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

Abstract

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 mm 2 , Q was 2e8 nanocoulombs (nC) at 50 Hz, and QD was 50 e400 mcoulombs/cm 2 .Results: Neuron loss due to stimulation was minimal at Q ¼ 2 Ncp, but at 8 Ncp, 20%e50% of neurons within 250 mm 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.

Stimulation-Evoked Effective Connectivity (SEEC): An in-vivo approach for defining mesoscale corticocortical connectivity

“…Furthermore, similar to our findings, ICMS-evoked neural activity measured with intrinsic optical imaging corresponds with both anatomical connectivity and resting-state functional connectivity (45). However, the stimulation amplitudes in these studies were several times higher than the amplitudes used here, increasing the volume of direct activation, and potentially the risk of cortical damage with repeated stimulation (46). Additionally, while an area of cortex can be imaged repeatably, fMRI in animal models requires the use of anesthesia for scanning and it is technically challenging to maintain the visual field necessary for repeated optical imaging.…”

“…In particular, ICMS has also been used in conjunction with fMRI or intrinsic optical imaging to measure intra-and interregional connectivity (22)(23)(24)(25)(26)43). However, the stimulation amplitudes in these studies were several times higher than the amplitudes used here, increasing the risk of cortical damage with repeated stimulation (44). Additionally, while an area of cortex can be repeatably imaged, fMRI in animal models requires the use of anesthesia for scanning and it is technically challenging to maintain the visual field necessary for repeated optical imaging .…”

A portable neurostimulator circuit with anodic bias enhances stimulation injection capacity

“…Therefore, figure 4(B) ) illustrates that applying a 600 mV anodic bias enhanced charge injection greatly, even leaving additional capability to inject more currents. Our stimulator’s maximum current output of 160 μ A is likely enough for most in vivo microstimulation applications in terms of activating neural tissues [ 7 , 23 , 31 ].…”

“…We can currently use the electronics in benchtop or intraoperative settings, but a longer-term purpose of implementing the Bluetooth interface would be for use in freely-behaving small animals (although this utility is not a main focus of this report). The current physical dimension may be small and light enough for the rats as a backpack-worn stimulator as similarly done in a recent long-term stimulation safety study in the cats [ 23 ]. There are several benefits of our wireless system, including: (a) stimulation parameterization and data transfer without restricting animal mobility extracorporeally and risking connector failure after repeated mating, (b) reduced tethering of animal’s body to the instrument which may introduce less stress during long-term stimulation experiments and, thus, enhance signal fidelity and reproducibility, and (c) improved scalability of stimulation channels without adding bulkiness to the cables and connectors.…”

“…This ensures that the system avoids injecting extra net charge into the electrolyte or tissues, potentially resulting in tissue damage in vivo . Our recent work involving a 400 mV-anodic bias in a long-term in vivo study reported that intracortical stimulation of feline pyramidal neurons for 20 d resulted in minimal damage compared to control tissue [ 23 ].…”