Evaluating Electrode Charge Density in Chronic ICMS with Multi-Channel Microstimulation of Ultramicroelectrode Arrays

Introduction: Intracortical microstimulation (ICMS) offers a promising pathway to restore sensory functions for individuals with paralysis, primarily by targeting the primary somatosensory cortex (S1). However, the longevity and stability of ICMS are hindered by chronic foreign body responses that lead to device encapsulation by immune cells and decreased signal quality over time. To mitigate these effects, ultramicroelectrodes have been designed to improve biocompatibility and therefore improve long-term device performance. For stimulation applications, one of the challenges of smaller electrode-site areas is the increased current densities at the electrode which can damage the device or surrounding tissue. In this study, we evaluate the use of multiple electrode sites to deliver effective stimulation simultaneously while reducing the charge on each electrode site. The overarching goal of the work is to develop multichannel ultramicroelectrode arrays suitable for chronic neurostimulation.

Materials and

Methods: Ultramicroelectrode devices were custom designed with 26 electrodes of 5 µm and 10 µm diameters (19.63 µm^2 and 78.54 µm^2, respectively) as seen in Figure 1. To improve charge-storage capacity, electrodes were coated with a sputtered iridium oxide film (SIROF). The electrodes were implanted to a depth of 1700 µm in the somatosensory cortex. Stimuli were delivered to electrode sites at 320 Hz using 650 ms pulse trains with 0.2 ms phase duration and 0.04 ms interpulse intervals. The total charge injected per electrode site was limited to 0.8 nC/phase for 5 µm diameter sites and 2.4 nC/phase for 10 µm diameter sites. A modified conditioned avoidance behavioral paradigm [1] was used to determine detection thresholds in rats. Water-deprived rats were monitored for licking patterns, with safe trials (controls) and warning trials (ICMS stimulus). Detection thresholds were determined with an adaptive algorithm that decreased stimulus amplitude if the animal successfully detected the stimulus (“hit”) and increased if stimulus detection was unsuccessful (“miss”). The magnitude of the amplitude change decreased with each trial. This pattern was repeated until three reversals (hit followed by miss, or vice versa) was recorded at which point the detection threshold was calculated using the average of the stimulation amplitude for the last five trials.

Results, Conclusions, and Discussions: Chronic behavioral responses to neural stimulation were observed, with consistent thresholds achieved by stimulating multiple channels simultaneously. To test different combinations, all animals started with stimulation of 6 of the 10 µm diameter sites and after exhibiting threshold, were then tested sequentially by systematically lowering the total surface area (i.e., dropping stimulation sites). As seen in Figure 2, stimulation has been effective down to a combined surface area of 78.54 µm^2 (four of the 5 µm diameter sites or equivalently one of the 10 µm diameter sites). As seen in previous research [2], the charge per electrode increased as the number of stimulated electrodes decreased while conversely the total charge per threshold decreased. In one subject, for thresholds obtained using 6 of the 10 µm diameter sites (i.e. the largest surface area stimulated, 471.24 µm^2) the average charge per phase per electrode was 1.23 nC/phase, while the average total charge applied for the same electrode configuration was 7.38 nC/phase. For thresholds with 4 of the 5 µm diameter sites (i.e. the smallest surface area stimulated thus far, 78.54 µm^2) the average charge per phase per electrode was 0.63 nC/phase, while the average total charge applied for the same electrode configuration was 2.51 nC/phase. These insights highlight the feasibility of multi-channel intracortical microstimulation and pave the way for further innovations in brain-machine interface technology to restoring sensory functions for individuals with paralysis The ability to achieve reliable and chronic ICMS using multichannel ultramicroelectrode arrays opens new avenues for enhancing sensory feedback and improving the quality of life for persons with paralysis.

References:
[1] J. B. Kelly et al., “Behavioral limits of auditory temporal resolution in the rat: Amplitude modulation and duration discrimination,” J. Comp. Psychol., vol. 120, pp. 98–105, May 2006.
[2] Kunigk, N. G., et al (2022). Reducing behavioral detection thresholds per electrode via synchronous, spatially-dependent intracortical microstimulation. Frontiers in Neuroscience. 16:876142. doi: 10.3389/fnins.2022.876142

Acknowledgements (Optional): This material is based upon work supported by the National Institutes of Health under Grant NIH 1U01NS126052-01 “Engineering the neuronal response to electrical microstimulation.” (PIs, Kevin J. Otto and Mark E. Orazem)