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; 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（由申请人提供）：拟议的R03研究的总体目标是阐明通过与高空间和时间分辨率（分别为FMRI和ERP的高空间和时间分辨率）整合脑成像方法来抑制抑制响应的神经解剖学底物和神经生理机制。这个NIDA I/Start奖将通过允许他生成可用于促进其研究计划中更广泛地利用遗传学和认知神经科学的研究计划的初步数据来促进申请人进入成瘾研究中脑成像领域的进入，以了解成瘾的决定性和后果。从成瘾的流行病学，遗传和认知神经科学研究中融合的证据表明，在高度遗传的“行为抑制”的潜在特征中反映出了一系列成瘾行为和合并的外在心理病理学的共同遗传责任。但是，介导遗传影响行为自我调节的特定神经底物和机制对行为的抑制作用仍然很少理解。申请人的过去和正在进行的双胞胎研究表明，与事件相关的大脑电位（ERP）（ERP）的正面局部成分（与冲突检测和响应抑制相关的事件相关的大脑电位（ERP））的遗传影响很大。但是，由于ERP方法的空间分辨率有限和其他局限性，特定神经结构和电路对这些可遗传差异的贡献尚不清楚，这限制了结果的解释并阻碍了进一步的研究进展。为了解决这个问题，我们提出了30 MZ和DZ双对的联合功能磁共振（fMRI）和ERP评估。我们假设，高度可遗传的额叶ERP成分（N2和P3A）将在与先前研究有关的区域网络中显示出与大胆的反应显着相关，最著名的是前扣带回皮层。我们进一步期望大胆的响应将显示出明显的MZ，但不会显示DZ双胞胎相关性。此外，我们还将对Catecholamine-O-甲基转移酶（COMT）基因（COMT）基因的功能多态性与与反应抑制有关的BOLD/ERP激活之间进行探索性分析。这些初步数据将使我们能够结合ERP和fMRI的优势，以进一步阐明响应抑制的神经基质，为ERP内型型提供神经解剖学验证，并支持使用“基因组成像”的方法来开发未来R01项目的方法，以理解添加性易变的神经元素。总而言之，该奖项将使申请人首次将大脑成像方法纳入其研究计划，重点是物质使用障碍的病因和后果。 公共卫生相关性：对社会的物质使用障碍的成本是巨大的。脉冲控制受损已被牵涉到成瘾的主要风险因素。更好地了解这种主要危险因素的遗传和神经生物学基础，可以促进开发更有效的预防，早期干预和治疗策略。