The Effect of an Antioxidant Coatings on the Recording Performance of Planar Silicon Intracortical Microelectrode Arrays

Introduction:: Intracortical Microelectrode Arrays (MEAs) can record neural activity from the brain and are used to develop brain-machine interfaces and to advance understanding of brain circuitry. However, implantation of these devices initiates a neuroinflammatory cascade, potentially resulting in reactive oxygen species that accumulate around the implant site, resulting in neuronal dysfunction. This process may contribute, at least in part, to the failure at the interface because the ability of MEAs to record is related to the proximity of viable neurons around the implant. Our group has developed an antioxidant coating based on the immobilization of mimetic for superoxide dismutase – a protective enzyme that degrades harmful superoxide anions into less reactive elements – for application to MEA substrates. Here, the goal was to investigate the effect of these coatings on the MEA recording performance in-vivo.


Materials and Methods:: Animal procedures were approved by the University of Texas at Dallas IACUC. Male Sprague Dawley rats were implanted with coated or uncoated (control) MEAs targeting the primary motor cortex (M1) of the brain. Neurophysiological data were recorded weekly for 10 minutes under anesthesia at a sampling rate of 40 kHz for 16 weeks after implantation and then filtered between 300-3000 Hz. Individual spike waveforms were extracted using a -4σ threshold and units were sorted using K-means clustering. Signal quality was assessed by quantifying the noise levels, the single unit voltage peak-to-peak, and the signal-to-noise levels. Analysis of data was done in bin durations corresponding to the progression of the neuroinflammation process. The acute period was defined as 1 to 5 weeks post-implantation; sub-chronic as 6 to 11 weeks; and chronic as 12-16 weeks. The active electrode yield was then calculated as the proportion of total electrode sites that captured at least one single unit for at least 50% of recordings sessions during each neuroinflammation phase. A two-proportion z-test was used to calculate statistical differences between groups with p< 0.05 considered as significant. For all other parameters, a Kruskal-Wallis test was performed for non-parametric multiple comparisons with correction by controlling for the False Discovery Rate using the Benjamini, Krieger and Yekutieli method.

Results, Conclusions, and Discussions:: Coated and uncoated MEAs showed similar proportion of active electrodes upon implantation and during the acute phase of neuroinflammation (coated: 58.3% and uncoated: 65.0%; p = 0.87). The proportion of active electrodes rapidly declined for the uncoated controls during the sub-chronic and chronic phases (sub-chronic: 42.2%, p = 0.0001 vs. acute; chronic: 50.0%, p = 0.008 vs. acute), while the coated MEAs remained mostly stable (sub-chronic: 62.5%, p = 0.77 vs. acute; chronic: 54.2%, p = 0.24 vs. acute). The difference between coated and uncoated MEAs was significant for the sub-chronic phase (p = 0.0004) but not for the chronic phase (p = 0.24). Noise levels were lower for coated MEAs compared to the uncoated controls during all phases of inflammation (p < 0.05) while the voltage peak-to-peak was comparable between groups. This resulted in a higher signal-to-noise ratio for coated devices compared to uncoated controls (p < 0.05).

These results suggest that coating MEAs with an antioxidant can significantly improve their reliability to record neural activity. However, in the chronic phase of neuroinflammation, the effect of the antioxidant on the proportion of active electrodes was not statistically higher than uncoated controls. This suggests that the antioxidant coating may delay the effects of neuronal loss but cannot completely circumvent them. Future studies will evaluate the histological response and markers directly related to oxidative stress to fully assess the antioxidative response.




Acknowledgements (Optional): : This work was supported in part by the National Institutes of Health, National Institute for Neurological Disorders and Stroke (R01NS110823, GRANT12635723, Capadona/Pancrazio) diversity supplement (Hernandez-Reynoso), and the National Institute for Biomedical Imaging and Bioengineering, (T32EB004314, Capadona/Kirsch). Also, this material is based upon work supported by the National Science Foundation Graduate Research Fellowship (Grant No. 1937968, Krebs). Additional support was provided by Merit Review Award (GRANT12418820, Capadona) and a Research Career Scientist Award (GRANT12635707, Capadona) from the United States (US) Department of Veterans Affairs Rehabilitation Research and Development Service. The authors thank Dr. Alexandra Joshi-Imre and Dr. Negar Geramifard for the fabrication of non-functional devices for implantation.


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