CRCNS Research Proposal: Modeling Human Brain Development as a Dynamic Multi-Scale Network Optimization Process

在近二十年的时间里（从出生到成年早期），人类大脑在遗传、环境和经验因素的驱动下经历了深刻的变化。这些变化是成熟过程的一部分，导致神经回路的最佳组织，支持复杂的行为和认知过程，并促进终身学习。关于发育中的大脑回路是如何形成最佳组织的基本问题仍然存在。具体来说，潜在的生物物理机制——这一过程的间隔驱动因素在人类大脑的宏观尺度上还没有完全被理解。这在一定程度上是由于某些发育时期的复杂性，如青春期，在此期间，内源性和外源性因素的组合导致了难以追踪的部分独特生理变化的雪崩。利用近12000名青少年多年来收集的神经成像数据，先进的计算工具和工程原理，这个项目的总体目标是了解大脑内部机制如何控制其功能回路，以最佳地支持认知功能。随着大脑与年龄的联系越来越紧密，研究活动旨在量化这些机制及其内在变化，并将这些变化映射到认知处理的基本方面。本研究旨在转变对青春期独特复杂发育时期人类大脑回路优化的机制理解。为此，它将整合历史上庞大的纵向神经成像数据集，以及来自网络科学和计算机科学的新工具，以及控制理论原理。主要假设是，大脑的拓扑优化部分是由内部控制过程驱动的，该过程对网络拓扑和动态具有可量化的、随年龄变化的影响。因此，神经成熟导致简约的网络拓扑结构，使信息处理效率最大化，同时也使网络的可控性最优化，这两者都体现在认知加工的效率和灵活性上。这个项目的发现可能会对理解成人大脑回路出现的机制原理以及青春期对其发展的影响产生变革性的影响。它们还可能为改善患病或非典型发育大脑的认知结果的靶向治疗的发展提供重要见解。考虑到跨学科和高度计算活动，该项目还涉及神经科学研究界使用的重要工具开发。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Over a period of almost two decades (from birth to young adulthood), the human brain undergoes profound changes, driven by genetic, environmental and experiential factors. These changes are part of a maturation process that leads to optimally organized neural circuits that support complex behaviors and cognitive processes, and facilitate learning across the lifespan. Fundamental questions remain about how developing brain circuits become optimally organized. Specifically, the underlying biophysical mechanisms -- the interval drivers of this process are incompletely understood at the macroscale of the human brain. This is in part due to the complexity of some developmental periods, such as adolescence, during which a constellation of endogenous and exogenous factors contribute to an avalanche of partially unique physiological changes that are difficult to track. Using neuroimaging data collected over years of development from almost 12,000 adolescents, advanced computational tools and engineering principles, the overarching goal of this project is to understand how internal mechanisms in the brain control its functional circuits to optimally support cognitive function. Research activities aim to quantify these mechanisms and their inherent changes, as the brain becomes increasingly optimally connected with age, and to map these changes onto fundamental aspects of cognitive processing.This research aims to transform mechanistic understanding of the optimization of human brain circuits during the uniquely complex developmental period of adolescence. For this purpose, it will integrate a historically large, longitudinal neuroimaging dataset with novel tools from network science and computer science, and principles of control theory. The primary hypothesis is that the brain’s topological optimization is partly driven by an internal control process, which has a quantifiable, age-varying impact on network topology and dynamics. Thus, neural maturation leads to parsimonious network topologies that maximize efficiency of information processing but also optimal network controllability, both of which are reflected on the efficiency and flexibility of cognitive processing. Findings from this project may have a transformative impact on the understanding of mechanistic principles underlying the emergence of the adult brain circuitry, and the impact of adolescence on its development. They may also provide critical insights towards the development of targeted therapies for improving cognitive outcomes in the diseased or atypically developing brain. Given cross-disciplinary and highly computational activities, this project also involves significant tool development for use by the neuroscience research community.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.