title: Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates.
abstract: 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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurological Surgery, New Jersey Medical School, Rutgers University, Newark, NJ, USA. Department of Neuroscience and Brown Institute for Brain Science, Brown University, Providence, RI, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Barrese
authors.forename: Juan
authors.initials: J
authors.lastname: Aceros
authors.forename: John P
authors.initials: JP
authors.lastname: Donoghue
mesh_terms: D000818:Animals; D004567:Electrodes, Implanted / Q000592:standards; D004867:Equipment Design / Q000379:methods* / Q000592:standards; D005260:Female; D008253:Macaca mulatta; D008297:Male; D008839:Microelectrodes / Q000592:standards; D008855:Microscopy, Electron, Scanning / Q000379:methods* / Q000592:standards; D009044:Motor Cortex / Q000502:physiology*; D011323:Primates
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