NeurostimML: a machine learning model for predicting neurostimulation-induced tissue damage.

Objective. The safe delivery of electrical current to neural tissue depends on many factors, yet previous methods for predicting tissue damage rely on only a few stimulation parameters. Here, we report the development of a machine learning approach that could lead to a more reliable method for predicting electrical stimulation-induced tissue damage by incorporating additional stimulation parameters.Approach. A literature search was conducted to build an initial database of tissue response information after electrical stimulation, categorized as either damaging or non-damaging. Subsequently, we used ordinal encoding and random forest for feature selection, and investigated four machine learning models for classification: Logistic Regression, K-nearest Neighbor, Random Forest, and Multilayer Perceptron. Finally, we compared the results of these models against the accuracy of the Shannon equation.Main Results. We compiled a database with 387 unique stimulation parameter combinations collected from 58 independent studies conducted over a period of 47 years, with 195 (51%) categorized as non-damaging and 190 (49%) categorized as damaging. The features selected for building our model with a Random Forest algorithm were: waveform shape, geometric surface area, pulse width, frequency, pulse amplitude, charge per phase, charge density, current density, duty cycle, daily stimulation duration, daily number of pulses delivered, and daily accumulated charge. The Shannon equation yielded an accuracy of 63.9% using akvalue of 1.79. In contrast, the Random Forest algorithm was able to robustly predict whether a set of stimulation parameters was classified as damaging or non-damaging with an accuracy of 88.3%.Significance. This novel Random Forest model can facilitate more informed decision making in the selection of neuromodulation parameters for both research studies and clinical practice. This study represents the first approach to use machine learning in the prediction of stimulation-induced neural tissue damage, and lays the groundwork for neurostimulation driven by machine learning models.

Planar amorphous silicon carbide microelectrode arrays for chronic recording in rat motor cortex.

Chronic implantation of intracortical microelectrode arrays (MEAs) capable of recording from individual neurons can be used for the development of brain-machine interfaces. However, these devices show reduced recording capabilities under chronic conditions due, at least in part, to the brain's foreign body response (FBR). This creates a need for MEAs that can minimize the FBR to possibly enable long-term recording. A potential approach to reduce the FBR is the use of MEAs with reduced cross-sectional geometries. Here, we fabricated 4-shank amorphous silicon carbide (a-SiC) MEAs and implanted them into the motor cortex of seven female Sprague-Dawley rats. Each a-SiC MEA shank was 8 µm thick by 20 µm wide and had sixteen sputtered iridium oxide film (SIROF) electrodes (4 per shank). A-SiC was chosen as the fabrication base for its high chemical stability, good electrical insulation properties, and amenability to thin film fabrication. Electrochemical analysis and neural recordings were performed weekly for 4 months. MEAs were characterized pre-implantation in buffered saline and in vivo using electrochemical impedance spectroscopy and cyclic voltammetry at 50 mV/s and 50,000 mV/s. Neural recordings were analyzed for single unit activity. At the end of the study, animals were sacrificed for immunohistochemical analysis. We observed statistically significant, but small, increases in 1 and 30 kHz impedance values and 50,000 mV/s charge storage capacity over the 16-week implantation period. Slow sweep 50 mV/s CV and 1 Hz impedance did not significantly change over time. Impedance values increased from 11.6 MΩ to 13.5 MΩ at 1 Hz, 1.2 MΩ-2.9 MΩ at 1 kHz, and 0.11 MΩ-0.13 MΩ at 30 kHz over 16 weeks. The median charge storage capacity of the implanted electrodes at 50 mV/s was 58.1 mC/cm2 on week 1 and 55.9 mC/cm2 on week 16, and at 50,000 mV/s, 4.27 mC/cm2 on week 1 and 5.93 mC/cm2 on week 16. Devices were able to record neural activity from 92% of all active channels at the beginning of the study, At the study endpoint, a-SiC devices were still recording single-unit activity on 51% of electrochemically active electrode channels. In addition, we observed that the signal-to-noise ratio experienced a small decline of -0.19 per week. We also classified observed units as fast and slow repolarizing based on the trough-to-peak time. Although the overall presence of single units declined, fast and slow repolarizing units declined at a similar rate. At recording electrode depth, immunohistochemistry showed minimal tissue response to the a-SiC devices, as indicated by statistically insignificant differences in activated glial cell response between implanted brains slices and contralateral sham slices at 150 µm away from the implant location, as evidenced by GFAP staining. NeuN staining revealed the presence of neuronal cell bodies close to the implantation site, again statistically not different from a contralateral sham slice. These results warrant further investigation of a-SiC MEAs for future long-term implantation neural recording studies.

Reactive Amine Functionalized Microelectrode Arrays Provide Short-Term Benefit but Long-Term Detriment to In Vivo Recording Performance.

Intracortical microelectrode arrays (MEAs) are used for recording neural signals. However, indwelling devices result in chronic neuroinflammation, which leads to decreased recording performance through degradation of the device and surrounding tissue. Coating the MEAs with bioactive molecules is being explored to mitigate neuroinflammation. Such approaches often require an intermediate functionalization step such as (3-aminopropyl)triethoxysilane (APTES), which serves as a linker. However, the standalone effect of this intermediate step has not been previously characterized. Here, we investigated the effect of coating MEAs with APTES by comparing APTES-coated to uncoated controls in vivo and ex vivo. First, we measured water contact angles between silicon uncoated and APTES-coated substrates to verify the hydrophilic characteristics of the APTES coating. Next, we implanted MEAs in the motor cortex (M1) of Sprague-Dawley rats with uncoated or APTES-coated devices. We assessed changes in the electrochemical impedance and neural recording performance over a chronic implantation period of 16 weeks. Additionally, histology and bulk gene expression were analyzed to understand further the reactive tissue changes arising from the coating. Results showed that APTES increased the hydrophilicity of the devices and decreased electrochemical impedance at 1 kHz. APTES coatings proved detrimental to the recording performance, as shown by a constant decay up to 16 weeks postimplantation. Bulk gene analysis showed differential changes in gene expression between groups that were inconclusive with regard to the long-term effect on neuronal tissue. Together, these results suggest that APTES coatings are ultimately detrimental to chronic neural recordings. Furthermore, interpretations of studies using APTES as a functionalization step should consider the potential consequences if the final functionalization step is incomplete.

The effect of a Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP) coating on the chronic recording performance of planar silicon intracortical microelectrode arrays.

Intracortical microelectrode arrays (MEAs) are used to record neural activity. However, their implantation initiates a neuroinflammatory cascade, involving the accumulation of reactive oxygen species, leading to interface failure. Here, we coated commercially-available MEAs with Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP), to mitigate oxidative stress. First, we assessed the in vitro cytotoxicity of modified sample substrates. Then, we implanted 36 rats with uncoated, MnTBAP-coated ("Coated"), or (3-Aminopropyl)triethoxysilane (APTES)-coated devices - an intermediate step in the coating process. We assessed electrode performance during the acute (1-5 weeks), sub-chronic (6-11 weeks), and chronic (12-16 weeks) phases after implantation. Three subsets of animals were euthanized at different time points to assess the acute, sub-chronic and chronic immunohistological responses. Results showed that MnTBAP coatings were not cytotoxic in vitro, and their implantation in vivo improved the proportion of electrodes during the sub-chronic and chronic phases; APTES coatings resulted in failure of the neural interface during the chronic phase. In addition, MnTBAP coatings improved the quality of the signal throughout the study and reduced the neuroinflammatory response around the implant as early as two weeks, an effect that remained consistent for months post-implantation. Together, these results suggest that MnTBAP coatings are a potentially useful modification to improve MEA reliability.

NeurostimML: A machine learning model for predicting neurostimulation-induced tissue damage.

