The ability to flexibly switch our response to external stimuli according to contextual information is critical for successful interactions with a complex world. Context-dependent computations have been described across many domains, yet the neural mechanisms of how inputs to a brain region interact with its local dynamics, to produce context-dependent computation, remain poorly understood. We developed a novel pulse-based behavioral task to study context-dependent selection and accumulation of evidence for decision-making, which permitted an in-depth examination of the mathematics underlying the networks that implement this computation. We demonstrate that, under assumptions supported by both monkey and rat data, the space of possible network mechanisms is spanned by the combination of three different components, each with specific behavioral and anatomical implications. We further show that existing electrophysiological and modeling data are compatible with the full variety of possible combinations of these components, suggesting that different individuals could use different component combinations. To study variations across subjects, we developed a rat task requiring context-dependent evidence accumulation, and trained many subjects on it. Consistent with theoretical predictions, neural and behavioral analysis revealed substantial heterogeneity across rats, despite uniformly good task performance. The theory further predicts a specific link between behavioral and neural signatures, which was robustly supported in the data. Our results provide a new experimentally-supported theoretical framework to analyze biological and artificial systems performing flexible decision-making tasks, open the door to cellular-resolution studies of individual variability in higher cognition, and provide insights into neural mechanisms of context-dependent computation more generally.
Carlos Brody is professor of neuroscience and molecular biology at Princeton University and a Howard Hughes Medical Institute Investigator. He completed his Ph.D. in 1997 in computation and neural systems with John Hopfield at the California Institute of Technology. Starting in 2001, he led a computational neuroscience group as an assistant professor at Cold Spring Harbor Laboratory. Inspired by the efforts that Zachary Mainen and Anthony Zador’s experimental groups at Cold Spring Harbor Laboratory were making in developing highly controlled behaviors for rats, Brody added experimental approaches to his research portfolio. His focus is on novel quantitative behaviors that allow exploring high-level cognitive questions using powerful emerging tools for studying neural mechanisms in rats. Brody’s group now uses rats to investigate the neural bases of decision-making, working memory and executive control using a combination of high-throughput semiautomated behavior as well as computational, electrophysiological, pharmacological and optogenetic methods. Brody moved to Princeton University in 2006 and has been a Howard Hughes Medical Institute Investigator since 2008.
Current Project: Population Analysis of Cognitive Variables