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

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.