Configuring intracortical microelectrode arrays and stimulus parameters to minimize neuron loss during prolonged intracortical electrical stimulation

BACKGROUND: Previous studies have shown that neurons of the cerebral cortex can be injured by implantation of, and stimulation with, implanted microelectrodes. OBJECTIVES: Objective 1 was to determine parameters of microstimulation delivered through multisite intracortical microelectrode arrays that will activate neurons of the feline cerebral cortex without causing loss of neurons. OBJECTIVE: 2 was to determine if the stimulus parameters that induced loss of cortical neurons differed for all cortical neurons vs. the subset of inhibitory neurons expressing parvalbumin. METHODS: The intracortical microstimulation was applied for 7 h/day for 20 days (140 h). Microelectrode site areas were 2000 and 4000 μm(2), Q was 2–8 nanocoulombs (nC) at 50 Hz, and QD was 50–400 μcoulombs/cm(2). RESULTS: Neuron loss due to stimulation was minimal at Q = 2 Ncp, but at 8 Ncp, 20%–50% of neurons within 250 μm of the stimulated microelectrodes were lost, compared to unstimulated microelectrodes. Loss was greatest in tissue facing electrode sites. Stimulation-induced loss was similar for neurons labeled for NeuN and for inhibitory neurons expressing parvalbumin. Correlation between neuron loss and QD was not significant. Electrodes in the medullary pyramidal tract recorded neuronal activity evoked by stimulation in the cerebral cortex. The pyramidal neurons were activated by intracortical stimulation of 2 nC/phase. 140 h of microstimulation at 2 nC/phase and 50 Hz induced minimal neuron loss.