Objective: The safe delivery of electrical current to neural tissue depends on many factors, yet previous methods for predicting tissue damage rely on only a few stimulation parameters. Here, we report the development of a machine learning approach that could lead to a more reliable method for predicting electrical stimulation-induced tissue damage by incorporating additional stimulation parameters. Approach: A literature search was conducted to build an initial database of tissue response information after electrical stimulation, categorized as either damaging or non-damaging. Subsequently, we used ordinal encoding and random forest for feature selection, and investigated four machine learning models for classification: Logistic Regression, K-nearest Neighbor, Random Forest, and Multilayer Perceptron. Finally, we compared the results of these models against the accuracy of the Shannon equation. Main Results: We compiled a database with 387 unique stimulation parameter combinations collected from 58 independent studies conducted over a period of 47 years, with 195 (51%) categorized as non-damaging and 190 (49%) categorized as damaging. The features selected for building our model with a Random Forest algorithm were: waveform shape, geometric surface area, pulse width, frequency, pulse amplitude, charge per phase, charge density, current density, duty cycle, daily stimulation duration, daily number of pulses delivered, and daily accumulated charge. The Shannon equation yielded an accuracy of 63.9% using a k value of 1.79. In contrast, the Random Forest algorithm was able to robustly predict whether a set of stimulation parameters was classified as damaging or non-damaging with an accuracy of 88.3%. Significance: This novel Random Forest model can facilitate more informed decision making in the selection of neuromodulation parameters for both research studies and clinical practice. This study represents the first approach to use machine learning in the prediction of stimulation-induced neural tissue damage, and lays the groundwork for neurostimulation driven by machine learning models.

Isolation of the murine Glut1 deficient thalamocortical circuit: wavelet characterization and reverse glucose dependence of low and gamma frequency oscillations.

Glucose represents the principal brain energy source. Thus, not unexpectedly, genetic glucose transporter 1 (Glut1) deficiency (G1D) manifests with encephalopathy. G1D seizures, which constitute a prominent disease manifestation, often prove refractory to medications but may respond to therapeutic diets. These seizures are associated with aberrant thalamocortical oscillations as inferred from human electroencephalography and functional imaging. Mouse electrophysiological recordings indicate that inhibitory neuron failure in thalamus and cortex underlies these abnormalities. This provides the motivation to develop a neural circuit testbed to characterize the mechanisms of thalamocortical synchronization and the effects of known or novel interventions. To this end, we used mouse thalamocortical slices on multielectrode arrays and characterized spontaneous low frequency oscillations and less frequent 30-50 Hz or gamma oscillations under near-physiological bath glucose concentration. Using the cortical recordings from layer IV among other regions recorded, we quantified oscillation epochs via an automated wavelet-based algorithm. This method proved analytically superior to power spectral density, short-time Fourier transform or amplitude-threshold detection. As expected from human observations, increased bath glucose reduced the lower frequency oscillations while augmenting the gamma oscillations, likely reflecting strengthened inhibitory neuron activity, and thus decreasing the low:high frequency ratio (LHR). This approach provides an ex vivo method for the evaluation of mechanisms, fuels, and pharmacological agents in a crucial G1D epileptogenic circuit.

Antioxidant Dimethyl Fumarate Temporarily but Not Chronically Improves Intracortical Microelectrode Performance.

Intracortical microelectrode arrays (MEAs) can be used in a range of applications, from basic neuroscience research to providing an intimate interface with the brain as part of a brain-computer interface (BCI) system aimed at restoring function for people living with neurological disorders or injuries. Unfortunately, MEAs tend to fail prematurely, leading to a loss in functionality for many applications. An important contributing factor in MEA failure is oxidative stress resulting from chronically inflammatory-activated microglia and macrophages releasing reactive oxygen species (ROS) around the implant site. Antioxidants offer a means for mitigating oxidative stress and improving tissue health and MEA performance. Here, we investigate using the clinically available antioxidant dimethyl fumarate (DMF) to reduce the neuroinflammatory response and improve MEA performance in a rat MEA model. Daily treatment of DMF for 16 weeks resulted in a significant improvement in the recording capabilities of MEA devices during the sub-chronic (Weeks 5-11) phase (42% active electrode yield vs. 35% for control). However, these sub-chronic improvements were lost in the chronic implantation phase, as a more exacerbated neuroinflammatory response occurs in DMF-treated animals by 16 weeks post-implantation. Yet, neuroinflammation was indiscriminate between treatment and control groups during the sub-chronic phase. Although worse for chronic use, a temporary improvement (<12 weeks) in MEA performance is meaningful. Providing short-term improvement to MEA devices using DMF can allow for improved use for limited-duration studies. Further efforts should be taken to explore the mechanism behind a worsened neuroinflammatory response at the 16-week time point for DMF-treated animals and assess its usefulness for specific applications.

