Characterizing cortical signatures of inhibitory control

项目摘要 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 并且大约1/3的被诊断者会持续到成年。多动症的患病率激增了42% 在2003年至2011年期间，引发了对主观诊断和治疗的依赖的担忧， 兴奋剂全面了解ADHD病理生理学的神经生理学基础， 这是一个有前途的方法，可以加速客观诊断工具的开发和扩大治疗选择。 目前的研究表明，破坏支持抑制性脑损伤的前额叶-基底神经节网络， 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ADHD有关。这一假设得到了ADHD和减少的 前额叶β频率活动（13- 30 Hz）-一个假定的网络通信之间的节点， 抑制控制系统。典型的运动抑制任务用于研究抑制控制，如停止 信号任务，需要比较受试者移动的试验与他们保留运动的试验（即， 比较将要停止）以识别停止的神经学基质。这种比较混淆了 参与运动抑制的生理过程和运动抑制之前的认知控制过程 抑制作用也就是说，运动抑制的潜在活动不能与运动抑制的潜在活动区分开。 对环境需求突然变化的反应。鉴于这些机制有可能 不对称有助于ADHD的不同方面，认知和运动方面的混淆， 抑制是进步的重要障碍。 为了解决这一知识差距，我开发了一个新的停止信号任务，指导参与者停止一个- 在预期停车信号（计划停车）和非预期停车信号的条件下进行运动 （计划外停止），提供了一个机会，以隔离认知和运动方面的抑制。基于 以前的研究，我的中心假设是，我会观察到前额叶β增加计划外 停止受试者必须对环境需求的突然变化做出反应的试验， 抑制的认知方面，我会观察感觉运动区的β增加（但不是 前额叶区）的计划停止试验，反映了身体运动的抑制。我会利用我的 一个新的任务来验证这一假设，通过（1）使用头皮脑电图分离电生理 与抑制的认知和运动方面相关的特征和（2）使用颅内 脑电图，以确定有助于认知和运动方面的精确解剖基质 抑制。通过这项研究获得的信息将促进我们对 抑制控制的神经生理学基础，并为EEG的潜在用途铺平了道路， 诊断ADHD并监测患者对治疗方案的反应。

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.