Using Computational Neuroimaging and Extended Smartphone Assessment to Understand the Pathways Linking Threat-Related Brain Circuits to Alcohol Misuse Across Adulthood

使用计算神经影像和扩展智能手机评估来了解威胁相关大脑回路与成年期酒精滥用之间的联系途径

• 批准号: 10584969
• 负责人: ALEXANDER JOSEPH SHACKMAN
• 金额: $ 62.76万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-10 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584969
• 关键词: Address; Adult; Alcohol Phenotype; Alcohol abuse; Alcohol consumption; Alcohols; Amygdaloid structure; Animal Model; Animals; Anterior; Anti-Anxiety Agents; Anxiety; Arousal; Behavior; Biological; Biological Psychiatry; Black, Indigenous, People of Color; Brain; Brain imaging; Brain region; Categories; Cell Nucleus; Cellular Phone; Clinical; Communities; Complex; Computer Models; Consumption; Coupling; Data; Development; Diagnosis; Dimensions; Disease; Distal; Distress; Ecological momentary assessment; Etiology; Feeling; Functional Magnetic Resonance Imaging; Goals; Human; Individual; Insula of Reil; Life; Link; Maryland; Measures; Modeling; Morbidity - disease rate; National Institute on Alcohol Abuse and Alcoholism; Negative Reinforcements; Neurobiology; Pathway interactions; Perception; Phenotype; Play; Precision therapeutics; Premature Mortality; Probability; Psychiatric Diagnosis; Psychiatry; Psychological Factors; Psychophysiology; Public Health; Research; Risk; Role; Sampling; Severities; Structure of terminal stria nuclei of preoptic region; Symptoms; Technology; Testing; Therapeutic; Uncertainty; Undifferentiated; Variant; Work; addiction; alcohol craving; alcohol misuse; brain based; clinically relevant; coping; craving; data streams; design; digital intervention; disease classification; drinking; effective therapy; excessive anxiety; imaging study; innovation; insight; interest; mortality; neural; neuroeconomics; neuroimaging; novel; pre-clinical; psychosocial; racial diversity; recruit; targeted treatment; theories; therapeutic development; tool; trait; translational model; treatment strategy

Alcohol misuse is a leading cause of human misery, morbidity, and mortality. Existing treatments are far from curative. While the roots of alcohol misuse are complex and multifactorial, Anxiety plays a key role. Models of addiction suggest that many drinkers misuse alcohol to relieve excess anxiety (‘self-medicate’). Anxiety-related states, traits, and disorders increase the odds of alcohol use and problems, and these associations are magnified among individuals who habitually use alcohol for relief. Recent research motivates the hypothesis that anxiety- fueled alcohol misuse reflects hyper-reactivity to Uncertain Threat, the prototypical trigger of anxiety. Yet several key gaps in our understanding remain: (G1) There have been no systematic, well-powered efforts to test the relevance of Uncertain Threat circuitry to dimensional variation in alcohol misuse, impeding the development of more effective or tolerable therapeutics. Prior imaging studies have largely focused on cortical regions. The relevance of subcortical regions implicated in animal models of addiction and anxiety remains unclear. (G2) Computational psychiatry recognizes 2 distinct kinds of uncertainty: Risk and Ambiguity. Which of these is more relevant to alcohol misuse remains unexplored, thwarting the development of precision treatments. (G3) Preclinical work has identified a distributed brain circuit that is sensitive to Uncertain Threat, but it remains unknown which components of this circuit are most relevant to anxiety-fueled craving and consumption in the real world. To address these questions, we will recruit a racially diverse community sample of 240 AUD+ adults, over-sampling those who use alcohol for anxiety relief. Parametric threat-anticipation paradigms will allow us to probe circuits sensitive to categorical and dimensional variation in threat uncertainty. Smartphone phenotyping will assess real-world threat exposure, threat uncertainty, anxiety, craving, and alcohol use. These data will enable us to address 3 aims. (A1) Identify the brain regions and facets of threat uncertainty most relevant to clinical variation in alcohol use, symptoms, and problems. (A2) Use smartphone technology to pinpoint modifiable factors—including alterations in perceived threat and anxiety—that trigger craving and consumption. (A3) Fusing the fMRI and smartphone data-streams will allow us to fractionate the Uncertain Threat circuit and pinpoint the components most relevant to anxiety-fueled alcohol misuse in the real world—an aim that cannot be addressed using either tool in isolation. This integrative approach promises to bridge levels of analysis and has never been applied to alcohol misuse. Summary: AUD is notoriously heterogeneous, with >2,000 unique clinical profiles. Our focus on a theoretically coherent set of dimensional measures in a diverse, clinically relevant sample promises to overcome this barrier and provide fresh insights into the underlying neurobiology. Building on well-established negative reinforcement models and a fruitful line of psychophysiological research, this study will provide a potentially transformative opportunity to identify new treatment targets; guide the development of new translational models; and inform the development of new digital interventions.

滥用酒精是人类痛苦、发病和死亡的主要原因，现有的治疗方法远非如此。 虽然滥用酒精的根源是复杂且多因素的，但焦虑模型起着关键作用。 成瘾表明许多饮酒者滥用酒精过度焦虑（“与焦虑相关的自我治疗”）。 状态、特征和疾病会增加饮酒和出现问题的几率，并且这些关联会被放大 最近的研究提出了一个假设，即习惯性使用酒精来缓解焦虑的人。 酗酒反映了对不确定威胁的过度反应，这是焦虑的典型触发因素。 我们的理解中的主要差距仍然存在：（G1）没有系统的、强有力的努力来测试 不确定威胁电路与酒精滥用维度变化的相关性，阻碍了酒精滥用的发展 更有效或可耐受的治疗方法主要集中在皮质区域。 皮层下区域与成瘾和焦虑动物模型的相关性仍不清楚（G2）。 计算精神病学认识到两种不同的不确定性：风险和模糊性，哪一个更重要。 与酒精滥用相关的因素仍未得到探索，阻碍了精准治疗的发展（G3）。 临床前工作已经确定了一个对不确定威胁敏感的分布式大脑回路，但它仍然存在 未知该回路的哪些组成部分与焦虑引发的渴望和消费最相关 为了解决这些问题，我们将招募 240 澳元以上成年人组成的种族多元化社区样本， 对那些使用酒精焦虑缓解方法的人进行过度抽样将使我们能够 探针电路对威胁不确定性的分类和维度变化敏感。 将评估现实世界的威胁暴露、威胁不确定性、焦虑、渴望和饮酒。 使我们能够实现 3 个目标 (A1) 识别与威胁不确定性最相关的大脑区域和方面。 (A2) 使用智能手机技术进行精确定位 可改变的因素——包括感知威胁和焦虑的改变——引发渴望和消费。 (A3) 融合功能磁共振成像和智能手机数据流将使我们能够分割不确定威胁回路并 找出现实世界中与焦虑引发的酒精滥用最相关的成分——这一目标无法实现 这种综合方法有望在分析和分析层面上架起桥梁。 从未应用于酒精滥用。 摘要：众所周知，澳元的种类繁多，有超过 2,000 种独特的货币。 我们的重点是在不同的、临床相关的理论上一致的维度测量集。 样本有望克服这一障碍，并为潜在的神经生物学构建提供新的见解。 本研究基于完善的负强化模型和一系列富有成效的心理生理学研究 将提供潜在的变革机会来确定新的治疗目标； 新的转化模型；并为新的数字干预措施的发展提供信息。