Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates
Open accessAbstract
OBJECTIVE: Signal attenuation is a major problem facing intracortical sensors for chronic neuroprosthetic applications. Many studies suggest that failure is due to gliosis around the electrode tips, however, mechanical and material causes of failure are often overlooked. The purpose of this study was to investigate the factors contributing to progressive signal decline by using scanning electron microscopy (SEM) to visualize structural changes in chronically implanted arrays and histology to examine the tissue response at corresponding implant sites. APPROACH: We examined eight chronically implanted intracortical microelectrode arrays (MEAs) explanted from non-human primates at times ranging from 37 to 1051 days post-implant. We used SEM, in vivo neural recordings, and histology (GFAP, Iba-1, NeuN). Three MEAs that were never implanted were also imaged as controls. MAIN RESULTS: SEM revealed progressive corrosion of the platinum electrode tips and changes to the underlying silicon. The parylene insulation was prone to cracking and delamination, and in some instances the silicone elastomer also delaminated from the edges of the MEA. Substantial tissue encapsulation was observed and was often seen growing into defects in the platinum and parylene. These material defects became more common as the time in vivo increased. Histology at 37 and 1051 days post-implant showed gliosis, disruption of normal cortical architecture with minimal neuronal loss, and high Iba-1 reactivity, especially within the arachnoid and dura. Electrode tracts were either absent or barely visible in the cortex at 1051 days, but were seen in the fibrotic encapsulation material suggesting that the MEAs were lifted out of the brain. Neural recordings showed a progressive drop in impedance, signal amplitude, and viable channels over time. SIGNIFICANCE: These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does not prevent useful recordings for several years. Progressive meningeal fibrosis encapsulates and lifts MEAs out of the cortex while ongoing foreign body reactions lead to progressive degradation of the materials. Long-term impedance drops are due to the corrosion of platinum, cracking and delamination of parylene, and delamination of silicone elastomer. Oxygen radicals released by cells of the immune system likely mediate the degradation of these materials. Future MEA designs must address these problems through more durable insulation materials, more inert electrode alloys, and pharmacologic suppression of fibroblasts and leukocytes.
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In the CNS, 90% of Utah arrays implanted in non-human primates failed over a 6 year chronic implantation period, with most failures seen within a year of implantation.
“In the CNS, a tissue less exposed to movement than peripheral nerves, a study determined that 90% of Utah arrays implanted in non-human primates failed over a 6 year chronic implantation period, with most of failures seen within a year of implantation (Barrese et al., 2016).”
From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Barrese et al., 2016
Materials and methods reports eight arrays implanted for 37–1051 days, not a six-year observation period. Results §3.7–3.8 say two arrays worked until they were removed at 994 days for other experiments, contrary to the claim that most failed within a year. The paper does not report the claimed 90% failure rate. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredAs implants fail to move together with tissue, compression and sliding along the interface cause damage to surrounding tissue.
“As implants fail to move together with tissue, the compression and sliding along the interface causes damage to the surrounding tissue (Goldstein and Salcman, 1973; Sharp et al., 2009; Barrese et al., 2016).”
From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Barrese et al., 2016
The Introduction and Discussion §4.1 describe meningeal fibrosis lifting arrays out of the cortex and contributing to recording failure. Discussion §4.3 says mechanical failure modes were not clearly observed. Neither those passages nor the additional searches for compression, sliding, and relative implant–tissue movement address the claimed mechanism of damage to surrounding tissue. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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Ecker, M., Joshi-Imre, A., Modi, R., Frewin, C. L., Garcia-Sandoval, A., Maeng, J., Gutierrez-Heredia, G., Pancrazio, J. J., & Voit, W. E. (2019) · Multifunctional Materials · doi:10.1088/2399-7532/aaed58 · Cited by 34 · see citing works
Lamont, C., Grego, T., Nanbakhsh, K., Shah Idil, A., Giagka, V, Vanhoestenberghe, A., Cogan, S., & Donaldson, N. (2021) · Journal of Neural Engineering · doi:10.1088/1741-2552/abf0d6 · Cited by 28 · see citing works
Implantable Device Fabrication and Packaging
Stieglitz, T. (2023) · Handbook of Neuroengineering · doi:10.1007/978-981-16-5540-1_102 · Cited by 7 · see citing works
- Authors
- Barrese, J. C., Aceros, J., & Donoghue, J. P.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- University of North Florida (US)
- Brown University (US)
- Corresponding author
- Barrese, James C
- Venue
- Journal of Neural Engineering
- Publisher
- IOP Publishing
- Published
- 2016-01-29
- Volume
- 13
- Issue
- 2
- Pages
- 026003
- ISSN
- 1741-2552 (ISSN-L)
- 1741-2560
- PMC
- PMC4854331
- OpenAlex
- W2256612106
- Cited by
- 161
- References
- 76
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 12 · 2023: 17 · 2022: 9 · 2021: 25 · 2020: 16 · 2019: 14 · 2018: 22 · 2017: 15 · 2016: 8
- FWCI
- 11.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Neural Engineering (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS025074)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Physical Sciences › Engineering › Biomedical Engineering › Analog and Mixed-Signal Circuit Design
- Keywords
- intracortical microelectrode arrays, signal attenuation, meningeal fibrosis, gliosis, foreign body reaction, electrode encapsulation, non-human primates, oxygen free radicals
- MeSH terms
- Animals, Electrodes, Implanted, Equipment Design, Female, Macaca mulatta, Male, Microelectrodes, Microscopy, Electron, Scanning, Motor Cortex, Primates
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