Emergence of Deviance Detection in Cortical Cultures Through Maturation, Criticality, and Early Experience

Mismatch negativity (MMN) in humans is widely interpreted as reflecting deviance detection (DD) within predictive processing frameworks. However, the developmental processes by which DD emerges and matures during early cortical development remain incompletely understood. Here, we longitudinally tracked the development of DD in dissociated cortical cultures grown on high‐density CMOS microelectrode arrays from Day In Vitro (DIV) 10 to DIV30 (Study 1) and compared cultures with and without early structured stimulation at DIV31–35 (Study 2). Cultures were stimulated with oddball and many‐standards control paradigms while spontaneous and evoked activity were recorded. In Study 1, stimulus‐evoked responses at early stages were largely confined to fast components corresponding to direct stimulation effects. From DIV15 onward, robust late responses emerged, and deviant stimuli evoked stronger responses than frequent and control stimuli, marking the emergence of DD as defined in this study. By DIV30, responses became stronger, faster, and more temporally precise. Neuronal avalanche analysis revealed a transition from subcritical to near‐critical dynamics across development. Cultures exhibiting power‐law–like statistics showed larger DD indices, although DD was also observed in non‐critical networks. These findings indicate that critical dynamics are not required for DD, but critical‐like states are associated with more robust and differentiated DD responses as networks mature. In Study 2, both groups shifted toward power‐law–like avalanche distributions, with no significant difference in their developmental trajectories. At DIV31–35, stimulated cultures had earlier peak responses and lower DD indices than controls, but these group differences were not significant. Together, these findings indicate that dissociated cortical cultures can exhibit DD under simplified in vitro conditions and that its developmental trajectory is associated with network maturation and self‐organization toward critical‐like dynamics.