For nearly 55 years, tungsten microwires have been widely used in neurophysiological experiments in animal models to chronically record neuronal activity. While tungsten microwires initially provide stable recordings, their inability to reliably record high-quality neural signals for tens of years has limited their efficacy for neuroprosthetic applications in humans. Comprehensive understanding of the mechanisms of electrode performance and failure is necessary for developing next generation neural interfaces for humans. In this study, we evaluated the abiotic (electrophysiology, impedance, electrode morphology) and biotic (microglial reactivity, blood-brain barrier disruption, biochemical markers of axonal injury) effects of 16-channel, 50 µm diameter, polyimide insulated tungsten microwires array for implant durations that ranged from acute to up to 9 months in 25 rats. Daily electrode impedance spectroscopy, electrophysiological recordings, blood and cerebrospinal fluid (CSF) withdrawals, and histopathological analysis were performed to study the time-varying effects of chronic electrode implantation. Structural changes at the electrode recording site were observed as early as within 2-3 h of electrode insertion. Abiotic analysis indicated the first 2-3 weeks following surgery was the most dynamic period in the chronic electrode lifetime as there were greater variations in the electrode impedance, functional electrode performance, and the structural changes occurring at the electrode recording tips. Electrode recording site deterioration continued for the long-term chronic animals as insulation damage occurred and recording surface became more recessed over time. In general, electrode impedance and functional performance had smaller daily variations combined with reduced electrode recording site changes during the chronic phase. Histopathological studies were focused largely on characterizing microglial cell responses to electrode implantation. We found that activated microglia were present near the electrode tracks in all non-acute animals studied, thus indicating presence of a neuroinflammatory response regardless of post-implantation survival times and electrode performance. Conversely, dystrophic microglia detectable as fragmented cells were found almost exclusively in acute animals surviving only few hours after implantation. While there was no consistent relationship between microglial cell responses and electrode performance, we noticed co-occurrence of high ferritin expression, intraparenchymal bleeding, and microglial degeneration suggesting presence of excessive oxidative stress via Fenton chemistry. Biochemical analysis indicated that these electrodes always caused a persistent release of axonal injury biomarkers even several months after implantation suggesting persistent tissue damage. Our study suggests that mechanisms of electrode failure are multi-factorial involving both abiotic and biotic parameters. Since these failure modes occur concurrently and cannot be isolated from one another, the lac...

Pt/Ir electrodes have been extensively used in neurophysiology research in recent years as they provide a more inert recording surface as compared to tungsten or stainless steel. While floating microelectrode arrays (FMA) consisting of Pt/Ir electrodes are an option for neuroprosthetic applications, long-term in vivo functional performance characterization of these FMAs is lacking. In this study, we have performed comprehensive abiotic-biotic characterization of Pt/Ir arrays in 12 rats with implant periods ranging from 1 week up to 6 months. Each of the FMAs consisted of 16-channel, 1.5 mm long, and 75 μm diameter microwires with tapered tips that were implanted into the somatosensory cortex. Abiotic characterization included (1) pre-implant and post-explant scanning electron microscopy (SEM) to study recording site changes, insulation delamination and cracking, and (2) chronic in vivo electrode impedance spectroscopy. Biotic characterization included study of microglial responses using a panel of antibodies, such as Iba1, ED1, and anti-ferritin, the latter being indicative of blood-brain barrier (BBB) disruption. Significant structural variation was observed pre-implantation among the arrays in the form of irregular insulation, cracks in insulation/recording surface, and insulation delamination. We observed delamination and cracking of insulation in almost all electrodes post-implantation. These changes altered the electrochemical surface area of the electrodes and resulted in declining impedance over the long-term due to formation of electrical leakage pathways. In general, the decline in impedance corresponded with poor electrode functional performance, which was quantified via electrode yield. Our abiotic results suggest that manufacturing variability and insulation material as an important factor contributing to electrode failure. Biotic results show that electrode performance was not correlated with microglial activation (neuroinflammation) as we were able to observe poor performance in the absence of neuroinflammation, as well as good performance in the presence of neuroinflammation. One biotic change that correlated well with poor electrode performance was intraparenchymal bleeding, which was evident macroscopically in some rats and presented microscopically by intense ferritin immunoreactivity in microglia/macrophages. Thus, we currently consider intraparenchymal bleeding, suboptimal electrode fabrication, and insulation delamination as the major factors contributing toward electrode failure.

Long-term acquisition of high-quality neural recordings is a cornerstone of neuroprosthetic system design. Mitigating the experimental variability of chronically implanted arrays has been a formidable task because the sensor recording sites can be influenced by biotic and abiotic responses. Several studies have implicated changes in electrical interface impedance as a preliminary marker to infer electrode viability. Microelectrode impedance plays an important role in the monitoring of low amplitude and high-resolution extracellular neural signals. In this work, we seek to quantify long-term microelectrode array functionality and derive an impedance-based predictor for electrode functionality that correlates the recording site electrical properties with the functional neuronal recordings in vivo. High temporal resolution metrics of this type would allow one to assess, predict, and improve electrode performance in the future. In a large cohort of animals, we performed daily impedance measurements and neural signal recordings over long periods (up to 21 weeks) of time in rats using tungsten microwire arrays implanted into the somatosensory cortex. This study revealed that there was a time-varying trend in the modulation of impedance that was related to electrode performance. Single units were best detected from electrodes at time points when the electrode entered into the 40-150 KΩ impedance range. This impedance trend was modeled across the full cohort of animals to predict future electrode performance. The model was tested on data from all animals and was able to provide predictions of electrode performance chronically. Insight from this study can be combined with knowledge of electrode materials and histological analysis to provide a more comprehensive predictive model of electrode failure in the future.

This study demonstrated a decoding network for BMI that involved a convolutional and recurrent neural network model. It integrated the feature extraction pipeline into the convolution and pooling layer and used LSTM layer to capture the state transitions. The discussed network eliminated the need to separately train the model at each step in the decoding pipeline. The whole system can be jointly optimized using stochastic gradient descent and is capable of online learning.

In this investigation, the size-scale in mechanical properties of individual [0001] ZnO nanowires and the correlation with atomic-scale arrangements were explored via in situ high-resolution transmission electron microscopy (TEM) equipped with atomic force microscopy (AFM) and nanoindentation (NI) systems. The Young's modulus was determined to be size-scale-dependent for nanowires with diameter, d, in the range of 40 nm ≤ d ≤ 110 nm, and reached the maximum of ∼ 249 GPa for d = 40 nm. However, this phenomenon was not observed for nanowires in the range of 200 nm ≤ d ≤ 400 nm, where an average constant Young's modulus of ∼ 147.3 GPa was detected, close to the modulus value of bulk ZnO. A size-scale dependence in the failure of nanowires was also observed. The thick ZnO nanowires (d ≥ 200 nm) were brittle, while the thin nanowires (d ≤ 110 nm) were highly flexible. The diameter effect and enhanced Young's modulus observed in thin ZnO nanowires are due to the combined effects of surface relaxation and long-range interactions present in ionic crystals, which leads to much stiffer surfaces than bulk wires. The brittle failure in thicker ZnO wires was initiated from the outermost layer, where the maximum tensile stress operates and propagates along the (0001) planes. After a number of loading and unloading cycles, the highly compressed region of the thinner nanowires was transformed from a crystalline to an amorphous phase, and the region near the neutral zone was converted into a mixture of disordered atomic planes and bent lattice fringes as revealed by high-resolution images.