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

项目摘要/摘要 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）。基于前两赠款使用功能性磁共振的研究结果， 成像，扩散张量成像和脑磁图，表明重要的专业化认知， 在青春期的大脑系统中，我们现在建议探索这些潜在的机制。我们的目标是 表征关键神经递质（NT）的变化：γ-氨基丁酸（GABA）、谷氨酸（Glu）和 多巴胺（DA），动物和死后模型显示，基础电路可塑性和经历独特的 青春期的变化。具体来说，Glu/GABA处理的变化，由青少年调节， DA的增加，影响认知脑系统的兴奋/抑制（E/I）平衡，驱动 皮质信噪比（SNR）到成年支持认知成熟。我们的中心假设是 这些NT的相对变化将增加支持过渡的神经活动的SNR 成人水平的认知。在目标1中，我们将使用7特斯拉的磁共振光谱（MRS）来获得 GABA和Glu的测量以及多巴胺（DA）的R2'间接测量在12-30 奥尔兹。7特斯拉MRS提供了比3特斯拉更高的灵敏度， GABA和Glu测量的准确性对于探索青春期的变化是必要的， 完成任务我们假设，我们将观察到Glu和DA的测量值降低，GABA的测量值升高。 导致前额叶和皮质下区域中DA*Glu/GABA的比率降低。在目标2中，我们将投资- 量化相对NT变化与已知发育变化的系统水平效应之间的关联 使用静息状态连接和白色物质完整性的测量来研究大脑连接。我们建议NT 系统变化将与更大的网络整合和皮质激素水平的变化相关， 大脑皮层的连接最后，在目标3中，我们提出了表征 在高阶执行功能的发展改善的背景下，使用一项任务，探索学习和 工作记忆，这些功能在青春期会有重要的改善。我们一起努力， 这些发现在阐明不同NT系统对脑成熟的相对贡献方面具有相关性， 神经认知过程提供了对规范性神经认知发展的神经生物学基础的新见解 这对于识别可能导致精神病理学的异常发展的脆弱性至关重要。

Project Abstract/Summary 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). Building on the findings from the first two grants using functional Magnetic Resonance Imaging, Diffusion Tensor Imaging, and Magnetoencephalography, indicating important specialization in cogni- tive brain systems during adolescence, we now propose to probe these underlying mechanisms. We aim to characterize changes in key neurotransmitters (NT): 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 will use 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 12-30 year olds. 7Tesla MRS provides critically greater sensitivity than 3Tesla affording significant increases in the accuracy of measures of GABA and Glu necessary for probing changes through adolescence, which have yet to be done. We hypothesize that we will observe decreases 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 will inves- tigate the association between relative NT changes and systems level effects on known developmental changes in brain connectivity using resting state connectivity and measures of white matter integrity. We propose that NT systems changes will be associated with greater network integration and changes in the strength of corticosub- cortical connectivity through adolescence. Lastly, in Aim 3 we propose to characterize changes in SNR in the context of developmental improvements in higher-order executive function using a task that probes learning and working memory, functions that are known to show important improvements through adolescence. Together, these findings have relevance in elucidating the relative contributions of different NT systems to brain matura- tional processes providing novel insight into the neurobiological basis of normative neurocognitive development that is critical for identifying vulnerabilities for abnormal development that can lead to psychopathology.