THE FUNCTIONAL NEUROANATOMY OF RESPONSE INHIBITION: INTEGRATING ERP AND FMRI DATA

反应抑制的功能神经解剖学：整合 ERP 和 FMRI 数据

• 批准号: 8048842
• 负责人: Andrey P. Anokhin
• 金额: $ 22.8万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8048842
• 关键词: Addictive Behavior; Address; Anterior; Architecture; Area; Award; Behavior; Brain; Brain imaging; Catecholamines; Conflict (Psychology); Data; Detection; Development; Disinhibition; Early treatment; Epidemiology; Etiology; Event; Fostering; Functional Magnetic Resonance Imaging; Future; Genetic; Genetic Polymorphism; Genomics; Goals; Image; Informal Social Control; Link; Magnetic Resonance; Mediating; Methodology; Methods; Methyltransferase Gene; National Institute of Drug Abuse; Neuroanatomy; Neurobiology; Neurosciences Research; Prevention; Psychopathology; Research; Resolution; Risk Factors; Societies; Structure; Substance Use Disorder; Time; Twin Multiple Birth; Twin Studies; Validation; addiction; blood oxygenation level dependent response; cingulate cortex; cognitive neuroscience; cost; endophenotype; imaging modality; neurogenetics; neurophysiology; programs; relating to nervous system; response; trait; treatment strategy

DESCRIPTION (provided by applicant): The overall goal of the proposed R03 study is to elucidate the neuroanatomical substrates and neurophysiological mechanisms underlying response inhibition through the integration of brain imaging methods with high spatial and temporal resolution (fMRI and ERPs, respectively). This NIDA I/START award will foster the applicant's entry to the area of brain imaging in addiction research by allowing him to generate preliminary data that can be used to facilitate more extensive use of imaging methodologies in his research program linking genetics and cognitive neuroscience in order to understand the determinants and consequences of addiction. Converging evidence from epidemiologic, genetic, and cognitive neuroscience research on addiction suggests that there is a common genetic liability to a range of addictive behaviors and comorbid externalizing psychopathology reflected in the highly heritable latent trait of "behavioral disinhibition". However, specific neural substrates and mechanisms mediating genetic influences on inhibitory self-regulation of behavior remain poorly understood. The applicant's past and ongoing twin studies have demonstrated strong genetic influences on frontally localized components of event-related brain potentials (ERPs) associated with conflict detection and response inhibition in a Go/No-Go task. However, due to the limited spatial resolution and other limitations of the ERP method, the contribution of specific neural structures and circuits to these heritable differences remains unclear, which limits the interpretation of results and impedes further research progress. To address this problem, we propose a combined functional magnetic resonance (fMRI) and ERP assessment of 30 MZ and DZ twin pairs. We hypothesize that the highly heritable frontal ERP components (N2 and P3a) will show significant correlations with BOLD responses in a network of regions implicated in conflict detection and response inhibition by previous studies, most notably the anterior cingulate cortex. We further expect that BOLD responses will show significant MZ but not DZ twin correlations. In addition, we will conduct exploratory analyses of the association between a functional polymorphism in the catecholamine-O-methyltransferase (COMT) gene and BOLD/ERP activations related to response inhibition. These preliminary data will allow us to combine the strengths of ERP and fMRI in order to further elucidate the neural substrates of response inhibition, provide a neuroanatomical validation for ERP endophenotypes, and support the development of a future R01 project using "genomic imaging" approach to understand the neurogenetic architecture of addiction vulnerability. In summary, this award will allow the applicant to incorporate brain imaging methods for the first time in his research program focused on the etiology and consequences of substance use disorders. PUBLIC HEALTH RELEVANCE STAEMENT: The costs of substance use disorders to society are enormous. Impaired impulse control has been implicated as a major predisposing risk factor for addiction. A better understanding of the genetic and neurobiological underpinnings of this major risk factor can facilitate the development of more effective prevention, early intervention, and treatment strategies.

描述(申请人提供)：建议的R03研究的总体目标是通过整合具有高空间和时间分辨率的脑成像方法(分别为fMRI和ERPs)来阐明潜在的反应抑制的神经解剖学基础和神经生理学机制。这项NIDA I/START奖将通过允许申请者生成初步数据，促进他在将遗传学和认知神经科学联系起来的研究计划中更广泛地使用成像方法，以了解成瘾的决定因素和后果，从而促进申请者进入成瘾研究的大脑成像领域。来自流行病学、遗传学和认知神经科学对成瘾的研究的综合证据表明，一系列成瘾行为存在共同的遗传易感性，并伴有外化精神病理学，反映在高度可遗传的潜在特征--“行为去抑制”上。然而，特定的神经底物和机制对行为抑制性自我调节的遗传影响仍然知之甚少。申请人过去和正在进行的双胞胎研究表明，在进行/不进行任务中，与冲突检测和反应抑制相关的事件相关脑电位(ERPs)的额部局部成分受到强烈的遗传影响。然而，由于ERP方法的空间分辨率有限和其他限制，特定的神经结构和回路对这些遗传差异的贡献尚不清楚，这限制了对结果的解释，阻碍了进一步的研究进展。为了解决这个问题，我们建议对30对MZ和DZ双胞胎进行功能磁共振(FMRI)和事件相关电位(ERP)的联合评估。我们假设，高度可遗传的额叶ERP成分(N2和P3a)将与先前研究涉及冲突检测和反应抑制的区域网络中的大胆反应显著相关，最显著的是前扣带皮质。我们进一步预计，大胆的回应将显示出显著的MZ而不是DZ孪生相关性。此外，我们还将对儿茶酚胺-O-甲基转移酶(COMT)基因的功能多态性与反应抑制相关的BOLD/ERP激活之间的关系进行探索性分析。这些初步数据将使我们能够结合ERP和fMRI的优势，以进一步阐明反应抑制的神经基础，为ERP内表型提供神经解剖学验证，并支持未来R01项目的发展，使用“基因组成像”方法来了解成瘾易感性的神经遗传结构。总而言之，该奖项将允许申请者首次将脑成像方法纳入其专注于物质使用障碍的病因和后果的研究计划。 与公共健康相关的观点：物质使用障碍给社会带来的代价是巨大的。冲动控制受损已被认为是上瘾的主要易感风险因素。更好地了解这一主要危险因素的遗传和神经生物学基础有助于制定更有效的预防、早期干预和治疗策略。