Development of Optimal Sensory Feedback Strategies to Maximize Function After Tetraplegia

The overall goal of this study is to compare the sensations that are perceived from intracortical microstimulation (ICMS) to those perceived from peripheral nerve stimulation (PNS), and also to perceived sensations from a combination of ICMS and PNS. Preceding study Participants for this study will be individuals with a high-level spinal cord injury who are already enrolled in the "Reconnecting the Hand and Arm to the Brain (ReHAB)" clinical trial (ID# NCT03898804). The ReHAB clinical trial involves receiving tiny electrode arrays in the brain and small electrodes around some of the nerves in the arm. The goal of the ReHAB clinical trial is to restore arm and hand movement and sensation in individuals with paralysis from a spinal cord injury. Goals of this clinical trial The purpose of the proposed study is to investigate the perception and functional impact of sensory neurostimulation in participants with tetraplegia. Investigators will develop and implement novel paradigms of ICMS applied to primary somatosensory cortex (S1) and PNS applied to upper extremity nerves through chronically-implanted cuff electrodes. Investigators will also develop and assess hybrid neurostimulation paradigms involving paired application of ICMS and PNS. For each paradigm, investigators will quantify the perceived sensation with classic psychophysical methods. Investigators will also implement the approach into closed-loop tasks in virtual reality controlled through decoded cortical signals recorded from intracortical microelectrode arrays. Finally, investigators will assess the impact of each stimulation paradigm on residual sensory function. In Aim 1, investigators will develop a novel ICMS paradigm that attempts to reproduce both the temporal and spatial activation patterns that occur in S1 during normal touch. Investigators will compare this novel paradigm to other existing ICMS encoders. Investigators will assess the impact of each ICMS encoder on perceptual response, task performance in virtual reality (VR), and residual sensory function. In Aim 2, investigators will develop novel PNS paradigms and assess the efficacy of PNS for sensory feedback in people with tetraplegia for the first time. As in Aim 1, investigators will develop and compare several PNS encoders, including those that reproduce aspects of the peripheral response to normal touch and traditional linear encoders. We will assess the impact of each PNS encoder on perceptual response, task performance in VR, and residual sensory function. In Aim 3, we will develop hybrid neurostimulation paradigms that pair ICMS with PNS. We will assess the impact of stimulation encoder and stimulation amplitude on the perceived sensations generated by hybrid stimulation. We will then investigate the impact of PNS-ICMS timing delays within the hybrid neurostimulation paradigm on the perceptual response, functional impact, and impact on residual sensory function. All participants will participate in all aims and will receive all stimulation approaches and perform all tasks and measures. All participants will serve as their own control for the planned statistical analyses. The study will generate tens of thousands of perceptual response data points, hundreds of functional task data points, and hundreds of thousands of intracortical recordings (for exploratory analyses).