Intracortical microstimulation can be successfully used to manipulate neuronal activity and connectivity, thus representing a potentially powerful tool to steer neuroplasticity occurring after brain injury. Activity-dependent stimulation (ADS), in which the spikes recorded from a single neuron are used to trigger stimulation at another cortical location, is able to potentiate cortical connections between distant brain areas. Here, we developed an experimental procedure and a computational pipeline aimed at investigating the ability of ADS to induce changes in intra-cortical activity of healthy anesthetized rats.