Hierarchical Deviant Processing in Auditory Cortex of Awake Mice.

Detecting patterns, and noticing unexpected pattern changes, in the environment is a vital aspect of sensory processing. Adaptation and prediction error responses are two components of neural processing related to these tasks, and previous studies in the auditory system in rodents show that these two components are partially dissociable in terms of the topography and latency of neural responses to sensory deviants. However, many previous studies have focused on repetitions of single stimuli, such as pure tones, which have limited ecological validity. In this study, we tested whether the auditory cortical activity shows adaptation to repetition of more complex sound patterns (bisyllabic pairs). Specifically, we compared neural responses to violations of sequences based on single stimulus probability only, against responses to more complex violations based on stimulus order. We employed an auditory oddball paradigm and monitored the auditory cortex (ACtx) activity of awake mice (N=8) using wide-field calcium imaging. We found that cortical responses were sensitive both to single stimulus probabilities and to more global stimulus patterns, as mismatch signals were elicited following both substitution deviants and transposition deviants. Notably, A2 area elicited larger mismatch signaling to those deviants than primary ACtx (A1), which suggests a hierarchical gradient of prediction error signaling in the auditory cortex. Such a hierarchical gradient was observed for late but not early peaks of calcium transients to deviants, suggesting that the late part of the deviant response may reflect prediction error signaling in response to more complex sensory pattern violations.