Neural asynchrony underlying poor cognitive control in severe psychopathology

 描述（由申请人提供）：严重的精神障碍与认知控制能力差有关，这在未能更新对新环境的反应，有效使用短期记忆和抑制行为反应中很明显。对认知和行为的有限目标导向控制在严重精神病理学患者的日常运作中造成了可测量的困难。尽管有越来越多的证据表明，大脑皮层区域网络是认知控制功能的基础， 这些功能是未知的。拟议的工作的总体目标是更好地了解受损的上下文更新，工作记忆和反应抑制在严重的精神病理学的神经基础，通过详细说明的强度和时间的生物电振荡组成的神经网络的认知控制皮层区域。作为这个项目的一部分，我们将首先识别与认知控制相关的皮层区域和频率。通过结合使用功能性磁共振成像（fMRI）和脑电图（EEG）数据，从严重精神病理学患者、他们的一级生物学亲属和健康对照中收集数据，我们将确定大脑皮层的共同来源， 背景更新和反应抑制，并确定这些大脑区域中有助于认知控制的生物电振荡。第二，我们将测试振荡异常对其他参与者样本和其他任务（例如，工作记忆），以便完全确定支配认知控制的皮层网络的共同方面以及严重精神病理学中存在什么异常。更广泛的样本将包括患有严重情绪失调和精神病的个体。第三，我们将测试神经网络振荡与严重精神病理学的症状，行为和遗传因素的相关性。具体来说，我们将研究异常振荡活动在严重精神病理学认知控制过程中的意义，通过检查与神经病学维度、认知控制的额外行为测量、严重精神病理学风险的多基因预测因子以及与认知控制和严重精神病理学相关的候选基因的相关性。目标的完成将确定在严重的精神病理学的认知控制受损的皮层区域内的活动的时间动力学的异常。从这项工作中获得的新知识将使更有效的干预措施成为可能，这些干预措施针对严重精神障碍中的特定神经回路，并可能涉及直接操纵大脑活动。项目分析单元：分析单元包括电路、生理学、行为、基因、自我报告。

 DESCRIPTION (provided by applicant): Severe mental disorders are associated with poor cognitive control that is evident in a failure to update responses for new circumstances, effectively use short-term memory, and inhibit behavioral responses. Limited goal-oriented control over cognition and behavior creates measurable difficulties in the day-to-day functioning of people with severe psychopathology. Despite accumulating evidence of a network of cortical regions underlying cognitive control functions, the dynamic interaction of brain regions that yield these functions are unknown. The overarching goal of the proposed work is to better understand the neural basis of compromised context updating, working memory, and response inhibition in severe psychopathology by detailing the strength and timing of bioelectrical oscillations within cortical regions composing the neural network underlying cognitive control. As part of this project, we will first identify cortical regions and frequencies pertinent to cognitive control. Through combined use of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) data gathered from people with severe psychopathology, their first-degree biological relatives, and healthy controls we will identify cortical sources common to context updating and response inhibition and identify bioelectrical oscillations in these brain regions instrumental to cognitive control. Second, we will test the generalization of oscillatory abnormalities to other samples of participants and other tasks (e.g., working memory) in order to fully determine common aspects of the cortical network governing cognitive control and what abnormalities exist in severe psychopathology. The broader samples will include individuals with severe mood dysregulation and psychosis. Third, we will test neural network oscillations for relevance to symptom, behavioral, and genetic elements of severe psychopathology. Specifically, we will investigate the significance of abnormal oscillatory activity during cognitiv control in severe psychopathology by examining associations with dimensions of symptomatology, additional behavioral measures of cognitive control, and polygenic predictors of risk for severe psychopathology as well as candidate genes identified as related to cognitive control and severe psychopathology. Completion of the aims will identify abnormalities in the temporal dynamics of activity within cortical regions underlying impaired cognitive control in severe psychopathology. New knowledge gained from this work will enable more effective interventions that target specific neural circuits in severe mental disorders and may involve the direct manipulation of brain activity. Project Units of Analysis: Units of analysis include circuit, physiology, behavior, genes, self-report.