Brain Mechanisms Underlying Changes in Neural Oscillations through Adolescent Cognitive Maturation

青少年认知成熟导致神经振荡变化的大脑机制

• 批准号: 10675169
• 负责人: Shane McKeon
• 金额: $ 4.77万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2026-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10675169
• 关键词: Adolescence; Adolescent; Adolescent Development; Adult; Age; Animal Model; Autopsy; Biomedical Engineering; Brain; Brain region; Cells; Clinical; Cognitive; Computer Models; Coupling; Data; Data Collection; Development; Electroencephalography; Engineering; Epilepsy; Equilibrium; Event; Excision; Feedback; Glutamates; Human; Impairment; Individual; Interneurons; Knowledge; Letters; Link; Longevity; Magnetism; Measurable; Measures; Mediating; Mental Health; Methodology; Methods; Modeling; Mood Disorders; Nature; Neocortex; Neurobiology; Neurocognitive; Neurons; Neurophysiology - biologic function; Neurosciences; Neurotransmitters; Participant; Parvalbumins; Patients; Performance; Prefrontal Cortex; Process; Psychiatry; Psychopathology; Psychoses; Research Personnel; Sampling; Scanning; Short-Term Memory; Signal Transduction; Substance Use Disorder; Sum; Support System; Synapses; Techniques; Time; Work; Writing; adolescent brain development; age related; childhood epilepsy; cognitive control; cognitive development; cognitive function; cognitive neuroscience; critical period; design; executive function; gamma-Aminobutyric Acid; human model; improved; insight; magnetic resonance spectroscopic imaging; multimodal neuroimaging; multimodality; neocortical; neural; neurobiological mechanism; neuromechanism; neuropsychiatric disorder; novel; oral communication; research study; response; spectroscopic imaging; synaptic pruning; temporal measurement; ward

Project Summary Adolescence is characterized by improvements in executive function, increased plasticity, and the continued refinement of neuronal mechanisms. Importantly, it is also a time when neurobiological mechanisms are actively specializing, where strays from neurotypical development may lead to the emergence of psychopathology. To understand how atypical brain maturation may lead to neuropsychiatric disorders, typical adolescent development needs to be better understood. Previous postmortem human and animal models have shown developmental changes in the excitatory/inhibitory (E/I) balance derived from changes in the excitatory glutamate and inhibitory Gamma-Aminobutyric Acid (GABA) neurotransmitters. Decreases in the E/I balance have been shown to optimize neural systems supporting cognitive control through the stabilization of gamma oscillations, generated by parvalbumin (PV) GABAergic interneurons and measurable through electroencephalography (EEG). However, there is limited understanding of the developmental changes in the E/I balance and its impact on the neuronal mechanisms characterizing this critical period of development. Thus, this project aims to investigate the shift in the E/I balance, as implicated by developmental changes in the balance of glutamate and GABA, to characterize the neuronal underpinnings of neurotypical adolescent cognitive development. To accomplish this, we will 1) assess developmental changes in neural activity underlying working memory and its association with glutamate and GABA using multimodal neuroimaging techniques, including electroencephalography (EEG), 7T Magnetic Spectroscopic Imaging (MRSI) (Aim 1), and stereoelectroencephalography (sEEG) (Aim 2), and 2) use computational modeling to identify the micro-level neuronal underpinnings of adolescent brain development (Aim 3). During this process, the candidate will gain invaluable knowledge in technical methodologies, such as data collection, analysis, computational modeling, clinical neuroscience, and written and oral communication. This study will advance our understanding of neurotypical adolescent development, which is a critical step towards assessing impaired development that can lead to psychopathology, which predominantly emerges in adolescence (e.g., psychosis, mood disorders, substance use disorders). Altogether, this project will support the ability of the candidate to become an expert bioengineering-psychiatry researcher, integrating engineering principles and developmental cognitive neuroscience that can inform the mental health field.

项目概要 青春期的特点是执行功能的改善、可塑性的增强以及持续的 神经机制的细化。重要的是，这也是神经生物学机制活跃的时期 专业化，偏离神经典型发展可能导致精神病理学的出现。到 了解非典型大脑成熟如何导致神经精神疾病，典型的青少年 发展需要得到更好的理解。先前的人类和动物模型尸检显示 由兴奋性谷氨酸变化引起的兴奋性/抑制性 (E/I) 平衡的发育变化 和抑制性γ-氨基丁酸（GABA）神经递质。 E/I 余额减少 显示可以通过稳定伽玛振荡来优化支持认知控制的神经系统， 由小清蛋白 (PV) GABA 能中间神经元产生，可通过脑电图测量 （脑电图）。然而，人们对E/I平衡的发展变化及其影响了解有限。 关于表征这一关键发育时期的神经机制。因此，该项目旨在 研究 E/I 平衡的变化，这与平衡的发展变化有关 谷氨酸和 GABA，表征神经典型青少年认知的神经元基础 发展。为了实现这一目标，我们将 1) 评估工作中神经活动的发育变化 使用多模式神经影像技术研究记忆及其与谷氨酸和 GABA 的关联，包括 脑电图 (EEG)、7T 磁谱成像 (MRSI)（目标 1）和 立体脑电图 (sEEG)（目标 2）和 2) 使用计算模型来识别微观层面 青少年大脑发育的神经元基础（目标 3）。在此过程中，候选人将获得 技术方法方面的宝贵知识，例如数据收集、分析、计算建模、 临床神经科学，以及书面和口头交流。这项研究将加深我们对 神经典型的青少年发育，这是评估发育受损的关键一步，可以 导致精神病理学，主要出现在青春期（例如精神病、情绪障碍、 物质使用障碍）。总而言之，该项目将支持候选人成为专家的能力 生物工程精神病学研究员，整合工程原理和发展认知 可以为心理健康领域提供信息的神经科学。