Electrical signals recorded from neurons by intracortical electrodes have been used by human patients to communicate with computers and to control robotic limbs. The signal quality and the length of time that useful signals can be recorded are inconsistent. The consensus view of the community is that the inflammatory response to the microelectrode contributes, at least in part, to electrode reliability. Inflammation is initiated when inflammatory cells recognize foreign biologics (i.e. damaged/infiltrating proteins and cells). Serum proteins and blood-derived cells invade the central nervous system following microelectrode implantation. Cells and tissue are damaged from the trauma of microelectrode implantation. At the microelectrode surface, accumulation of pro-inflammatory molecules causes neuronal degeneration and increases the permeability of the blood-brain barrier, self- perpetuating the process. We have shown that oxidative stress is a key component of the neuroinflammatory response to microelectrodes and that oxidative stress correlates with neuron viability. In parallel, we and others have shown that the neuroinflammatory response to intracortical microelectrodes directly relates to the instability of neural recordings. Most importantly, we have shown that initial administration of resveratrol, a naturally-derived anti-oxidant, temporally reduces microelectrode-mediated oxidative stress, preserves neuron viability, and facilitates stable neural recordings. Therefore, our central hypothesis is that maintained administration of resveratrol will improve the long-term quality and stability of neural recordings obtained from intracortical microelectrodes. We propose to first quantify to what degree, the anti-oxidant, resveratrol, can improve the longevity and quality of intracortical microelectrode neural recordings. Next, to maximize clinical impact, we will examine two key questions: 1) Can subjects already implanted with microelectrodes demonstrate remediation of neural recordings after the quality and stability of the records has already declined? And 2) How long does a patient need to remain on resveratrol in order to obtain lasting functional outcomes? Throughout the proposed study, resveratrol-treated animals will be evaluated against diluent-treated controls for the longevity and quality of obtained neural recordings defined by the number of active channels and their signal-to-noise ratio, over time. Further, post-mortem histology will correlate recording performance to oxidative stress, neuroprotection and blood-brain barrier stability. This study is designed to answer clinically-relevant questions, and has the potential to directly impact ongoing and future non-human primate and clinical trials by the completion of the proposed study.
Intracortical microelectrodes are the interface within the brain for Brain-Machine Interface technologies. Brain- Machine Interfaces allow one to use one's volitionally-controlled thoughts to control an external device, be it a computer cursor, a robotic arm, or one's own muscles. The majority of research to create a reliable brain machine interface has been directed at those that are severely paralyzed and 'locked-in'. Specifically, those with spinal cord injury, stroke, and Amyotrophic Lateral Sclerosis (ALS) would gain the most. An increasing percentage of these patients are veterans. In the first year after a high tetraplegia injury the average expenses are about $1M and the lifetime expected costs are between $2.4M and $4.4M. Brain computer interfaces have the potential to enable these individuals to utilize many more useful assistive devices, and improve the quality of life for a wide spectrum of disabled Veterans. If microelectrodes were to function for longer durations, the technology could be applied to many other neurological diseases and disorders.
