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

项目摘要/摘要 这是一项对因COVID-19疫情相关中断而损失的时间提供补充支持的提案 这对我们的科学目标的进步产生了重大影响。匹兹堡大学亲自叫停了 在大流行的两个高峰期进行了总共七个半月的研究， 参与者返回亲自访问。这份补充材料将使我们能够完成我们的纵向随访数据 对解决提案的主要假设至关重要，办法是向关键工作人员提供薪金，以支持评估， 由于大流行和随后的数据分析和手稿准备而中断的部分。 这是第二次更新的调查线特征的神经基础的认知成熟，通过 青少年时期，一个对主要精神病理学的出现非常脆弱的时期（例如，- 精神病、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），动物和死后模型显示 是回路可塑性的基础，并在青少年时期经历独特的变化。具体而言， Glu/GABA的加工，由青少年DA的增加调节，影响兴奋/抑制（E/I）平衡， 认知大脑系统，驱动皮质信噪比（SNR）增加到成年期， 认知成熟我们的中心假设是，这些NT的相对变化将增加 支持向成人水平认知过渡的神经活动的SNR。在目标1中，我们使用磁性 在7特斯拉下的共振光谱（MRS），以获得GABA和Glu以及R2'的间接测量。 测量10-30岁的人体内多巴胺（DA）的纵向变化。我们假设我们将观察到- Glu和DA测量值增加，GABA增加，导致DA*Glu/GABA比值降低 前额和皮层下区域。在目标2中，我们描述了与认知相关的SNR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 使用静息状态和结构性白色物质连接对脑连接的水平影响。我们假设 NT系统的变化将与更大的网络集成和 整个青春期的皮质-皮质下连接。我们还将评估与COVID相关的感知压力， 作为协变量控制对我们数据的可能影响。总之，这些发现有助于阐明 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， 规范性神经认知发展的临床基础，对于识别异常发育的脆弱性至关重要， 会导致精神病理学的症状。

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.