Dorsal prefrontal cortex drives perseverative behavior in mice

Perseveration – repeating one choice when others would generate larger rewards – is a common behavior, but neither its purpose nor neuronal mechanisms are understood. Here we demonstrate a neural correlate and causal role of dorsal prefrontal cortex, specifically anterior supplementary motor cortex (MOs) in perseveration in mice performing a dynamic reward learning task. An auditory go cue signaled mice to turn a wheel either left or right, with the reward probability of each action switching in blocks. Mice perseverated, gaining suboptimal reward, but were faster when making repeated choices. Neuropixels recordings found neurons whose activity correlated with perseveration and predicted rapid reaction times, almost exclusively in anterior MOs. Optogenetically inhibiting this region at choice time reduced perseveration and slowed reactions. In contrast, inactivating medial prefrontal cortex at choice time had no effect, but inactivating it after reward delivery impaired learning. In this task, therefore, anterior MOs reflects a perseverative decision variable, and is necessary for mediating the effect of this decision variable on choice and reaction time.