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/摘要 这是一项补充支持因新冠肺炎疫情相关的中断而损失的时间的提案 这对我们的科学目标的进展产生了重大影响。匹兹堡大学当面阻止了所有人 在大流行的两个高峰期间进行的总共七个半月的研究，除了犹豫不决之外， 参与者返回亲临现场访问。这一补充将使我们能够完成我们的纵向跟踪数据 通过向关键工作人员发放工资以支持评估，这对于解决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手稿准备而中断的部分。 这是对认知成熟神经基础研究的第二次更新。 青春期，这一时期极易出现重大精神病态(如精神分裂症--精神分裂症)。 精神错乱、情绪障碍)。在这里，我们描述了关键神经递质(NT)系统的变化：伽马- 氨基丁酸(GABA)、谷氨酸(Glu)和多巴胺(DA)，动物和身体模型显示 在青春期，电路的可塑性和经历独特的变化。具体地说，在 Glu/GABA的处理受青春期DA增加的调节，影响兴奋性/抑制性(E/I)平衡 认知大脑系统，推动皮质信噪比(SNR)增加到成年期支持 认知成熟。我们的中心假设是，这些NT的相对变化将增加 神经活动的信噪比支持向成人水平的认知过渡。在目标1中，我们使用的是Magic 在7特斯拉的共振光谱(MRS)获得GABA和Glu的测量以及R2‘间接 10-30岁儿童体内多巴胺(DA)的纵向测量。我们假设我们会观察到- 谷氨酸和多巴胺含量增加及GABA含量增加导致DA*Glu/GABA比值降低 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信噪比变化 发展。最后，在目标3中，我们描述了相对NT变化和系统之间的关联 静息状态和结构白质连通性对大脑连通性的水平效应。我们假设 NT系统的变化将与更大的网络集成和更强的 青春期期间的皮质-皮质下连接。我们还将评估与COVID相关的感知压力 控制可能对我们的数据的影响作为一个协变量。综上所述，这些发现对于阐明 关键NT在脑成熟过程中的相对贡献为神经生物学提供了新的视角-- 标准化神经认知发展的理论基础，对于识别异常痴呆的脆弱性至关重要 会导致精神病态的发育。