CAREER:Identifying Brain Anatomy and Function for Risky Behaviors in Large-Scale Imaging and Genetics Studies

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

Humans vary in their tendency to engage in behaviors that risk their own and others’ health and longevity. Such risky behaviors impose significant costs on societies, and much public spending is devoted to reducing their prevalence. This project seeks to identify the features of the human brain that underlie individual differences in the tendency to engage in risky behavior, as well as its associated genetic disposition. Unlike previous research on the topic that has relied on small non-representative samples, this project will use the largest collection of brain scans currently available, about 100,000 images. It will combine these images with genome-wide data and survey measures about risky behavior and analyze the data using advanced statistical techniques. This project will provide unique insights into the neuroanatomical and neurofunctional underpinnings of individual differences in risky behavior, and illuminate the causal relationships between genes, brain and behavior. As features of brain anatomy and function are sensitive to the influence of (early-) life environmental factors during sensitive developmental periods, the project can provide insight into how such factors influence the development of risky behavior during adulthood. All analyses will be based on pre-registered protocols and publicly available data and code, and as such will facilitate future research by generating reusable variables and analysis scripts. The educational plan includes the organization of workshops to facilitate a dialogue between geneticists, magnetic resonance imaging (MRI) researchers, and social scientists, as well as the development of teaching materials that introduce concepts in neuroscience and genetics to the next generation of scientists, business students, and the general public. This project integrates research, education and outreach programs aiming to break new grounds in the understanding of the neuroanatomical, neurofunctional and genetic underpinnings of individual differences in risky behavior. The proposed research includes high-quality T1, diffusion tensor imaging and resting-state functional MRI images. The research will combine this data with self-reported measures of risky behaviors, common single nucleotide polymorphisms (SNPs), results from large-scale genome-wide association studies (GWAS) of risky behaviors from independent samples, and demographic and environmental variables. The overall aims of this projects are to identify brain features that are robustly associated with the tendency to engage in risky behavior; annotate previously reported genetic associations of risky behavior using in-vivo brain images; employ statistical techniques to provide lower bounds of causal relationships between brain features and risky behavior; and to use machine-learning techniques for aggregating multimodal measurements across the brain to predict individual-level risky behavior. 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.