Isolation of the murine Glut1 deficient thalamocortical circuit: wavelet characterization and reverse glucose dependence of low and gamma frequency oscillations.

Glucose represents the principal brain energy source. Thus, not unexpectedly, genetic glucose transporter 1 (Glut1) deficiency (G1D) manifests with encephalopathy. G1D seizures, which constitute a prominent disease manifestation, often prove refractory to medications but may respond to therapeutic diets. These seizures are associated with aberrant thalamocortical oscillations as inferred from human electroencephalography and functional imaging. Mouse electrophysiological recordings indicate that inhibitory neuron failure in thalamus and cortex underlies these abnormalities. This provides the motivation to develop a neural circuit testbed to characterize the mechanisms of thalamocortical synchronization and the effects of known or novel interventions. To this end, we used mouse thalamocortical slices on multielectrode arrays and characterized spontaneous low frequency oscillations and less frequent 30-50 Hz or gamma oscillations under near-physiological bath glucose concentration. Using the cortical recordings from layer IV, we quantified oscillation epochs via an automated wavelet-based algorithm. This method proved analytically superior to power spectral density, short-time Fourier transform or amplitude-threshold detection. As expected from human observations, increased bath glucose reduced the lower frequency oscillations while augmenting the gamma oscillations, likely reflecting strengthened inhibitory neuron activity. This approach provides an ex vivo method for the evaluation of mechanisms, fuels, and pharmacological agents in a crucial G1D epileptogenic circuit.

Behavioral paradigm for the evaluation of stimulation-evoked somatosensory perception thresholds in rats.

Intracortical microstimulation (ICMS) of the somatosensory cortex via penetrating microelectrode arrays (MEAs) can evoke cutaneous and proprioceptive sensations for restoration of perception in individuals with spinal cord injuries. However, ICMS current amplitudes needed to evoke these sensory percepts tend to change over time following implantation. Animal models have been used to investigate the mechanisms by which these changes occur and aid in the development of new engineering strategies to mitigate such changes. Non-human primates are commonly the animal of choice for investigating ICMS, but ethical concerns exist regarding their use. Rodents are a preferred animal model due to their availability, affordability, and ease of handling, but there are limited choices of behavioral tasks for investigating ICMS. In this study, we investigated the application of an innovative behavioral go/no-go paradigm capable of estimating ICMS-evoked sensory perception thresholds in freely moving rats. We divided animals into two groups, one receiving ICMS and a control group receiving auditory tones. Then, we trained the animals to nose-poke - a well-established behavioral task for rats - following either a suprathreshold ICMS current-controlled pulse train or frequency-controlled auditory tone. Animals received a sugar pellet reward when nose-poking correctly. When nose-poking incorrectly, animals received a mild air puff. After animals became proficient in this task, as defined by accuracy, precision, and other performance metrics, they continued to the next phase for perception threshold detection, where we varied the ICMS amplitude using a modified staircase method. Finally, we used non-linear regression to estimate perception thresholds. Results indicated that our behavioral protocol could estimate ICMS perception thresholds based on ~95% accuracy of rat nose-poke responses to the conditioned stimulus. This behavioral paradigm provides a robust methodology for evaluating stimulation-evoked somatosensory percepts in rats comparable to the evaluation of auditory percepts. In future studies, this validated methodology can be used to study the performance of novel MEA device technologies on ICMS-evoked perception threshold stability using freely moving rats or to investigate information processing principles in neural circuits related to sensory perception discrimination.

Direct laser writing of 3D electrodes on flexible substrates.

