Relationship between intracortical electrode design and chronic recording function.

Intracortical electrodes record neural signals directly from local populations of neurons in the brain, and conduct them to external electronics that control prosthetics. However, the relationship between electrode design, defined by shape, size and tethering; and long-term (chronic) stability of the neuron-electrode interface is poorly understood. Here, we studied the effects of various commercially available intracortical electrode designs that vary in shape (cylindrical, planar), size (15 µm, 50 µm and 75 µm), and tethering [electrode connections to connector with (tethered) and without tethering cable (untethered)] using histological, transcriptomic, and electrophysiological analyses over acute (3 day) and chronic (12 week) timepoints. Quantitative analysis of histological sections indicated that Michigan 50 µm (M50) and Michigan tethered (MT) electrodes induced significantly (p < 0.01) higher glial scarring, and lesser survival of neurons in regions of blood-brain barrier (BBB) breach when compared to microwire (MW) and Michigan 15 µm (M15) electrodes acutely and chronically. Gene expression analysis of the neurotoxic cytokines interleukin (Il)1 (Il1α, Il1ß), Il6, Il17 (Il17a, Il17b, Il17f), and tumor necrosis factor alpha (Tnf) indicated that MW electrodes induced significantly (p < 0.05) reduced expression of these transcripts when compared to M15, M50 and FMAA electrodes chronically. Finally, electrophysiological assessment of electrode function indicated that MW electrodes performed significantly (p < 0.05) better than all other electrodes over a period of 12 weeks. These studies reveal that intracortical electrodes with smaller size, cylindrical shape, and without tethering cables produce significantly diminished inflammatory responses when compared to large, planar and tethered electrodes. These studies provide a platform for the rational design and assessment of chronically functional intracortical electrode implants in the future.

The impact of chronic blood-brain barrier breach on intracortical electrode function.

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.