Cortical processing of flexible and context-dependent sensorimotor sequences.

The brain generates complex sequences of movements that can be flexibly configured based on behavioural context or real-time sensory feedback 1 , but how this occurs is not fully understood. Here we developed a 'sequence licking' task in which mice directed their tongue to a target that moved through a series of locations. Mice could rapidly branch the sequence online based on tactile feedback. Closed-loop optogenetics and electrophysiology revealed that the tongue and jaw regions of the primary somatosensory (S1TJ) and motor (M1TJ) cortices 2 encoded and controlled tongue kinematics at the level of individual licks. By contrast, the tongue 'premotor' (anterolateral motor) cortex 3-10 encoded latent variables including intended lick angle, sequence identity and progress towards the reward that marked successful sequence execution. Movement-nonspecific sequence branching signals occurred in the anterolateral motor cortex and M1TJ. Our results reveal a set of key cortical areas for flexible and context-informed sequence generation.