Predictive filtering of sensory response via orbitofrontal top-down input

Habituation is a crucial sensory filtering mechanism whose dysregulation can lead to a continuously intense world in disorders with sensory overload. While habituation is considered to require top-down predictive signaling to suppress irrelevant inputs, the exact brain loci storing the internal predictive model and the circuit mechanisms of sensory filtering remain unclear. We found that daily neural habituation in the primary auditory cortex (A1) was reversed by inactivation of the orbitofrontal cortex (OFC). Top-down projections from the ventrolateral OFC, but not other frontal areas, carried predictive signals that grew with daily sound experience and suppressed A1 via somatostatin-expressing inhibitory neurons. Thus, prediction signals from the OFC cancel out behaviorally irrelevant anticipated stimuli by generating their "negative images" in sensory cortices.