Spike-based analysis of brain injured anesthetized animals undergoing closed-loop intracortical stimulation

Acquired brain injuries, such as stroke, are a major cause of long-term disability worldwide. When an injury occurs within primary motor cortex (M1) there is both a loss of descending information to the spinal cord and a disruption in the communication within and between spared regions, which can lead to hemiparesis and other motor dysfunction. Recently, activity-dependent stimulation (ADS), a closed loop intracortical neurostimulation technique, was shown to significantly improve behavioral recovery in rodent models following a unilateral traumatic brain injury in the primary motor cortex. While behavioral benefits have been described, the neurophysiological changes in spared areas in response to this type of stimulation have not been fully characterized. In this study, we investigated how neuronal activity is modified 1) following an injury to primary motor cortex and 2) in response to an ADS protocol. Intracortical microelectrode array were inserted in the ipsilesional rostral forelimb area (RFA) to record spike activity and to trigger intracortical microstimulation in the somatosensory cortex (S1). Following a rodent (Long Evans) model of ischemic injury using endothelin-1, a potent vasoconstrictor, was injected unilaterally through the extent of the forelimb area of primary motor cortex. We found that an ischemic injury in M1 led to an overall increase in spike activity within RFA and S1. Subsequent treatment with ADS promoted the generation of synchronized patterns in both RFA and S1.