This report describes a 3D microelectrode array integrated on a thin-film flexible cable for neural recording in small animals. The fabrication process combines traditional silicon thin-film processing techniques and direct laser writing of 3D structures at micron resolution via two-photon lithography. Direct laser-writing of 3D-printed electrodes has been described before, but this report is the first to provide a method for producing high-aspect-ratio structures. One prototype, a 16-channel array with 300 µm pitch, demonstrates successful electrophysiological signal capture from bird and mouse brains. Additional devices include 90 µm pitch arrays, biomimetic mosquito needles that penetrate through the dura of birds, and porous electrodes with enhanced surface area. The rapid 3D printing and wafer-scale methods described here will enable efficient device fabrication and new studies examining the relationship between electrode geometry and electrode performance. Applications include small animal models, nerve interfaces, retinal implants, and other devices requiring compact, high-density 3D electrodes.

Behavioral Paradigm for the Evaluation of Stimulation-Evoked Somatosensory Perception Thresholds in Rats.

Intracortical microstimulation (ICMS) of the somatosensory cortex via penetrating microelectrode arrays (MEAs) can evoke cutaneous and proprioceptive sensations for restoration of perception in individuals with spinal cord injuries. However, ICMS current amplitudes needed to evoke these sensory percepts tend to change over time following implantation. Animal models have been used to investigate the mechanisms by which these changes occur and aid in the development of new engineering strategies to mitigate such changes. Non-human primates are commonly the animal of choice for investigating ICMS, but ethical concerns exist regarding their use. Rodents are a preferred animal model due to their availability, affordability, and ease of handling, but there are limited choices of behavioral tasks for investigating ICMS. In this study, we investigated the application of an innovative behavioral go/no-go paradigm capable of estimating ICMS-evoked sensory perception thresholds in freely moving rats. We divided animals into two groups, one receiving ICMS and a control group receiving auditory tones. Then, we trained the animals to nose-poke - a well-established behavioral task for rats - following either a suprathreshold ICMS current-controlled pulse train or frequency-controlled auditory tone. Animals received a sugar pellet reward when nose-poking correctly. When nose-poking incorrectly, animals received a mild air puff. After animals became proficient in this task, as defined by accuracy, precision, and other performance metrics, they continued to the next phase for perception threshold detection, where we varied the ICMS amplitude using a modified staircase method. Finally, we used non-linear regression to estimate perception thresholds. Results indicated that our behavioral protocol could estimate ICMS perception thresholds based on ∼95% accuracy of rat nose-poke responses to the conditioned stimulus. This behavioral paradigm provides a robust methodology for evaluating stimulation-evoked somatosensory percepts in rats comparable to the evaluation of auditory percepts. In future studies, this validated methodology can be used to study the performance of novel MEA device technologies on ICMS-evoked perception threshold stability using freely moving rats or to investigate information processing principles in neural circuits related to sensory perception discrimination.

Chronic Stability of Local Field Potentials Using Amorphous Silicon Carbide Microelectrode Arrays Implanted in the Rat Motor Cortex.

Implantable microelectrode arrays (MEAs) enable the recording of electrical activity of cortical neurons, allowing the development of brain-machine interfaces. However, MEAs show reduced recording capabilities under chronic conditions, prompting the development of novel MEAs that can improve long-term performance. Conventional planar, silicon-based devices and ultra-thin amorphous silicon carbide (a-SiC) MEAs were implanted in the motor cortex of female Sprague-Dawley rats, and weekly anesthetized recordings were made for 16 weeks after implantation. The spectral density and bandpower between 1 and 500 Hz of recordings were compared over the implantation period for both device types. Initially, the bandpower of the a-SiC devices and standard MEAs was comparable. However, the standard MEAs showed a consistent decline in both bandpower and power spectral density throughout the 16 weeks post-implantation, whereas the a-SiC MEAs showed substantially more stable performance. These differences in bandpower and spectral density between standard and a-SiC MEAs were statistically significant from week 6 post-implantation until the end of the study at 16 weeks. These results support the use of ultra-thin a-SiC MEAs to develop chronic, reliable brain-machine interfaces.

A Novel 3D Helical Microelectrode Array for In Vitro Extracellular Action Potential Recording.

