Attention-Related Neural Circuitry in Pediatric Anxiety and ADHD

小儿焦虑症和多动症中的注意力相关神经回路

• 批准号: 10561956
• 负责人: Kirsten Gilbert
• 金额: $ 78.48万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10561956
• 关键词: Affect; Age; Anxiety; Anxiety Disorders; Area; Attention; Attention deficit hyperactivity disorder; Brain; Child; Child Support; Childhood; Data; Development; Disease; EP300 gene; Electroencephalography; Event; Event-Related Potentials; Executive Dysfunction; Feedback; Fright; Functional Magnetic Resonance Imaging; Goals; High Prevalence; Impairment; Light; Link; Location; Loudness; Measures; Mental disorders; Meta-Analysis; Morbidity - disease rate; Names; Nature; Neurosciences; Noise; Play; Public Health; Reporting; Research; Research Personnel; Signal Transduction; Specificity; Stimulus; System; Techniques; Testing; Work; Youth; brain circuitry; childhood anxiety; comorbidity; computer game; design; effective therapy; executive function; experience; neural circuit; novel; peer; personalized intervention; research study; response; sound; stressor; support network; temporal measurement; therapy design; tool; treatment of anxiety disorders

Anxiety disorders are the most common form of pediatric psychiatric illness, affecting up to 30% and severely impairing up to 20% of all youth prior to age 18. Unfortunately, up to 50% of children remain symptomatic even with best available treatments, making anxiety disorders a major public health problem. To devise new treatments for anxiety disorders, more research is needed into underlying brain mechanisms. Research studying mechanisms suggests that anxiety disorders are linked to alterations in attention, including increased attention to threatening stimuli (e.g., feared objects or sounds). However, more recent research suggests these attention alterations may be due to a larger problem in which attention is increased to all stimuli (e.g., any loud noise, flash of light, etc.). This alteration in attention seems to be the opposite of ADHD, the prototypical disorder of attention in childhood and also a common childhood psychiatric disorder. In ADHD, children appear to have a generalized decrease in attention to suddenly appearing stimuli (e.g., children with ADHD might not hear their name called). Intriguingly, although anxiety and ADHD appear to demonstrate opposing attention- related problems, these disorders occur in the same child more often than expected by chance. Understanding the brain mechanisms underlying attention alterations in pediatric anxiety and ADHD is critical in designing new treatments that attempt to target or ‘correct’ problems in these brain mechanisms. In this study, we test the hypothesis that attention-related brain circuitry is overactive in anxiety disorders such that bright objects and errors elicit increased activity compared to children with no disorder. We further predict this circuitry is underactive in ADHD such that bright objects and errors elicit diminished activity increases. We hypothesize that children with both anxiety and ADHD have an intermediate level of activity (similar to children with no disorder), though less is known in this area. Finally, we predict that peer observation (a mild threat/stressor) further exacerbates the overly active attention-related brain circuitry in children with anxiety. To test these hypotheses, we use cutting-edge neuroscience tools to provide a nuanced characterization of attention-related brain circuitry in N=300 children ages 10-12 years with anxiety disorders (n=75), ADHD (n=75), both anxiety and ADHD (n=75), and no psychiatric disorder (n=75). Children play a computer game during which we measure how suddenly appearing objects capture their attention. Brain activity is measured using functional MRI, pinpointing the specific brain locations that are disrupted; and electroencephalography (EEG), providing precise timing information. We characterize attention-related brain circuitry when children are being observed by a peer versus without this stressor. This study will provide a comprehensive description of circuit-level mechanisms of altered attention in pediatric anxiety, ADHD, and co-morbid conditions, providing mechanistic targets for novel treatment design. Results could ultimately have major public health impact, by assisting in the design of new treatments for two of the most prevalent and impairing childhood psychiatric disorders.

焦虑症是儿科精神疾病最常见的形式，影响高达30%且严重 高达20%的青少年在18岁之前受损。不幸的是，高达50%的儿童即使在18岁之前仍有症状 最好的治疗方法，使焦虑症成为一个主要的公共卫生问题。设计出新的 对于焦虑症的治疗，需要对潜在的大脑机制进行更多的研究。研究 研究机制表明，焦虑症与注意力的改变有关，包括注意力增加 注意威胁刺激(例如，令人恐惧的物体或声音)。然而，最近的研究表明，这些 注意力改变可能是由于更大的问题，其中对所有刺激(例如，任何响亮的刺激)的注意力都增加了 噪音、闪光等)。这种注意力的变化似乎与典型的ADHD相反 儿童注意力障碍也是一种常见的儿童精神障碍。在ADHD中，孩子们会出现 对突然出现的刺激的注意力普遍减少(例如，ADHD儿童可能不会 听到他们的名字被呼唤)。有趣的是，尽管焦虑和多动症似乎表现出相反的注意力-- 相关问题，这些疾病偶然发生在同一个孩子身上的频率比预期的要高。理解 儿童焦虑症和多动症注意力改变的大脑机制在设计中至关重要 尝试针对或纠正这些大脑机制中的问题的新治疗方法。在这项研究中，我们测试 该假说认为焦虑症患者注意力相关的大脑回路过度活跃，从而使明亮的物体 与没有障碍的孩子相比，错误会引发更多的活动。我们进一步预测这个电路是 ADHD患者活动不足，导致明亮的物体和错误导致活动量增加。我们假设 同时患有焦虑和ADHD的儿童有中等水平的活动(类似于没有焦虑和ADHD的儿童 无序)，尽管对这一领域知之甚少。最后，我们预测同行观察(轻微的威胁/应激源) 进一步加剧了焦虑症儿童过度活跃的注意力相关脑回路。为了测试这些 假设，我们使用尖端的神经科学工具来提供与注意力相关的细微差别的特征 N=300名10-12岁患有焦虑症(n=75)、多动症(n=75)的儿童的脑电活动 ADHD(n=75)，无精神障碍(n=75)。孩子们玩电脑游戏，在游戏中我们 测量一下突然出现的物体吸引他们注意力的程度。脑活动的测量使用功能 MRI，精确定位被破坏的特定大脑位置；和脑电(EEG)，提供 精确的计时信息。我们描述了当儿童被观察时与注意力相关的大脑回路 被同龄人和没有这种压力源。这项研究将对电路级进行全面描述 儿童焦虑、多动症和共病条件下注意力改变的机制，提供机械性 新的治疗设计的目标。结果最终可能会对公共卫生产生重大影响，因为它有助于 为两种最常见和最严重的儿童精神障碍设计新的治疗方法。