环中涉及的生物神经回路之一（Koob et al. 2010）。先前的研究表明，杏仁核的连通性和负面情绪在成瘾循环中发挥作用。此外，神经质（悲观、紧张和焦虑）与消极情绪有着相似的品质，与杏仁核的连通性有关。本研究旨在探讨神经质对酒精使用严重程度与杏仁核连通性之间关系的影响。我们使用酒精使用障碍识别测试（AUDIT）来量化酒精使用的严重程度，并使用修订的NEO人格评估（NEO PI-R）来量化神经质水平。全脑分析显示，右杏仁核-右颞梭状回连接与AUDIT评分呈正相关，而左杏仁核-左颞顶叶连接（TPJ）与NEO神经质评分呈负相关。神经质的间接影响是显着的潜在变量模型的左杏仁核连接与核丘脑（NAcc），后丘脑，背前扣带回（dACC）。这些结果表明，人格在成瘾循环中起着重要作用（Dean等人，2020年）。 B.急性酒精管理下的静息状态连接。由Lovinger博士的综合神经科学实验室进行的研究已经证明了对与背侧纹状体具有特定连接的外部苍白球（GPe）神经元的选择性急性乙醇作用（Abrahao等人，_ 2016年）。基于这一发现和已知的作用，基底神经节的习惯性，抑制性控制，和强迫行为中看到的成瘾，我们研究了功能的静息态连接的GPe和基底神经节的变化。事实上，对啮齿动物的研究表明，酒精可以通过降低神经元放电率来改变GPe的活性，这表明GPe可能在解释酗酒期间发生的冲动行为和抑制失败方面发挥着核心作用。在这项研究中，25名健康志愿者 接受了静脉酒精输注，以达到血液酒精水平为0.08 g/dl，相当于暴饮暴食。在输注前和暴饮暴食水平暴露时收集静息状态功能性磁共振成像扫描。功能连接分析被用来研究酒精引起的GPe连接变化，饮酒行为和冲动性状之间的关联。我们发现，在最近的过去，饮酒次数较多或饮酒量较大的个体在GPe连接方面有更大的酒精诱导缺陷，特别是纹状体。我们的数据还表明，冲动和酒精诱导的缺陷之间的关联GPEfrontal/中央前连接。此外，酒精引起的GPe-杏仁核回路的变化表明，一些人更容易受到与压力有关的饮酒的影响。总之，这些发现表明，酒精可能与冲动的人格特质和饮酒模式相互作用，以驱动与行为抑制相关的GPe电路的改变，这可能表明酗酒可能导致冲动行为的神经机制。(Fede例如，2020年） 2.结构连通性 先前的扩散张量成像（DTI）研究已经证明了慢性酒精使用对大脑白色物质的损害。然而，关于损伤的严重程度是否受个体生物学性别的影响，存在相互矛盾的证据。本研究的目的是调查酒精使用障碍（AUD）患者和健康对照者大脑白色物质显微结构的性别差异。在NIAAA住院治疗计划中，100名AUD参与者（38名女性）和98名健康对照参与者（52名女性）接受了弥散加权扫描。对每例受试者收集的图像进行单独处理，并进行基于体素的空间统计（TBSS）分析，以测量组间各向异性分数（FA）、轴向扩散率（AD）和径向扩散率（RD）的DTI测量值差异。我们的分析测试组和性别的差异显示，AUD受试者和对照受试者之间存在广泛的差异，但组和性别之间没有相互作用。此外，显著的组间差异与年龄和大量饮酒年份显著相关。进一步的分析表明，在这个样本中，年龄影响DTI措施在更大程度上比酒精使用变量。这些结果支持了最近在男性和女性AUD中发现的类似酒精相关的微结构损伤，但与早期的性别特异性结构损伤研究相矛盾。（Kisner等人，（正在编写中）