Reducing Behavioral Detection Thresholds per Electrode via Synchronous, Spatially-Dependent Intracortical Microstimulation

Abstract

Intracortical microstimulation (ICMS) has shown promise in restoring quality of life to patients suffering from paralysis, specifically when used in the primary somatosensory cortex (S1). However, these benefits can be hampered by long-term degradation of electrode performance due to the brain’s foreign body response. Advances in microfabrication techniques have allowed for the development of neuroprostheses with subcellular electrodes, which are characterized by greater versatility and a less detrimental immune response during chronic use. These probes are hypothesized to enable more selective, higher-resolution stimulation of cortical tissue with long-term implants. However, microstimulation using physiologically relevant charges with these smaller-scale devices can damage electrode sites and reduce the efficacy of the overall device. Studies have shown promise in bypassing this limitation by spreading the stimulation charge between multiple channels in an implanted electrode array, but to our knowledge the usefulness of this strategy in laminar arrays with electrode sites spanning each layer of the cortex remains unexplored. To investigate the efficacy of simultaneous multi-channel ICMS in electrode arrays with stimulation sites spanning cortical depth, we implanted laminar electrode arrays in the primary somatosensory cortex of rats trained in a behavioral avoidance paradigm. By measuring detection thresholds, we were able to quantify improvements in ICMS performance using a simultaneous multi-channel stimulation paradigm. The charge required per site to elicit detection thresholds was halved when stimulating from two adjacent electrode sites, although the overall charge used by the implant was increased. This reduction in threshold charge was more pronounced when stimulating with more than two channels and lessened with greater distance between stimulating channels. Our findings suggest that these improvements are based on the synchronicity and polarity of each stimulus, leading us to conclude that these improvements in stimulation efficiency per electrode are due to charge summation as opposed to a summation of neural responses to stimulation. Additionally, the per-site charge reductions are seen regardless of the cortical depth of each utilized channel. This evocation of physiological detection thresholds with lower stimulation currents per electrode site has implications for the feasibility of stimulation regimes in future advanced neuroprosthetic devices, which could benefit from reducing the charge output per site.

Layer-dependent stability of intracortical recordings and neuronal cell loss

“…A potential limitation of our results is that all of the electrodes in our study were subject to intracortical microstimulation (ICMS) experiments ( Urdaneta et al, 2019 ; Kunigk et al, 2022 ; Urdaneta et al, 2022 ); it is unclear how this ICMS may have affected recording performance. Despite the lack of unstimulated electrodes as a control group, all microstimulation charges were distributed across all channels.…”

Amplitude- and frequency-dependent activation of layer II/III neurons by intracortical microstimulation

“…It was noted that the sensation features, e.g., sensory perception intensity, spatial discrimination, etc., can be finely tuned by adjusting the stimulation parameters. 4 , 5 , 7 , 8 , 9 , 10 , 11 , 12 However, different results were observed: some studies showed a linear positive relationship between stimulation amplitude and magnitude of sensation up to the tested maximal stimulation intensity (16 nC per phase [ph]), 4 , 5 whereas others demonstrated a plateau effect above 12 nC/ph. 4 Schmidt et al.…”

Cortical layering disrupts multi-electrode current steering

“…Although the distribution of neural activation from stimulation is not well understood, it is often assumed that artificial electrical stimulation evokes neural activity spherically from the point of stimulation which lead to the theory of current steering [44][45][46][47]. However, we have shown that the influences of stimulation are different when electrodes are positioned perpendicular to the cortical layers compared to parallel.…”

“…Multilayer dual-electrode stimulation for prosthetics would cause the entire column to activate which could make the propagation of the artificial stimulation through the visual hierarchy more likely as more feedforward circuits become active. It has been previously shown that the perelectrode detection thresholds with dual-electrode stimulation decrease regardless of the stimulation layer in rat somatosensory cortex [47]. Given the lack of change in the neural activity curves and peak locations of our dual-electrode data in comparison to the single-electrode data, less charge can be input at two single electrodes while achieving the same level of neural activity in the column.…”