Strategy-dependent causal relationships between large-scale cortical activity and perceptual decisions

Animals can adopt different internally generated strategies to solve decision-making tasks, but whether cortical regions distinctly contribute to decisions under different strategies remains unknown. To address this problem, we analyzed three datasets comprising either cortical widefield imaging, or optogenetic inactivation of dozens of cortical locations in 54 mice, all performing the same sensory-evidence-accumulation task. Using Generalized Linear Model-Hidden Markov Models (GLM-HMMs), we found that the mice adopted one of three underlying strategies: an engaged, stimulus-driven state, and two disengaged states characterized by large side biases. The specific effects of inactivation of cortical regions depended on behavioral strategy: during engaged states, inactivation tended to increase side bias, while the opposite was true in biased states. For engaged states, these effects were most prominent when frontal regions were inactivated. Moreover, neural decoding analyses from cortex-wide activity revealed that frontal regions preferentially encode the animals' choices during engaged states relative to biased states. Our results suggest that distinct patterns of large-scale cortical dynamics underlie decisions under different task strategies and identify the frontal cortex as an important substrate of engaged-strategy control.