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.

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.

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.

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 arrays are used for recording neural signals at single-unit resolution and are promising tools for studying brain function and developing neuroprosthetics. Research is being done to increase the chronic performance and reliability of these probes, which tend to decrease or fail within several months of implantation. Although recording paradigms vary, studies focused on assessing the reliability and performance of these devices often perform recordings under anesthesia. However, anesthetics—such as isoflurane—are known to alter neural activity and electrophysiologic function. Therefore, we compared the neural recording performance under anesthesia (2% isoflurane) followed by awake conditions for probes implanted in the motor cortex of both male and female Sprague-Dawley rats. While the single-unit spike rate was significantly higher by almost 600% under awake compared to anesthetized conditions, we found no difference in the active electrode yield between the two conditions two weeks after surgery. Additionally, the signal-to-noise ratio was greater under anesthesia due to the noise levels being nearly 50% greater in awake recordings, even though there was a 14% increase in the peak-to-peak voltage of distinguished single units when awake. We observe that these findings are similar for chronic time points as well. Our observations indicate that either anesthetized or awake recordings are acceptable for studies assessing the chronic reliability and performance of intracortical microelectrode arrays.