The role of prefrontal sulcal morphology and brain network architecture in cognitive development

项目摘要 人类大脑的一个显著特征是皮层中的许多褶皱（沟）。据估计，60-70%的 隐藏在脑沟深处沟在子宫中出现的时间不同： 早期（原发性）被假设为受到更严格的遗传控制，因此在位置上更相似， 比那些发展较晚的人（第三代）。尽管现代认知神经科学 由于历史和方法的原因，在很大程度上忽视了这些后来发展的沟，第三纪的模式 理论上认为沟具有功能性意义（Sanides，1964）。在阐述这一观点时，我们认为， 发育过程中脑沟的加深使皮层区域更紧密地结合在一起，这使布线长度最小化， 提高局部神经信号的效率，这反过来又有助于改善认知功能。 这个R21建议的中心假设是，联合皮层中三级沟的发育 对功能性大脑结构和高级认知发展的影响。我们建议测试 这一假说首次聚焦于长期被忽视的外侧前额叶皮层（latPFC）第三脑沟， 一个与推理等高级认知能力有关的大脑区域。探索功能性 这些latPFC沟的重要性，我们建议，沟解剖， 推理能力和个体参与者的功能性大脑结构。为此，我们将利用 现有的148名年龄在6-20岁的参与者的多模态纵向数据集，包括解剖和功能 核磁共振和行为测量。在目标1a中，每个大脑半球的所有latPFC第三沟 由于识别脑沟现代自动化方法不包括三级脑沟，因此将人工定义个体。 目标1b是开发一种自动化方法，以识别我们将与患者自由共享的所有latPFC三级沟。 领域一旦脑沟定义的漫长过程完成，我们将检查latPFC的特征是否 三级沟随年龄增长而发育（目标2a）。然后，我们将测试这些特征的个体差异是否有助于 解释和/或预测推理能力的差异，根据三个标准化的潜在因素来衡量 评估（目标2b）。最后，为了将大脑解剖学与大脑功能联系起来，我们将测试个体latPFC是否 第三脑沟在推理任务中充当识别功能区域的地标， 功能关系是稳定的或随着发展而变化（目标3）。 从理论上讲，我们的建议推进了将神经解剖学和功能学的发展联系起来的理论。 latPFC的特点，认知发展和测试的经典假设。从方法论上讲， 自动化工具来定义latPFC第三沟，这也可以应用于其他皮质位置在未来。 在翻译方面，如先前的研究所报告的，注意缺陷多动障碍、精神分裂症和双相情感障碍患者的latPFC脑沟异常 疾病，但没有考虑三级沟或检查发育轨迹，拟议的研究将 为未来研究脑沟解剖在神经发育障碍中的作用奠定基础。

PROJECT SUMMARY A distinctive feature of the human brain is the many folds (sulci) in the cortex. Estimates are that 60-70% of the cortex is hidden in sulcal depths. Sulci appear at different time periods in the womb: those that appear early (primary) are hypothesized to be under tighter genetic control, and therefore more similar in location and shape across people, than those that develop later (tertiary). Although modern cognitive neuroscience has largely overlooked these later-developing sulci, for historical and methodological reasons, patterns of tertiary sulci are theorized to have functional significance (Sanides, 1964). Elaborating on this idea, we theorize that sulcal deepening during development pulls cortical regions closer together, which minimizes wiring length and increases the efficiency of local neural signals, which in turn could contribute to improved cognitive functioning. The central hypothesis of this R21 proposal is that the development of tertiary sulci in association cortices has consequences for the development of functional brain architecture and high-level cognition. We propose to test this hypothesis for the first time, focusing on the long overlooked tertiary sulci in lateral prefrontal cortex (latPFC), a brain region implicated in higher-level cognitive capacities such as reasoning. To explore the functional significance of these latPFC sulci, we propose to characterize the relationships between sulcal anatomy, reasoning ability, and functional brain architecture in individual participants. To this end, we will leverage an existing multimodal, longitudinal dataset of 148 participants ages 6-20 that includes anatomical and functional MRI and behavioral measures. In Aim 1a, all latPFC tertiary sulci in both hemispheres of the brain in each individual will be manually defined, as modern automated methods to identify sulci do not include tertiary sulci. Aim 1b is to develop an automated approach to identify all latPFC tertiary sulci that we will share freely with the field. Once the lengthy process of sulcal definition is complete, we will examine whether features of latPFC tertiary sulci develop with age (Aim 2a). We will then test whether individual differences in these features helps to explain and/or predict differences in reasoning ability, measured as a latent factor based on three standardized assessments (Aim 2b). Finally, to relate brain anatomy with brain function, we will test whether individual latPFC tertiary sulci serve as landmarks identifying functional regions during a reasoning task, and whether sulcal- functional relationships are stable or change over development (Aim 3). Theoretically, our proposal advances theories linking the development of neuroanatomical and functional features of latPFC to cognitive development and tests a classic hypothesis. Methodologically, it should yield automated tools to define latPFC tertiary sulci, which could also be applied to other cortical locations in the future. Translationally, as previous studies reported latPFC sulcal anomalies in ADHD, schizophrenia, and bipolar disorder, but did not consider tertiary sulci or examine developmental trajectories, the proposed research will serve as a foundation for future studies of the role of sulcal anatomy in neurodevelopmental disorders.