Neurobiological Mechanisms of Impulse Control Problems

描述（由申请人提供）：拟议的工作计划的广泛目标是调查冲动控制（外化）问题的神经生物学和认知机制。拟议中的工作建立在申请人的参与发展的层次模型的外部化。这个模型的核心思想是，一个一般的脆弱性因素，标记为外化，基础和团结的精神病理综合征，涉及反社会行为和物质依赖，以及反映冲动和侵略性的人格特质。这些问题被概念化为涉及前脑区域的缺陷，尽管研究人员才刚刚开始了解这些区域是如何工作的。最确定的外部化问题的相关性是P300事件相关电位（ERP）脑成分的振幅降低。然而，P300背后的神经机制是分布式的，并没有得到很好的理解。因此，P300振幅降低的研究还没有产生关于所涉及的神经机制的良好模型。研究人员最近开始研究与外化相关疾病相关的错误相关负性（ERN）ERP脑成分的振幅降低。据了解，ERN涉及前扣带皮层（ACC）的相对较强的激活，为研究提供了更清晰的目标。目前的ERN模型表明，这是最好的理解为ACC激活的影响，其他脑区的情况下，特别是PFC。建议的工作的目标是调查的PFC和ACC在ERN在不同的任务情况下的作用，然后调查这些关系是如何调制在个人与外化问题。主要的培训内容包括发展直接测量特定脑区的技能，以解决PFC和ACC在外化精神病理学中的关系问题。近年来已经看到了令人难以置信的增长的方法定位神经源，目前可用的技术提供了强大的可能性，推断ACC和PFC源使用ERP，磁共振成像（MRI），并结合（多模态）ERP和MRI的方法。拟议的培训活动将提供所有三种方法的培训，并由这一领域的一位主要专家提供指导。候选人还在联合时频（TF）分析方面具有很强的专业知识，这是一种新兴的电生理信号计算方法。一个重要的次要目标是将TF方法与这些神经源定位方法相结合，以创建尖端方法神经源方法。长期目标是使候选人成为一名独立的调查员，专注于精神病理学的外化，采用尖端的方法来推断所描述的神经源。

DESCRIPTION (provided by applicant): The broad aim of the proposed program of work is to investigate neurobiological and cognitive mechanisms underlying impulse control (externalizing) problems. The proposed work builds on the applicant's involvement in the development of a hierarchical model of externalizing. The core idea of this model is that a general vulnerability factor, labeled externalizing, underlies and unites psychopathological syndromes involving antisocial behavior and substance dependence, as well as personality traits reflecting impulsivity and aggression. These problems are conceptualized in terms of deficits involving anterior brain regions, although researchers are only really beginning to understand how these regions work. The most established correlate of externalizing problems is reduced amplitude of the P300 event-related potential (ERP) brain component. However, neural mechanisms underlying P300 are distributed and not well understood. Thus, studies of P300 amplitude reductions have not produced good models about the neural mechanisms involved. Researchers have recently begun investigating amplitude reductions in the error-related negativity (ERN) ERP brain component related to externalizing-related disorders. The ERN is understood to involve a relatively strong activation of the anterior cingulate cortex (ACC), providing a clearer target for study. Current models of the ERN suggest that it is best understood as an ACC activation which is influenced by other brain regions depending on the circumstances, particularly the PFC. The goal of the proposed work is to investigate the roles of the PFC and ACC during the ERN under different task circumstances, and then to investigate how these relationships are modulated in individuals with externalizing problems. The primary training components involve developing skills in direct approaches to the measurement of specific brain regions to address the question of the relationship between the PFC and ACC in externalizing psychopathology. Recent years have seen incredible growth in methods for localizing neural sources, and currently available techniques offer strong possibilities for inferring ACC and PFC sources using ERP, magnetic resonance imaging (MRI), and combined (multimodal) ERP and MRI approaches. The proposed training activities would provide training in all three approaches, with mentorship by a leading expert in this field. The candidate also brings strong expertise in joint time-frequency (TF) analysis, an emerging computational method for electrophysiological signals. An important secondary goal is to integrate TF approaches with these neural source localization methods, to create cutting-edge methods neural source methods. The long term goal is for the candidate to become an independent investigator focused on externalizing psychopathology, employing cutting-edge methods for inferring neural sources as described.