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（由申请人提供）：拟议的 R03 研究的总体目标是通过整合具有高空间和时间分辨率（分别为 fMRI 和 ERP）的脑成像方法来阐明反应抑制的神经解剖学基础和神经生理学机制。该 NIDA I/START 奖项将促进申请人进入成瘾研究中的脑成像领域，使他能够生成初步数据，这些数据可用于促进在其连接遗传学和认知神经科学的研究项目中更广泛地使用成像方法，以便了解成瘾的决定因素和后果。来自关于成瘾的流行病学、遗传和认知神经科学研究的综合证据表明，一系列成瘾行为和共病外化精神病理学存在共同的遗传倾向，这反映在高度遗传的潜在特征“行为去抑制”中。然而，介导遗传影响行为抑制性自我调节的特定神经基质和机制仍然知之甚少。申请人过去和正在进行的双胞胎研究已经证明，基因对事件相关大脑电位（ERP）的额部局部成分有很强的影响，该ERP与执行/不执行任务中的冲突检测和反应抑制相关。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仍不清楚，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，我们提出对 30 对同卵双胞胎和异卵双胞胎进行功能磁共振 (fMRI) 和 ERP 联合评估。我们假设，高度遗传性的额叶 ERP 成分（N2 和 P3a）将与先前研究中涉及冲突检测和反应抑制的区域网络中的 BOLD 反应表现出显着相关性，尤其是前扣带皮层。我们进一步预计 BOLD 响应将显示显着的 MZ 孪生相关性，但不显示 DZ 孪生相关性。此外，我们将对儿茶酚胺-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 激活之间的关联进行探索性分析。这些初步数据将使我们能够结合 ERP 和 fMRI 的优势，进一步阐明反应抑制的神经底物，为 ERP 内表型提供神经解剖学验证，并支持未来 R01 项目的开发，使用“基因组成像”方法来了解成瘾脆弱性的神经遗传结构。总之，该奖项将允许申请人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项目中。 公共卫生相关性声明：物质使用障碍给社会造成的损失是巨大的。冲动控制受损被认为是成瘾的主要诱发因素。更好地了解这一主要危险因素的遗传和神经生物学基础可以促进制定更有效的预防、早期干预和治疗策略。