title: The impact of chronic blood-brain barrier breach on intracortical electrode function.
abstract: Brain-computer interfaces (BCIs) have allowed control of prosthetic limbs in paralyzed patients. Unfortunately, the electrodes of the BCI that interface with the brain only function for a short period of time before the signal quality on these electrodes becomes substantially diminished. To truly realize the potential of BCIs, it is imperative to have electrodes that function chronically. In order to elucidate the physiological determinants of a chronically functional neural interface, we studied the role of the blood-brain barrier (BBB) in electrode function, because it is a key mediator of neuronal hemostasis. We monitored the status of the BBB and the consequences of BBB breach on electrode function using non-invasive imaging, electrophysiology, genomic, and histological analyses. Rats implanted with commercially available intracortical electrodes demonstrated an inverse correlation between electrode performance and BBB breach over a period of 16 weeks. Genomic analysis showed that chronically functional electrodes elicit an enhanced wound healing response. Conversely, in poorly functioning electrodes, chronic BBB breach led to local accumulation of neurotoxic factors and an influx of pro-inflammatory myeloid cells, which negatively affect neuronal health. These findings were further verified in a subset of electrodes with graded electrophysiological performance. In this study, we determine the mechanistic link between intracortical electrode function and failure. Our results indicate that BBB status is a critical physiological determinant of intracortical electrode function and can inform future electrode design and biochemical intervention strategies to enhance the functional longevity of BCIs.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332-0535, USA.
authors.forename: Tarun
authors.initials: T
authors.lastname: Saxena
authors.forename: Lohitash
authors.initials: L
authors.lastname: Karumbaiah
authors.forename: Eric A
authors.initials: EA
authors.lastname: Gaupp
authors.forename: Radhika
authors.initials: R
authors.lastname: Patkar
authors.forename: Ketki
authors.initials: K
authors.lastname: Patil
authors.forename: Martha
authors.initials: M
authors.lastname: Betancur
authors.forename: Garrett B
authors.initials: GB
authors.lastname: Stanley
authors.forename: Ravi V
authors.initials: RV
authors.lastname: Bellamkonda
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology*; D004567:Electrodes, Implanted; D055724:Electrophysiological Phenomena; D007150:Immunohistochemistry; D008297:Male; D008959:Models, Neurological; D022423:Myeloid Cells / Q000473:pathology; D009410:Nerve Degeneration / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing