Inferring macroscopic intrinsic neural timescales using optimal control theory

Abstract

The temporal evolution of brain activity relies on complex interactions within and between brain regions that are mediated by neurobiology and connectivity. To understand these interactions, many large-scale efforts have measured structural connectivity, neural activity, gene expression, and cognition across multiple modalities and species. However, data-driven discovery of large-scale activity models remains difficult owing to the lack of flexible quantitative frameworks for estimating the interplay between brain structure and function while preserving biophysical realism. Here, we provide such a framework by integrating network control theory (NCT) with automatic differentiation to estimate model parameters with greater biophysical realism from data. Specifically, we estimate the structural form of regional self-inhibition--a quantity that is experimentally difficult to measure--from MRI data. Next, we demonstrate that the resulting model-based self-inhibition parameters correlate significantly with regions intrinsic neural timescales (INTs), neurobiological measures of gene expression and cell-type densities, as well as behavioral measures of cognition. We demonstrate consistent results across multiple datasets and species. Finally, we demonstrate that our self-inhibition parameters enable the efficient control of brain dynamics from fewer brain regions. Taken together, our results provide a simple and flexible quantitative framework that more accurately captures the interplay between brain structure, function, and dynamics with greater biophysical realism.