Neural interface instructs layer 4-appropriate circuit reconstruction with engrafted human brain organoids and improves visually guided behavior

Repairing precise neural microcircuitry after cortical injury remains a pivotal challenge. Human brain organoids (hBOs) are a promising cell source, but disorganized integration limits their therapeutic potential. Here, we demonstrated that targeted neuromodulation, steered by endogenous narrowband gamma (NBG) rhythms, instructed structural and functional integration of hBO grafts in the injured adult mouse visual cortex. Using a neural interface system, we promoted general graft-host coupling and then delivered NBG-rhythmic stimulation to specific functional clusters. This strategy guided the emergence of layer 4-appropriate molecular and functional properties in grafts, enabled bidirectional connectivity with the host visual circuit, and supported the development of advanced visual processing, including direction selectivity in hBO neurons. Electrophysiologically, graft spiking phase locked to host NBG oscillations. Behaviorally, host visual acuity and contrast sensitivity were significantly restored. Our work established a framework for circuit-level repair, highlighting a synergistic strategy that moves beyond cell replacement to direct the assembly of neural grafts.