AUTHOR=Kunigk Nicolas G. , Urdaneta Morgan E. , Malone Ian G. , Delgado Francisco , Otto Kevin J. TITLE=Reducing Behavioral Detection Thresholds per Electrode via Synchronous, Spatially-Dependent Intracortical Microstimulation JOURNAL=Frontiers in Neuroscience VOLUME=Volume 16 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.876142 DOI=10.3389/fnins.2022.876142 ISSN=1662-453X ABSTRACT=Intracortical microstimulation (ICMS) has shown promise in restoring quality of life to patients suffering from paralysis, specifically when used in the primary somatosensory cortex (S1). However, these benefits can be hampered by long-term degradation of electrode performance due to the brain’s foreign body response. Advances in microfabrication techniques have allowed for the development of neuroprostheses with subcellular electrodes, which are characterized by greater versatility and a less detrimental immune response during chronic use. These probes are hypothesized to enable more selective, higher-resolution stimulation of cortical tissue with long-term implants. However, microstimulation using physiologically relevant charges with these smaller-scale devices can damage electrode sites and reduce the efficacy of the overall device. Studies have shown promise in bypassing this limitation by spreading the stimulation charge between multiple channels in an implanted electrode array, but to our knowledge the usefulness of this strategy in laminar arrays with electrode sites spanning each layer of the cortex remains unexplored. To investigate the efficacy of simultaneous multi-channel ICMS in electrode arrays with stimulation sites spanning cortical depth, we implanted laminar electrode arrays in the primary somatosensory cortex of rats trained in a behavioral avoidance paradigm. By measuring detection thresholds, we were able to quantify improvements in ICMS performance using a simultaneous multi-channel stimulation paradigm. The charge required per site to elicit detection thresholds was halved when stimulating from two adjacent electrode sites. This reduction in threshold charge was increased by stimulating with more than two channels and decreased with greater distance between stimulating channels. Our findings suggest that these improvements are based on the synchronicity and polarity of each stimulus, and that the per-site charge reductions are seen regardless of the cortical depth of each utilized channel. These results have implications for the feasibility of stimulation regimes in future advanced neuroprosthetic devices.