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不良有关，这明显表现为未能更新对新环境的反应，有效地利用短期记忆，并抑制行为反应。对认知和行为的有限目标导向控制在患有严重精神病的人的日常运作中造成了可衡量的困难。尽管积累了认知控制功能下的皮质区域网络的证据，但大脑区域的动态相互作用 这些功能是未知的。这项拟议工作的总体目标是通过详细描述构成认知控制基础神经网络的皮质区域内生物电振荡的强度和时间，更好地了解严重精神病中受损的背景更新、工作记忆和反应抑制的神经基础。作为该项目的一部分，我们将首先确定与认知控制相关的皮质区域和频率。通过结合使用功能磁共振成像(FMRI)和脑电(EEG)数据，从患有严重精神疾病的人、他们的一级生物学亲属和健康对照中收集数据，我们将识别常见的 背景更新和反应抑制，并识别这些大脑区域中有助于认知控制的生物电振荡。其次，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)的概括性，以充分确定支配认知控制的皮质网络的共同方面，以及在严重的精神病理学中存在哪些异常。更广泛的样本将包括患有严重情绪失调和精神病的个人。第三，我们将测试神经网络振荡与严重精神病的症状、行为和遗传因素的相关性。具体地说，我们将通过检查与症状学维度、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之间的关联，来研究认知控制过程中异常振荡活动在严重精神病理学中的意义。这些目标的完成将识别严重精神病理中潜在认知控制受损的皮质区域内活动的时间动力学异常。从这项工作中获得的新知识将使针对严重精神障碍的特定神经回路的更有效干预成为可能，并可能涉及对大脑活动的直接操纵。项目分析单元：分析单元包括电路、生理、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.