Modulation of Frontoparietal Dynamics in Adolescent Working Memory Deficits

青少年工作记忆缺陷中额顶叶动态的调节

• 批准号: 10425474
• 负责人: Brian Kavanaugh
• 金额: $ 18.39万
• 依托单位: EMMA PENDLETON BRADLEY HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10425474
• 关键词: Adolescent; Area; Award; Base of the Brain; Behavioral; Cerebral cortex; Child Psychiatry; Childhood; Clinical; Clinical Research; Collection; Complex; Computer Models; Coupling; Data; Double-Blind Method; Electroencephalography; Electrophysiology (science); Feeds; Foundations; Goals; Inferior; Interneurons; Intervention; K-Series Research Career Programs; Left; Lobule; Maintenance; Measures; Memory impairment; Mentorship; Methods; Mind; Modernization; National Institute of Mental Health; Neurocognitive Deficit; Neurons; Neuropsychology; Parietal; Parietal Lobe; Participant; Pattern; Performance; Periodicity; Physiologic pulse; Prefrontal Cortex; Process; Psychopathology; Randomized; Research; Research Personnel; Role; Sampling; Scalp structure; Short-Term Memory; Signal Transduction; Stimulus; Technology; Training; Translating; base; brain magnetic resonance imaging; career; clinical predictors; cognitive control; computational neuroscience; design; executive function; functional outcomes; improved; memory process; model design; multimodality; neocortical; neural model; neuromechanism; neuroregulation; noninvasive brain stimulation; novel; novel strategies; optimal treatments; patient oriented research; primary outcome; relating to nervous system; skills

Project Summary/Abstract Deficits in working memory (WM) comprise a core, transdiagnostic feature of childhood and adolescent psychopathology. WM is one of the strongest predictors of clinical and functional outcomes, yet there remains a dearth of treatments available for WM deficits. WM was historically conceptualized as solely localized to the dorsolateral prefrontal cortex, while modern technology has established the broader role of the prefrontal cortex (PFC) and posterior parietal cortex (PPC). There is evidence to suggest that PPC receives direct input from PFC, although other evidence suggests the PPC encodes incoming stimuli and feeds forward to the PFC for the initiation of control functions. I have previously found that frontoparietal theta/gamma oscillations, particularly theta-gamma coupling, is a neural mechanism underlying WM processes. Novel approaches to non-invasive brain stimulation, such as intermittent theta burst stimulation (iTBS) can now modulate these distinct oscillatory dynamics and subsequently examine possible causal or temporal relationships. This award would build on my preliminary findings and transition my career from a clinician to an independent researcher. The objective of this Patient-Oriented Research Career Development Award (K23) is to provide the necessary training for me to obtain my career goal of utilizing a multimodal neuroscientific approach to measure and modulate the neural dynamics underlying neurocognitive deficits in childhood and adolescent psychopathology. In line with NIMH priorities, the training plan proposed will build upon my clinical neuropsychology and clinical research foundation to provide comprehensive training and mentorship in two core areas: 1) Neuromodulation and 2) Computational Neuroscience. In a 2x2 factorial double-blind design, we will randomize a sample of 40 adolescents (13-17 years) with WM deficits to iTBS at the left DLPFC or inferior parietal lobule (IPL). Participants will complete an active iTBS session and a sham iTBS session. The primary outcome will be theta-gamma coupling during WM demands, as measured via electroencephalography during a spatial WM task immediately before and after iTBS. Aim 1 will examine the effect of iTBS to the PPC on the encoding stage of WM, while Aim 2 will examine the effect of iTBS to the PFC on the maintenance stage of WM. Aim 3 will utilize computational neural modeling to identify the neocortical circuitry underlying oscillatory modulation. My central hypothesis is that the PFC and PPC regions have complimentary roles in executing WM processes. Further, iTBS can modulate theta-gamma coupling in these regions to improve behavioral performance. We will establish a framework for modulating oscillatory dynamics in child psychiatry and set the stage for my first R01 on WM-related frontoparietal oscillatory dynamics and optimal treatment parameters for adolescent WM deficits. This will provide the foundation required to dedicate my career to measuring and modulating oscillatory abnormalities in child psychiatry.

项目摘要/摘要 工作记忆的缺陷（WM）包括儿童和青少年的核心，经诊断的特征 心理病理学。 WM是临床和功能结果的最强预测指标之一，但仍然存在 缺乏可用于WM缺陷的治疗方法。 WM在历史上被概念化为仅本地化 背外侧前额叶皮层，而现代技术已经确立了前额叶的广泛作用 皮质（PFC）和后顶叶皮层（PPC）。有证据表明PPC接收直接输入 来自PFC，尽管其他证据表明PPC编码传入的刺激并将其前进到PFC 为了启动控制功能。我以前已经发现额叶theta/伽玛振荡， 特别是theta-gamma耦合，是WM过程的基础神经机制。新颖的方法 非侵入性大脑刺激，例如间歇性theta爆发刺激（ITB）现在可以调节这些 独特的振荡动力学，随后检查可能的因果关系或时间关系。这个奖项 我的职业生涯从临床医生到独立研究人员的职业生涯都基于我的初步发现和过渡。 这个面向患者的研究职业发展奖（K23）的目的是提供必要的 我的培训以获得我的职业目标，即利用多模式神经科学方法测量和 调节儿童和青少年的神经认知缺陷的基础神经动力学 心理病理学。符合NIMH优先事项，提出的培训计划将基于我的临床 神经心理学和临床研究基金会，提供两项全面的培训和指导 核心区域：1）神经调节和2）计算神经科学。在2x2阶乘双盲设计中，我们 将在左DLPFC或较低的情况下随机分组40个青少年（13-17岁）的样本（13-17年） 顶叶（IPL）。参与者将完成一个主动的ITB会话和假手册会话。主要 结果将是WM需求期间的theta-gamma耦合，如在脑电图中测量 ITB之前和之后的空间WM任务。 AIM 1将检查ITB对PPC对PPC的影响 WM的编码阶段，而AIM 2将检查ITB对PFC在维护阶段的影响 Wm。 AIM 3将利用计算神经建模来识别振荡的新皮层电路 调制。我的中心假设是PFC和PPC地区在执行 WM流程。此外，ITB可以在这些区域调节theta-gamma耦合以改善行为 表现。我们将建立一个调节儿童精神病学振荡动态的框架，并设置 我在WM相关的额叶振荡动力学和最佳治疗参数上的第一个R01的阶段 青少年WM缺陷。这将为我的职业生涯提供衡量和 调节儿童精神病学的振荡异常。