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.

项目总结/文摘