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

青春期认知系统专业化可塑性背后的大脑机制

• 批准号: 9396071
• 负责人: BEATRIZ LUNA
• 金额: $ 65.89万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-18 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9396071
• 关键词: Adolescence; Adolescent; Adolescent Development; Adult; Affect; Animal Model; Animals; Attenuated; Automobile Driving; Autopsy; Behavioral; Brain; Childhood; Cognition; Cognitive; Corpus striatum structure; Data; Development; Developmental Process; Diffusion; Diffusion Magnetic Resonance Imaging; Dopamine; Electroencephalography; Equilibrium; Functional Magnetic Resonance Imaging; Glutamates; Glutamine; Grant; Hippocampus (Brain); Human; Interneurons; Investigation; Iron; Lead; Learning; Magnetic Resonance Spectroscopy; Magnetoencephalography; Measurement; Measures; Mediating; Methods; Modeling; Mood Disorders; Neurobiology; Neurocognitive; Neurotransmitters; Noise; Pattern; Plasticizers; Process; Proxy; Psychopathology; Puberty; Rest; Schizophrenia; Short-Term Memory; Signal Transduction; Support System; System; Testing; Time; Tissues; To specify; Work; age related; brain abnormalities; brain circuitry; cognitive ability; cognitive development; cognitive function; cognitive system; executive function; gamma-Aminobutyric Acid; glutamatergic signaling; in vivo; indexing; innovation; insight; longitudinal design; macromolecule; magnetic resonance spectroscopic imaging; myelination; neural circuit; neurobiological mechanism; neurochemistry; neuromechanism; neurophysiology; neurotransmission; novel; relating to nervous system; sequence learning; spectrograph; white matter

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.

项目摘要/摘要 这是探究线上的第二个续订，表征了认知成熟的神经基础 青少年时期是对主要心理病理学出现的关键脆弱性的时期（例如 Phrenia，情绪障碍）。使用功能磁共振建立了前两个赠款的发现的基础 成像，扩散张量成像和磁脑摄影，表明在认知方面的重要专业 在青少年期间，我们现在建议探测这些潜在的机制。我们的目标 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），动物和验尸模型显示出基础电路可塑性并具有独特 青少年时期的变化。具体而言，由青少年调制的GLU/GABA处理的变化 DA的增加，影响认知大脑系统的兴奋性/抑制（E/I）平衡，驱动驱动会增加 皮质信号 - 噪声比（SNR）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 到成人水平的认知。在AIM 1中，我们将在7 Tesla处使用磁共振光谱（MRS）获得 GABA和GLU的测量以及R2'间接测量多巴胺（DA）在12-30中的体内纵向测量 一岁的孩子。 7tesla MRS提供的敏感性比3tesla具有更大的灵敏度，可显着增加 通过青少年探测变化所必需的GABA和GLU度量的准确性，这些变化尚未 要完成。我们假设我们将观察到GLU和DA的测量结果下降，并且GABA的增加 导致前额叶和皮层下区域中Da*Glu/Gaba的比率下降。在AIM 2中，我们将投资 - 探讨相对NT变化与系统级别对已知发展变化的影响 在大脑连通性中使用静止状态连接和白质完整性的度量。我们建议NT 系统变化将与更大的网络集成和皮质材料强度变化有关 通过青少年的皮质连通性。最后，在AIM 3中，我们建议表征SNR的变化 使用问题和学习问题的任务，在高阶执行功能方面改进发展的背景 工作记忆，已知通过青少年表现出重要改进的功能。一起， 这些发现与阐明不同NT系统对大脑变化的相对贡献相关 为正常神经认知发展的神经生物学基础提供新的洞察力的过程 这对于确定可能导致心理病理学异常发展的脆弱性至关重要。