📝 SummarXiv

Abstract

Mismatch negativity (MMN) in humans reflects deviance detection (DD), a core neural mechanism of predictive processing. However, the fundamental principles by which DD emerges and matures during early cortical development-potentially providing a neuronal scaffold for MMN-remain unclear. Here, we tracked the development of DD in dissociated cortical cultures grown on high-density CMOS microelectrode arrays from 10 to 35 days in vitro (DIV). Cultures were stimulated with oddball and many-standards control paradigms while spontaneous and evoked activity were recorded longitudinally. At early stages, stimulus-evoked responses were confined to fast components reflecting direct activation. From DIV15-20 onward, robust late responses appeared, and deviant stimuli progressively evoked stronger responses than frequent and control stimuli, marking the onset of DD. By DIV30, responses became stronger, faster, and more temporally precise. Neuronal avalanche analysis revealed a gradual transition from subcritical to near-critical dynamics, with cultures exhibiting power-law statistics showing the strongest deviant responses. Nonetheless, DD was also present in non-critical networks, indicating that criticality is not required for its emergence but instead stabilizes and amplifies predictive processing as networks mature. Early oddball experience reinforces the deviant pathway, resulting in faster conduction along those circuits. However, as frequent and deviant pathways become less distinct, the deviance detection index is reduced. Together, these findings demonstrate that DD arises intrinsically through local circuit maturation, while self-organization toward criticality and early experience further refine its strength and timing, providing mechanistic insight into predictive coding in simplified cortical networks and informing the design of adaptive, prediction-sensitive artificial systems.