Brain Mechanisms Underlying Plasticity in the Specialization of Cognitive Systems through the Adolescent Period: Covid Supplement

青春期认知系统专业化可塑性背后的大脑机制：Covid 补充

• 批准号: 10512793
• 负责人: BEATRIZ LUNA
• 金额: $ 20.96万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-08 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10512793
• 关键词: Address; Adolescence; Adolescent; Adult; Affect; Age; Animal Model; Animals; Automobile Driving; Autopsy; Brain; COVID-19 pandemic; Cognition; Cognitive; Data; Data Analyses; Data Collection; Development; Dopamine; Equilibrium; Faculty; Glutamates; Grant; Human; Institution; Insula of Reil; Interruption; Lateral; Lead; Link; Magnetic Resonance Spectroscopy; Manuscripts; Measures; Medial; Modeling; Mood Disorders; Neurobiology; Neurocognitive; Neurotransmitters; Noise; Parents; Participant; Pattern; Persons; Prefrontal Cortex; Preparation; Process; Psychopathology; Puberty; Rest; Scanning; Schizophrenia; Signal Transduction; Slice; Stress; Structure; Suggestion; System; Thalamic structure; Time; Universities; Visit; Wages; age related; base; cingulate cortex; cognitive development; cognitive system; cohort; coronavirus disease; critical period; data acquisition; data analysis pipeline; design; follow-up; gamma-Aminobutyric Acid; imaging approach; in vivo; insight; longitudinal analysis; neuromechanism; novel; pandemic disease; perceived stress; relating to nervous system; spectroscopic imaging; symposium; virtual; white matter

Project Abstract/Summary This is a proposal for supplementary support for lost time due to disruptions related to the COVID-19 pandemic that has significantly impacted progress of our scientific aims. The University of Pittsburgh stopped all in person studies during two peaks in the pandemic for a total of seven and a half months in addition to hesitancy by participants to return to in person visits. This supplement will allow us to complete our longitudinal follow-up data critical to addressing the main hypotheses of the proposal by extending salary to critical staff to support assess- ments that were interrupted due to the pandemic and subsequent data analyses and manuscript preparation. This is the second renewal on a line of inquiry characterizing the neural basis of cognitive maturation through the adolescent period, a time of critical vulnerability to the emergence of major psychopathology (e.g., schizo- phrenia, mood disorders). Here we are characterizing changes in key neurotransmitter (NT) systems: gamma- Aminobutyric acid (GABA), glutamate (Glu), and dopamine (DA), which animal and postmortem models show underlie circuit plasticity and undergo unique changes during the adolescent period. Specifically, changes in Glu/GABA processing, modulated by adolescent increases in DA, affect the excitatory/inhibitory (E/I) balance of cognitive brain systems, driving increases in the cortical signal-to-noise ratio (SNR) into adulthood supporting cognitive maturation. Our Central Hypothesis is that the relative changes of these NTs will increase the SNR of neural activity supporting the transition to adult level cognition. In Aim 1, we are using Magnetic Resonance Spectroscopy (MRS) at 7 Tesla to obtain measures of GABA and Glu as well as R2’ indirect measures of dopamine (DA) longitudinally in vivo in 10-30 year-olds. We hypothesize that we will observe de- creases in measures of Glu and DA and increases in GABA resulting in decreases in the ratio of DA*Glu/GABA in prefrontal and subcortical regions. In Aim 2, we are characterizing changes in SNR associated with cognitive development. Lastly, in Aim 3 we are characterizing the association between relative NT changes and systems level effects on brain connectivity using resting state and structural white matter connectivity. We hypothesize that NT systems changes will be associated with greater network integration and changes in the strength of cortico-subcortical connectivity through adolescence. We will also assess COVID related perceived stress to control for possible effects on our data as a covariate. Together, these findings have relevance in elucidating the relative contributions of key NT to brain maturational processes providing novel insight into the neurobiolog- ical basis of normative neurocognitive development that is critical for identifying vulnerabilities for abnormal de- velopment that can lead to psychopathology.

项目摘要/总结 这是一项针对因 COVID-19 大流行造成的中断而损失时间的补充支持的提案 这极大地影响了我们科学目标的进展。匹兹堡大学亲自制止了一切 在两次疫情高峰期间进行了总共七个半月的研究，加上犹豫不决 参会人员亲自回国参观。该补充将使我们能够完成纵向随访数据 通过向关键员工提供工资以支持评估，对于解决该提案的主要假设至关重要 由于大流行以及随后的数据分析和稿件准备而中断的论文。 这是对认知成熟的神经基础的探究路线的第二次更新 青少年时期，是一个非常容易出现主要精神病理学（例如精神分裂症）的时期。 精神障碍、精神障碍）。在这里，我们描述了关键神经递质 (NT) 系统的变化：gamma- 动物和尸检模型显示氨基丁酸 (GABA)、谷氨酸 (Glu) 和多巴胺 (DA) 是电路可塑性的基础，并在青少年时期经历独特的变化。具体来说，变化 Glu/GABA 加工受青少年 DA 增加的调节，影响兴奋/抑制 (E/I) 平衡 认知大脑系统，推动皮质信噪比 (SNR) 的增加，为成年期提供支持 认知成熟。我们的中心假设是这些 NT 的相对变化会增加 支持向成人认知水平过渡的神经活动信噪比。在目标 1 中，我们使用 Magnetic 7 特斯拉共振光谱 (MRS) 以获得 GABA 和 Glu 以及 R2’ 间接测量值 对 10-30 岁儿童体内多巴胺 (DA) 进行纵向测量。我们假设我们将观察到 Glu 和 DA 测量值增加以及 GABA 增加，导致 DA*Glu/GABA 比率降低 在前额叶和皮质下区域。在目标 2 中，我们描述了与认知相关的 SNR 变化的特征 发展。最后，在目标 3 中，我们描述相对 NT 变化与系统之间的关联 使用静息状态和结构性白质连接性对大脑连接性的水平影响。我们假设 NT系统的变化将与更大的网络集成和强度的变化相关 整个青春期的皮质-皮质下连接。我们还将评估与新冠病毒相关的感知压力 控制作为协变量对我们的数据可能产生的影响。总之，这些发现对于阐明 关键 NT 对大脑成熟过程的相对贡献为神经生物学提供了新的见解 规范神经认知发展的基础，对于识别异常发育的脆弱性至关重要 可能导致精神病理学的发展。