Abstract: The disclosure provides a biological brain-computer interface comprising genetically modified cells engrafted onto an adult mammal (e.g., mouse) above cortical layer 1, forming an artificial cortical layer termed layer zero (L0). Following engraftment, L0 goes through a developmental process characterized by synchronous waves of activity that gradually recede to resemble spontaneous cortical activity. Axons and dendrites from L0 nondestructively infiltrated the host cortex and formed synaptic connections necessary for bidirectional communication with the brain.