Vatsyayan, R.; Khoury, F.; Porter, T. S.; Sinopoulou, E.; Day, H.; Russman, S.; Montgomery-Walsh, R.; Shukla, K.; Saad, H.; Bourhis, A. M.; Lee, J.; Tonsfeldt, K. J.; Nagamori, A.; Sang U, H.; Roth, D. M.; Hall, D.; Ben-Haim, S.; Azim, E.; Yaksh, T. L.; Khalessi, A.; Tuszynski, M.; Dayeh, S. A.

Clinical neuromodulation primarily employs near-field low frequency electrical stimulation to activate neurons in the immediate vicinity of the electrode. We introduce Adaptive Charge Modulation (ACM), a spatiotemporal, charge-balanced stimulation strategy that focuses activation at deep tissue sites distant from the stimulating contacts. We apply ACM to stimulate deep regions of the spinal cord, distant from dorsal root entry zones which are preferentially activated during low frequency stimulation (LFS). ACM applies multipolar, biphasic rectangular pulses to exceed activation thresholds in deeper neuronal populations, with reduced surface activation, potentially due to high-frequency suppression of neural activity. In epidural spinal cord stimulation in rats, ACM achieved single-muscle selectivity among fourteen monitored muscles with minimal co-activation of other muscles. Using simultaneous, high spatiotemporal resolution, 2,112-channel brain-spine recordings, we characterized the response latencies and pathways consistent with focal recruitment at depth. We observed chronic stability of the electrode and ACM in freely behaving animals over 68 days post-implantation. By enabling focal activation with epidural surface electrodes, ACM may expand the reach and precision of neuromodulation and neural interfaces.