Recent advances in cell and tissue engineering have enabled long-term three-dimensional (3D) in vitro cultures of human-derived neuronal tissues. Analogous two-dimensional (2D) tissue cultures have been used for decades in combination with substrate integrated microelectrode arrays (MEA) for pharmacological and toxicological assessments. While the phenotypic and cytoarchitectural arguments for 3D culture are clear, 3D MEA technologies are presently inadequate. This is mostly due to the technical challenge of creating vertical electrical conduction paths (or 'traces') using standardized biocompatible materials and fabrication techniques. Here, we have circumvented that challenge by designing and fabricating a novel helical 3D MEA comprised of polyimide, amorphous silicon carbide (a-SiC), gold/titanium, and sputtered iridium oxide films (SIROF). Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) testing confirmed fully-fabricated MEAs should be capable of recording extracellular action potentials (EAPs) with high signal-to-noise ratios (SNR). We then seeded induced pluripotent stems cell (iPSC) sensory neurons (SNs) in a 3D collagen-based hydrogel integrated with the helical MEAs and recorded EAPs for up to 28 days in vitro from across the MEA volume. Importantly, this highly adaptable design does not intrinsically limit cell/tissue type, channel count, height, or total volume.

Recording of pig neuronal activity in the comparative context of the awake human brain.

Gyriform mammals display neurophysiological and neural network activity that other species exhibit only in rudimentary or dissimilar form. However, neural recordings from large mammals such as the pig can be anatomically hindered and pharmacologically suppressed by anesthetics. This curtails comparative inferences. To mitigate these limitations, we set out to modify electrocorticography, intracerebral depth and intracortical recording methods to study the anesthetized pig. In the process, we found that common forms of infused anesthesia such as pentobarbital or midazolam can be neurophysiologic suppressants acting in dose-independent fashion relative to anesthetic dose or brain concentration. Further, we corroborated that standard laboratory conditions may impose electrical interference with specific neural signals. We thus aimed to safeguard neural network integrity and recording fidelity by developing surgical, anesthesia and noise reduction methods and by working inside a newly designed Faraday cage, and evaluated this from the point of view of neurophysiological power spectral density and coherence analyses. We also utilized novel silicon carbide electrodes to minimize mechanical disruption of single-neuron activity. These methods allowed for the preservation of native neurophysiological activity for several hours. Pig electrocorticography recordings were essentially indistinguishable from awake human recordings except for the small segment of electrical activity associated with vision in conscious persons. In addition, single-neuron and paired-pulse stimulation recordings were feasible simultaneously with electrocorticography and depth electrode recordings. The spontaneous and stimulus-elicited neuronal activities thus surveyed can be recorded with a degree of precision similar to that achievable in rodent or any other animal studies and prove as informative as unperturbed human electrocorticography.

Chronic stability of activated iridium oxide film voltage transients from wireless floating microelectrode arrays.

Successful monitoring of the condition of stimulation electrodes is critical for maintaining chronic device performance for neural stimulation. As part of pre-clinical safety testing in preparation for a visual prostheses clinical trial, we evaluated the stability of the implantable devices and stimulation electrodes using a combination of current pulsing in saline and in canine visual cortex. Specifically, in saline we monitored the stability and performance of 3000 µm2 geometric surface area activated iridium oxide film (AIROF) electrodes within a wireless floating microelectrode array (WFMA) by measuring the voltage transient (VT) response through reverse telemetry. Eight WFMAs were assessed in vitro for 24 days, where n = 4 were pulsed continuously at 80 µA (16 nC/phase) and n = 4 remained in solution with no applied stimulation. Subsequently, twelve different WFMAs were implanted in visual cortex in n = 3 canine subjects (4 WFMAs each). After a 2-week recovery period, half of the electrodes in each of the twelve devices were pulsed continuously for 24 h at either 20, 40, 63, or 80 µA (200 µs pulse width, 100 Hz). VTs were recorded to track changes in the electrodes at set time intervals in both the saline and in vivo study. The VT response of AIROF electrodes remained stable during pulsing in saline over 24 days. Electrode polarization and driving voltage changed by less than 200 mV on average. The AIROF electrodes also maintained consistent performance, overall, during 24 h of pulsing in vivo. Four of the in vivo WFMA devices showed a change in polarization, access voltage, or driving voltage over time. However, no VT recordings indicated electrode failure, and the same trend was typically seen in both pulsed and unpulsed electrodes within the same device. Overall, accelerated stimulation testing in saline and in vivo indicated that AIROF electrodes in the WFMA were able to consistently deliver up to 16 nC per pulse and would be suitable for chronic clinical use.

