Characterizing cortical signatures of inhibitory control

表征抑制控制的皮质特征

• 批准号: 10680339
• 负责人: Kelsey E Schultz
• 金额: $ 4.63万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-21 至 2025-08-20
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680339
• 关键词: Acceleration; Address; Adult; American; Anatomy; Area; Attention deficit hyperactivity disorder; Basal Ganglia; Behavioral; Brain; Child; Cognitive; Communication; Data; Development; Diagnosis; Disease; Dissociation; Electroencephalography; Electrophysiology (science); Epilepsy; Frequencies; Functional disorder; Hyperactivity; Inferior frontal gyrus; Knowledge; Methods; Modeling; Monitor; Motor; Motor Cortex; Motor output; Movement; Neurologic; Participant; Patient Monitoring; Performance; Persons; Physiological; Physiological Processes; Prefrontal Cortex; Prevalence; Process; Reaction; Research; Resistance; Resolution; Sampling; Scalp structure; Signal Transduction; Stimulant; System; Testing; Time; Treatment Protocols; cognitive control; diagnostic tool; inattention; innovation; neural; neurophysiology; neurosurgery; novel; pharmacologic; support network; treatment response; trial comparing

PROJECT SUMMARY Attention deficit hyperactivity disorder (ADHD) is a multifaceted disorder that impacts 11% of American children and persists into adulthood for roughly 1/3 of those diagnosed. The prevalence of ADHD surged by 42% between 2003 and 2011, sparking concern about the reliance on subjective diagnoses and treatment with stimulants. A comprehensive understanding of the neurophysiological basis of ADHD pathophysiology is a promising way to accelerate the development of objective diagnostic tools and expansion of treatment options. Current research suggests that disruption of the prefrontal-basal ganglia network that supports inhibitory control is a key factor in the cognitive (i.e. inattentiveness) and motoric (i.e. hyperactivity) inhibitory deficits associated with ADHD. This hypothesis is further supported by the relationship between ADHD and diminished prefrontal beta frequency activity (13-30Hz)- a putative signature of network communication between nodes of the inhibitory control system. Typical motor inhibition tasks used to study inhibitory control, such as the stop signal task, require comparing trials in which subjects moved to trials in which they withheld movement (i.e. comparing going to stopping) to identify neurological substrates of stopping. This comparison confounds physiological processes involved in motoric inhibition and the cognitive control processes preceding motoric inhibition. That is, activity underlying suppression of movement cannot be differentiated from that underlying reaction to a sudden change in environmental demands. Given the potential for these mechanisms to asymmetrically contribute to different facets of ADHD, the obfuscation of cognitive and motoric aspects of inhibition is a significant barrier to progress. To address this gap in knowledge, I developed a novel stop signal task that instructs participants to stop an on- going movement under conditions in which the stop signal is expected (planned stop) and unexpected (unplanned stop), providing an opportunity to isolate cognitive and motoric aspects of inhibition. Based on previous research, my central hypothesis is that I will observe prefrontal beta increases on unplanned stop trials in which subjects must react to a sudden change in environmental demands, reflecting cognitive aspects of inhibition, and I will observe beta increases in sensorimotor areas (but not prefrontal areas) on planned stop trials, reflecting suppression of physical movement. I will leverage my novel task to test this hypothesis by (1) using scalp electroencephalography to dissociate electrophysiological signatures associated with cognitive and motoric aspects of inhibition and (2) using intracranial electroencephalography to identify precise anatomical substrates contributing to cognitive and motoric aspects of inhibition. The information gained through this research will advance our understanding of the neurophysiological underpinnings of inhibitory control and pave the way for the potential use of EEG to diagnose ADHD and to monitor patient response to treatment regimens.

项目概要 注意力缺陷多动障碍 (ADHD) 是一种多方面的疾病，影响 11% 的美国儿童 大约 1/3 的确诊患者持续到成年。 ADHD 患病率激增 42% 2003 年至 2011 年间，引发了人们对主观诊断和治疗依赖的担忧 兴奋剂。全面了解 ADHD 病理生理学的神经生理学基础是 加速开发客观诊断工具和扩大治疗选择的有前途的方法。 目前的研究表明，支持抑制的前额叶基底神经节网络的破坏 控制是认知（即注意力不集中）和运动（即多动）抑制缺陷的关键因素 与多动症有关。 ADHD 与注意力缺陷障碍之间的关系进一步支持了这一假设。 前额叶β频率活动（13-30Hz）——节点之间网络通信的假定特征 抑制控制系统。用于研究抑制控制的典型运动抑制任务，例如停止 信号任务，需要将受试者移动的试验与他们抑制移动的试验（即， 比较停止与停止）来识别停止的神经学基础。这种比较令人困惑 参与运动抑制的生理过程和运动之前的认知控制过程 抑制。也就是说，抑制运动的潜在活动不能与潜在的活动区分开来。 对环境要求突然变化的反应。鉴于这些机制有潜力 不对称地导致多动症的不同方面，认知和运动方面的混淆 抑制是进步的重大障碍。 为了解决这一知识差距，我开发了一项新颖的停止信号任务，指示参与者停止正在进行的操作 在预期停止信号（计划停止）和意外停止信号的情况下继续运动 （计划外停止），提供了隔离抑制的认知和运动方面的机会。基于 在之前的研究中，我的中心假设是我会观察到前额叶贝塔在计划外的情况下增加 停止试验，其中受试者必须对环境需求的突然变化做出反应，反映 抑制的认知方面，我会观察到感觉运动区域的β增加（但不是 前额区域）进行计划的停止试验，反映了身体运动的抑制。我将利用我的 通过（1）使用头皮脑电图来分离电生理学来检验这一假设的新任务 与抑制的认知和运动方面相关的特征以及（2）使用颅内 脑电图识别有助于认知和运动方面的精确解剖基质 的抑制作用。通过这项研究获得的信息将加深我们对 抑制控制的神经生理学基础，并为脑电图的潜在用途铺平道路 诊断多动症并监测患者对治疗方案的反应。