This is a revised application for an NIH K25 Mentored Quantitative Research Career Development Award entitled "Methods for dynamic causal interactions in the developing human brain". In the past decade, functional magnetic resonance imaging (fMRI) has emerged as a powerful tool for investigating human brain function. Although fMRI research has primarily focused on identifying brain regions that are activated during performance of cognitive tasks, there is growing consensus that cognitive functions emerge as a result of dynamic, context-dependent, causal interactions between multiple brain areas. Devising methods for investigating such interactions has therefore taken great significance. The human brain undergoes a protracted period of development, and understanding the maturation of causal brain dynamics underlying information processing is critical for gaining insights into brain and cognitive development. The first major goal of this proposal is to address a critical need in fMRI research by developing novel algorithms for identifying context- dependent causal interactions between distributed brain regions. To this end, we will first develop and validate novel methods based on a Multivariate Dynamical Systems (MDS) framework that overcomes major limitations of several existing methods for investigating causal interactions in the human brain. The second major goal of this proposal is to use the MDS framework to investigate dynamic causal interactions underlying sensory-motor and attention processing in adults, and their differential maturation from childhood to adulthood. The MDS-based methods I propose to develop, validate, test, and apply here will allow me to investigate these processes for the first time, leading to a more complete understanding of fundamental mechanisms underlying human brain function and development. Taken together, the proposed studies will provide important new methods for investigating distributed cortical networks underlying cognition and lead to a more complete understanding of fundamental mechanisms underlying human brain function and development. In conjunction with this research plan, a rigorous education and training program will address critical gaps in my knowledge of brain anatomy, cognitive neuroscience, cognitive psychology and developmental psychology. I will be mentored and trained by leading experts in these fields. I will also gain critical experience in designing fMRI experiments, fMRI data acquisition and analysis, and interpretation of fMRI findings in the context of brain function and development. My training program and the research project will enable me to acquire skills necessary for becoming a successful independent investigator in the fields of computational, cognitive and developmental neuroscience.

Public Health Relevance

Understanding fundamental aspects of brain function is a critical first step towards the development of more targeted treatments, therapies, and interventions for multiple psychiatric and neurological disorders which are becoming urgent public health concerns. Dynamical causal interactions across multiple brain areas play a prominent role in cognitive function. The proposed research seeks to develop and validate novel methods for estimating dynamic causal interactions between brain regions using fMRI data and apply these methods for investigating causal networks in adults underlying sensory-motor mapping and attention, and their different maturational trajectories in the developing brain.

National Institute of Health (NIH)
Mentored Quantitative Research Career Development Award (K25)
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Developmental Biology Subcommittee (CHHD)
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Freund, Lisa S
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Stanford University
Schools of Medicine
United States
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