A microelectrode array-organoid interface for probing oscillatory behaviors and network-level functional characteristics in mini-brain models

The convergence of brain organoids and microelectrode arrays (MEAs) represents a transformative advancement in neuroscience, drug discovery, and the emerging field of organoid intelligence. However, the absence of refined analytical methods for extracting reliable and meaningful data continues to impede its full potential. By shifting from single-unit activity to local field potentials, we uncover the predominance of spatiotemporal slow oscillations, particularly within the delta range (<4 Hz), originating intrinsically from the organoids. Throughout development of the organoids, the intensity of oscillatory activity strongly correlates with neuronal maturity and cellular composition. Moreover, electrical or chemical stimulation can lead to rapid changes in oscillatory behavior. In ischemic stroke models, oxygen-glucose deprivation elicits changes in oscillatory patterns, accompanied by elevated delta-band coherence and increased global efficiency. Collectively, these findings demonstrate that the oscillatory activity is associated with network-level functional connectivity across developmental and physiological states, providing insights into neural development, disease modeling, and biocomputing.