Psychometric and Neurobiological Mechanisms of Impulse Control Disorders

描述（由申请人提供）：涉及冲动控制缺陷的疾病，包括儿童品行障碍和注意力缺陷/多动障碍、成人反社会人格障碍和酒精/药物依赖（统称为外化障碍），会使患者衰弱，并给社会带来高昂的代价，需要进行研究来阐明此类疾病的生物学基础。由于其作为测量工具的独特优势（例如，高时间分辨率、信号频率映射、成本效益），皮层电图（EEG/ERP）记录是从神经生物学角度概念化和索引外化倾向的重要工具。拟议的研究将通过应用分析脑电图（EEG/ERP）数据的新方法来研究外化问题潜在倾向的神经处理缺陷，从而增进对外化障碍的神经生理学基础的了解。将使用两种创新的分析方法：(1) 心理测量建模方法，对于隔离 ERP 测量中最能指示外化相关处理偏差的方差非常有价值（Nelson、Patrick 和 Bernat，正在出版），以及 (2) EEG 时频 (TF) 分析，这是一种有效的工具，用于划分 ERP 信号的重叠分量，显示与外化的差异关系。感兴趣的主要 ERP 测量包括：(1) P300 的变体，一种已知作为外化倾向内表型的认知处理指数，以及 (2) 错误相关消极性 (ERN)，一种在线绩效监控的测量。作为纳尔逊等人的后续行动。 （待出版），这项拟议工作的目的是：（1）确定先前记录的 ERN 幅度减小和外化倾向之间的关系是否可以推广到从不同任务条件捕获的 ERN 测量，（2）使用 TF 信号分析和心理测量分析方法检查 ERN 和 P300 幅度减小反映与外化相关的独特或相互关联的神经缺陷的程度，以及（3）确定多元心理生理复合变量在预测方面是否可靠地优于个体 ERP 变量外化倾向。通过改进抑制去抑制的神经生理学指标的测量，这项研究有望产生改进的方法，用于识别处于去抑制精神病理学发展的生物风险的个体，并在神经影像学、神经化学和遗传学研究中定义冲动控制障碍机制的亚组。此外，这些发现将产生适合用于诊断和治疗反应研究的神经生理学目标变量。 公共卫生相关性：冲动控制障碍，包括反社会和成瘾，是严重的公共卫生问题。这项研究将利用创新的脑电图/ERP 方法来增进对此类疾病倾向背后的神经认知缺陷的理解。研究结果将改善潜在风险的大脑指标，可以作为诊断和治疗监测的目标。

DESCRIPTION (provided by applicant): Disorders involving deficient impulse-control-including child conduct disorder and attention- deficit/hyperactivity disorder, adult antisocial personality disorder, and alcohol/drug dependence (collectively known as externalizing disorders)-are debilitating for afflicted individuals and costly to society, and research is needed to clarify the biological basis of disorders of this kind. Because of its unique advantages as a measurement tool (e.g., high time-resolution; mapping of signal frequencies; cost-effectiveness), electrocortical (EEG/ERP) recording is a crucial tool in efforts to conceptualize and index externalizing-proneness neurobiologically. The proposed research will advance knowledge about the neurophysiological substrates of externalizing disorders by applying new approaches for analyzing electrocortical (EEG/ERP) data to an investigation of neural processing deficits underlying proneness to externalizing problems. Two innovative analytic approaches will be utilized: (1) psychometric modeling methods, which have been valuable for isolating variance in ERP measures most indicative of externalizing-related processing deviations (Nelson, Patrick, & Bernat, in press), and (2) EEG time-frequency (TF) analysis, an effective tool for partitioning overlapping components of the ERP signal that show differential relations with externalizing. Primary ERP measures of interest include: (1) variants of the P300, an index of cognitive processing known to function as an endophenotype of externalizing proneness, and (2) the error-related negativity (ERN), a measure of on-line performance monitoring. As a follow-up to Nelson et al. (in press), this proposed work aims: (1) to determine whether previously-documented relationships between ERN amplitude reduction and externalizing proneness generalize to ERN measures captured from differing task conditions, (2) to examine, using TF signal analysis and psychometric analytic methods, the degree to which ERN and P300 amplitude reductions reflect unique or interrelated neural deficits associated with externalizing, and (3) to determine whether multivariate psychophysiological composite variables reliably outperform individual ERP variables in predicting externalizing proneness. By refining measurement of neurophysiological indicators of disinhibition, this research promises to yield improved methods for identifying individuals at biological risk for the development of disinhibitory psychopathology, and for defining subgroups in neuroimaging, neurochemical, and genetic studies of mechanisms underlying disorders of impulse control. Further, the findings will yield neurophysiological target variables suitable for use in diagnostic and treatment-response studies. PUBLIC HEALTH RELEVANCE: Impulse control disorders, including antisociality and addictions, are serious public health problems. This research will utilize innovative new EEG/ERP methods to advance understanding of neuro-cognitive deficits underlying proneness to disorders of this kind. Findings will yield improved brain indicators of underlying risk that can serve as targets for diagnosis and treatment monitoring.