Tools for Surface Treatment of Silicon Planar Intracortical Microelectrodes.

Intracortical microelectrodes hold great therapeutic potential. But they are challenged with significant performance reduction after modest implantation durations. A substantial contributor to the observed decline is the damage to the neural tissue proximal to the implant and subsequent neuroinflammatory response. Efforts to improve device longevity include chemical modifications or coating applications to the device surface to improve the tissue response. Development of such surface treatments is typically completed using non-functional "dummy" probes that lack the electrical components required for the intended application. Translation to functional devices requires additional consideration given the fragility of intracortical microelectrode arrays. Handling tools greatly facilitate surface treatments to assembled devices, particularly for modifications that require long procedural times. The handling tools described here are used for surface treatments applied via gas-phase deposition and aqueous solution exposure. Characterization of the coating is performed using ellipsometry and x-ray photoelectron spectroscopy. A comparison of electrical impedance spectroscopy recordings before and after the coating procedure on functional devices confirmed device integrity following modification. The described tools can be readily adapted for alternative electrode devices and treatment methods that maintain chemical compatibility.

Wireless transmission of voltage transients from a chronically implanted neural stimulation device.

Objective.Consistent transmission of data from wireless neural devices is critical for monitoring the condition and performance of stimulation electrodes. To date, no wireless neural interface has demonstrated the ability to monitor the integrity of chronically implanted electrodes through wireless data transmission.Approach.In this work, we present a method for wirelessly recording the voltage transient (VT) response to constant-current, cathodic-first asymmetric pulsing from a microelectrode array. We implanted six wireless devices in rat sciatic nerve and wirelessly recorded VT measurements throughout a 38 week implantation period.Main results.Electrode maximum cathodic potential excursion (Emc), access voltage, and driving voltage (extracted from each VT) remained stable throughout the 38 week study period. Average Emc(from an applied +0.6 V interpulse bias) in response to 4.7µA, 200.2µs pulses was 267 ± 107 mV at week 1 post-implantation and 282 ± 52 mV at week 38 post-implantation. Access voltage for the same 4.7µA pulsing amplitude was 239 ± 65 mV at week 1 post-implantation and 268 ± 139 mV at week 38 post-implantation.Significance.The VT response recorded via reverse telemetry from the wireless microelectrode array did not significantly change over a 38 week implantation period and was similar to previously reported VTs from wired microelectrodes with the same geometry. Additionally, the VT response recorded wirelessly in phosphate buffered saline before and after device implantation appeared as expected, showing significantly less electrode polarization and smaller access voltage than the VT responsein vivo.

Insertion mechanics of amorphous SiC ultra-micro scale neural probes.

Objective. Trauma induced by the insertion of microelectrodes into cortical neural tissue is a significant problem. Further, micromotion and mechanical mismatch between microelectrode probes and neural tissue is implicated in an adverse foreign body response (FBR). Hence, intracortical ultra-microelectrode probes have been proposed as alternatives that minimize this FBR. However, significant challenges in implanting these flexible probes remain. We investigated the insertion mechanics of amorphous silicon carbide (a-SiC) probes with a view to defining probe geometries that can be inserted into cortex without buckling.Approach. We determined the critical buckling force of a-SiC probes as a function of probe geometry and then characterized the buckling behavior of these probes by measuring force-displacement responses during insertion into agarose gel and rat cortex.Main results.Insertion forces for a range of probe geometries were determined and compared with critical buckling forces to establish geometries that should avoid buckling during implantation into brain. The studies show that slower insertion speeds reduce the maximum insertion force for single-shank probes but increase cortical dimpling during insertion of multi-shank probes.Significance.Our results provide a guide for selecting probe geometries and insertion speeds that allow unaided implantation of probes into rat cortex. The design approach is applicable to other animal models where insertion of intracortical probes to a depth of 2 mm is required.