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.

项目概要/摘要 工作记忆缺陷 (WM) 是儿童和青少年的一个核心跨诊断特征 精神病理学。 WM 是临床和功能结果的最强预测因素之一，但仍然存在 缺乏针对 WM 缺陷的治疗方法。 WM 在历史上被概念化为仅本地化的 背外侧前额叶皮层，而现代技术已经确立了前额叶皮层更广泛的作用 皮质（PFC）和后顶叶皮质（PPC）。有证据表明 PPC 接收直接输入 尽管其他证据表明 PPC 对传入刺激进行编码并前馈至 PFC 用于启动控制功能。我之前发现额顶叶 theta/gamma 振荡， 特别是 theta-gamma 耦合，是 WM 过程背后的神经机制。新颖的方法 非侵入性脑刺激，例如间歇性θ爆发刺激（iTBS）现在可以调节这些 不同的振荡动力学，并随后检查可能的因果或时间关系。本次获奖 将以我的初步发现为基础，将我的职业生涯从临床医生转变为独立研究员。 该以患者为中心的研究职业发展奖（K23）的目标是提供必要的 为我提供培训，以实现我的职业目标，即利用多模式神经科学方法来测量和 调节儿童和青少年神经认知缺陷背后的神经动力学 精神病理学。根据 NIMH 的优先事项，提出的培训计划将建立在我的临床基础上 神经心理学和临床研究基金会在两个方面提供全面的培训和指导 核心领域：1）神经调节和2）计算神经科学。在 2x2 阶乘双盲设计中，我们 将随机抽取 40 名左侧 DLPFC 或下侧 iTBS 存在 WM 缺陷的青少年（13-17 岁）作为样本 顶小叶（IPL）。参与者将完成主动 iTBS 会话和假 iTBS 会话。初级 结果将是 WM 需求期间的 theta-gamma 耦合，如在 WM 期间通过脑电图测量的那样 iTBS 之前和之后的空间 WM 任务。目标 1 将检查 iTBS 对 PPC 的影响 WM 的编码阶段，而目标 2 将检查 iTBS 对 PFC 对 WM 的维持阶段的影响 WM。目标 3 将利用计算神经模型来识别振荡背后的新皮质电路 调制。我的中心假设是 PFC 和 PPC 区域在执行方面具有互补的作用 WM 流程。此外，iTBS 可以调节这些区域的 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力学的框架，并设定 我的第一个 R01 阶段涉及 WM 相关的额顶振荡动力学和最佳治疗参数 青少年 WM 缺陷。这将为我的职业生涯致力于测量和 调节儿童精神病学中的振荡异常。