TEST-RETEST RELIABILITY OF PUTATIVE FMRI ENDOPHENOTYPES FOR SUBSTANCE ABUSE RISK

药物滥用风险推定 FMRI 内表型的重测可靠性

• 批准号: 9035991
• 负责人: Andrey P. Anokhin
• 金额: $ 20.59万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9035991
• 关键词: Affect; Asses; Attention deficit hyperactivity disorder; Behavior; Behavior Control; Binding; Brain; Characteristics; Clinical; Data; Dependence; Drug usage; Equation; Etiology; Experimental Designs; Exploratory/Developmental Grant; Foundations; Functional Magnetic Resonance Imaging; Future; Genetic; Genetic Risk; Genetic study; Goals; Heritability; Image; Individual; Individual Differences; Informal Social Control; Investigation; Investments; Knowledge; Linear Models; MRI Scans; Measures; Mediating; Modeling; Monozygotic twins; Morphologic artifacts; Motion; Neurosciences; Pathway interactions; Phenotype; Predisposition; Procedures; Psychopathology; Resources; Risk; Role; Sampling; Self-control as a personality trait; Shapes; Signal Transduction; Solid; Substance abuse problem; Testing; Time; Twin Multiple Birth; addiction; base; blood oxygen level dependent; blood oxygenation level dependent response; case control; design; developmental genetics; endophenotype; frontal lobe; hemodynamics; imaging biomarker; independent component analysis; indexing; neurobehavioral; neurobiological mechanism; neuroimaging; neuromechanism; public health relevance; relating to nervous system; response; response biomarker; tool; trait; transmission process; young adult

 DESCRIPTION (provided by applicant): The overall goal of this exploratory-developmental study is to identify neuroimaging markers of response inhibition with significant test-retest reliability and familial resemblance, important criteria for inclusion in a larger-scale genetic stdy of endophenotypes for addiction risk. The role of genetic factors in predisposition to addictive disorders is well documented, however, neurobiological mechanisms mediating these genetic influences are poorly understood. Converging evidence suggests that risk for addictions can be mediated by deficits in inhibitory self-regulation of behavior. Functional magnetic resonance imaging (fMRI) is an important tool for investigation of brain mechanisms and pathways underlying inhibitory control. However, a critical barrier to genetic studies of the neural mechanisms of inhibitory control is the dearth of knowledge about reliability of fMRI phenotypes. Evidence for test-retest reliability is an important prerequisite for genetic studies because only stable, trait-like individual differences can be heritable, and test-retest reliability can be viewd as the upper boundary for heritability. Since adequately powered genetic studies require large samples and thus substantial investment of time and resources, selection of imaging phenotypes for such studies should be based on solid evidence for their reliability. However, very few studies that examined test-retest reliability of brain activation in response inhibition tasks yielded inconclusive results. The proposed study will fill this gap in knowledge through a systematic investigation of long-term test-retest reliability of regional and network-level brain activation in three response inhibition tasks. Furthermore, the proposed study will provide preliminary evidence for familial transmission of fMRI phenotypes and examine a variety of factors affecting test-retest reliability. The following Specific Aims will be pursued: 1) To asses long-term test-retest reliability of regional brain activations related to response inhibition, 2) o examine the effect of experimental design, preprocessing parameters, practice effects, and data analytical approaches on test-retest reliability, and 3) To assess familial influences on fMRI measures using intrapair correlations between monozygotic (MZ) twins. Taken together, this information will allow us to identify candidate fMRI phenotypes suitable for a larger scale genetic study of the neural underpinnings of response inhibition. Since response inhibition has also been implicated as a key construct in other psychopathology (e.g. ADHD), the proposed will have a broader impact on the clinical neuroscience field.

 描述（由申请人提供）：这项探索性发展研究的总体目标是确定具有显着重测可靠性和家族相似性的反应抑制的神经影像标记，这是纳入成瘾风险内表型更大规模遗传研究的重要标准遗传因素在成瘾性疾病易感性中的作用已得到充分证明，然而，人们对介导这些遗传影响的神经生物学机制知之甚少。功能性磁共振成像（fMRI）是研究大脑机制和潜在抑制控制的重要工具，然而，抑制控制神经机制的遗传研究的一个关键障碍是缺乏。重测可靠性的证据是遗传学研究的重要先决条件，因为只有稳定的、性状状的个体差异才能遗传，而重测可靠性可以被视为遗传研究的上限。由于充分有力的遗传学研究需要大量的样本，因此需要大量的时间和资源投入，因此此类研究的成像表型的选择应基于其可靠性的可靠证据。然而，很少有研究检查大脑激活的重测可靠性。这项研究将通过对三种反应抑制任务中区域和网络水平的大脑激活的长期测试可靠性进行系统调查来填补这一知识空白。 fMRI家族传播的初步证据表型并检查影响重测可靠性的各种因素将追求以下具体目标：1）评估与反应抑制相关的区域大脑激活的长期重测可靠性，2）检查实验设计的效果。 、预处理参数、实践效果和重测可靠性的数据分析方法，以及 3) 使用同卵 (MZ) 双胞胎之间的配对内相关性来评估家族对 fMRI 测量的影响。 综合起来，这些信息将。使我们能够识别适合更大规模遗传的候选功能磁共振成像表型 反应抑制的神经基础的研究。由于反应抑制也被认为是其他精神病理学（例如多动症）的关键结构，因此该提议将对临床神经科学领域产生更广泛的影响。