Planar amorphous silicon carbide microelectrode arrays for chronic recording in rat motor cortex.

Chronic implantation of intracortical microelectrode arrays (MEAs) capable of recording from individual neurons can be used for the development of brain-machine interfaces. However, these devices show reduced recording capabilities under chronic conditions due, at least in part, to the brain's foreign body response (FBR). This creates a need for MEAs that can minimize the FBR to possibly enable long-term recording. A potential approach to reduce the FBR is the use of MEAs with reduced cross-sectional geometries. Here, we fabricated 4-shank amorphous silicon carbide (a-SiC) MEAs and implanted them into the motor cortex of seven female Sprague-Dawley rats. Each a-SiC MEA shank was 8 µm thick by 20 µm wide and had sixteen sputtered iridium oxide film (SIROF) electrodes (4 per shank). A-SiC was chosen as the fabrication base for its high chemical stability, good electrical insulation properties, and amenability to thin film fabrication. Electrochemical analysis and neural recordings were performed weekly for 4 months. MEAs were characterized pre-implantation in buffered saline and in vivo using electrochemical impedance spectroscopy and cyclic voltammetry at 50 mV/s and 50,000 mV/s. Neural recordings were analyzed for single unit activity. At the end of the study, animals were sacrificed for immunohistochemical analysis. We observed statistically significant, but small, increases in 1 and 30 kHz impedance values and 50,000 mV/s charge storage capacity over the 16-week implantation period. Slow sweep 50 mV/s CV and 1 Hz impedance did not significantly change over time. Impedance values increased from 11.6 MΩ to 13.5 MΩ at 1 Hz, 1.2 MΩ-2.9 MΩ at 1 kHz, and 0.11 MΩ-0.13 MΩ at 30 kHz over 16 weeks. The median charge storage capacity of the implanted electrodes at 50 mV/s was 58.1 mC/cm2 on week 1 and 55.9 mC/cm2 on week 16, and at 50,000 mV/s, 4.27 mC/cm2 on week 1 and 5.93 mC/cm2 on week 16. Devices were able to record neural activity from 92% of all active channels at the beginning of the study, At the study endpoint, a-SiC devices were still recording single-unit activity on 51% of electrochemically active electrode channels. In addition, we observed that the signal-to-noise ratio experienced a small decline of -0.19 per week. We also classified observed units as fast and slow repolarizing based on the trough-to-peak time. Although the overall presence of single units declined, fast and slow repolarizing units declined at a similar rate. At recording electrode depth, immunohistochemistry showed minimal tissue response to the a-SiC devices, as indicated by statistically insignificant differences in activated glial cell response between implanted brains slices and contralateral sham slices at 150 µm away from the implant location, as evidenced by GFAP staining. NeuN staining revealed the presence of neuronal cell bodies close to the implantation site, again statistically not different from a contralateral sham slice. These results warrant further investigation of a-SiC MEAs for future long-term implantation neural recording studies.

Reactive Amine Functionalized Microelectrode Arrays Provide Short-Term Benefit but Long-Term Detriment to In Vivo Recording Performance.

Intracortical microelectrode arrays (MEAs) are used for recording neural signals. However, indwelling devices result in chronic neuroinflammation, which leads to decreased recording performance through degradation of the device and surrounding tissue. Coating the MEAs with bioactive molecules is being explored to mitigate neuroinflammation. Such approaches often require an intermediate functionalization step such as (3-aminopropyl)triethoxysilane (APTES), which serves as a linker. However, the standalone effect of this intermediate step has not been previously characterized. Here, we investigated the effect of coating MEAs with APTES by comparing APTES-coated to uncoated controls in vivo and ex vivo. First, we measured water contact angles between silicon uncoated and APTES-coated substrates to verify the hydrophilic characteristics of the APTES coating. Next, we implanted MEAs in the motor cortex (M1) of Sprague-Dawley rats with uncoated or APTES-coated devices. We assessed changes in the electrochemical impedance and neural recording performance over a chronic implantation period of 16 weeks. Additionally, histology and bulk gene expression were analyzed to understand further the reactive tissue changes arising from the coating. Results showed that APTES increased the hydrophilicity of the devices and decreased electrochemical impedance at 1 kHz. APTES coatings proved detrimental to the recording performance, as shown by a constant decay up to 16 weeks postimplantation. Bulk gene analysis showed differential changes in gene expression between groups that were inconclusive with regard to the long-term effect on neuronal tissue. Together, these results suggest that APTES coatings are ultimately detrimental to chronic neural recordings. Furthermore, interpretations of studies using APTES as a functionalization step should consider the potential consequences if the final functionalization step is incomplete.

The effect of a Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP) coating on the chronic recording performance of planar silicon intracortical microelectrode arrays.

Intracortical microelectrode arrays (MEAs) are used to record neural activity. However, their implantation initiates a neuroinflammatory cascade, involving the accumulation of reactive oxygen species, leading to interface failure. Here, we coated commercially-available MEAs with Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP), to mitigate oxidative stress. First, we assessed the in vitro cytotoxicity of modified sample substrates. Then, we implanted 36 rats with uncoated, MnTBAP-coated ("Coated"), or (3-Aminopropyl)triethoxysilane (APTES)-coated devices - an intermediate step in the coating process. We assessed electrode performance during the acute (1-5 weeks), sub-chronic (6-11 weeks), and chronic (12-16 weeks) phases after implantation. Three subsets of animals were euthanized at different time points to assess the acute, sub-chronic and chronic immunohistological responses. Results showed that MnTBAP coatings were not cytotoxic in vitro, and their implantation in vivo improved the proportion of electrodes during the sub-chronic and chronic phases; APTES coatings resulted in failure of the neural interface during the chronic phase. In addition, MnTBAP coatings improved the quality of the signal throughout the study and reduced the neuroinflammatory response around the implant as early as two weeks, an effect that remained consistent for months post-implantation. Together, these results suggest that MnTBAP coatings are a potentially useful modification to improve MEA reliability.

Antioxidant Dimethyl Fumarate Temporarily but Not Chronically Improves Intracortical Microelectrode Performance.

Intracortical microelectrode arrays (MEAs) can be used in a range of applications, from basic neuroscience research to providing an intimate interface with the brain as part of a brain-computer interface (BCI) system aimed at restoring function for people living with neurological disorders or injuries. Unfortunately, MEAs tend to fail prematurely, leading to a loss in functionality for many applications. An important contributing factor in MEA failure is oxidative stress resulting from chronically inflammatory-activated microglia and macrophages releasing reactive oxygen species (ROS) around the implant site. Antioxidants offer a means for mitigating oxidative stress and improving tissue health and MEA performance. Here, we investigate using the clinically available antioxidant dimethyl fumarate (DMF) to reduce the neuroinflammatory response and improve MEA performance in a rat MEA model. Daily treatment of DMF for 16 weeks resulted in a significant improvement in the recording capabilities of MEA devices during the sub-chronic (Weeks 5-11) phase (42% active electrode yield vs. 35% for control). However, these sub-chronic improvements were lost in the chronic implantation phase, as a more exacerbated neuroinflammatory response occurs in DMF-treated animals by 16 weeks post-implantation. Yet, neuroinflammation was indiscriminate between treatment and control groups during the sub-chronic phase. Although worse for chronic use, a temporary improvement (<12 weeks) in MEA performance is meaningful. Providing short-term improvement to MEA devices using DMF can allow for improved use for limited-duration studies. Further efforts should be taken to explore the mechanism behind a worsened neuroinflammatory response at the 16-week time point for DMF-treated animals and assess its usefulness for specific applications.

Chronic Stability of Local Field Potentials Using Amorphous Silicon Carbide Microelectrode Arrays Implanted in the Rat Motor Cortex.

Implantable microelectrode arrays (MEAs) enable the recording of electrical activity of cortical neurons, allowing the development of brain-machine interfaces. However, MEAs show reduced recording capabilities under chronic conditions, prompting the development of novel MEAs that can improve long-term performance. Conventional planar, silicon-based devices and ultra-thin amorphous silicon carbide (a-SiC) MEAs were implanted in the motor cortex of female Sprague-Dawley rats, and weekly anesthetized recordings were made for 16 weeks after implantation. The spectral density and bandpower between 1 and 500 Hz of recordings were compared over the implantation period for both device types. Initially, the bandpower of the a-SiC devices and standard MEAs was comparable. However, the standard MEAs showed a consistent decline in both bandpower and power spectral density throughout the 16 weeks post-implantation, whereas the a-SiC MEAs showed substantially more stable performance. These differences in bandpower and spectral density between standard and a-SiC MEAs were statistically significant from week 6 post-implantation until the end of the study at 16 weeks. These results support the use of ultra-thin a-SiC MEAs to develop chronic, reliable brain-machine interfaces.

Intracortical Microelectrode Array Unit Yield under Chronic Conditions: A Comparative Evaluation.

While microelectrode arrays (MEAs) offer the promise of elucidating functional neural circuitry and serve as the basis for a cortical neuroprosthesis, the challenge of designing and demonstrating chronically reliable technology remains. Numerous studies report "chronic" data but the actual time spans and performance measures corresponding to the experimental work vary. In this study, we reviewed the experimental durations that constitute chronic studies across a range of MEA types and animal species to gain an understanding of the widespread variability in reported study duration. For rodents, which are the most commonly used animal model in chronic studies, we examined active electrode yield (AEY) for different array types as a means to contextualize the study duration variance, as well as investigate and interpret the performance of custom devices in comparison to conventional MEAs. We observed wide-spread variance within species for the chronic implantation period and an AEY that decayed linearly in rodent models that implanted commercially-available devices. These observations provide a benchmark for comparing the performance of new technologies and highlight the need for consistency in chronic MEA studies. Additionally, to fully derive performance under chronic conditions, the duration of abiotic failure modes, biological processes induced by indwelling probes, and intended application of the device are key determinants.