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.

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.

Using evoked compound action potentials to quantify differential neural activation with burst and conventional, 40 Hz spinal cord stimulation in ovines.

Unlike conventional dorsal spinal cord stimulation (SCS)-which uses single pulses at a fixed rate-burst SCS uses a fixed-rate, five-pulse stimuli cluster as a treatment for chronic pain; mechanistic explanations suggest burst SCS differentially modulate the medial and lateral pain pathways vs conventional SCS. Neural activation differences between burst and conventional SCS are quantifiable with the spinal-evoked compound action potential (ECAP), an electrical measure of synchronous neural activation. Methods: We implanted 7 sheep with a dorsal stimulation lead at T9/T10, a dorsal ECAP sensing lead at T6/T7, and a lead also at T9/T10 but adjacent to the anterolateral system (ALS). Both burst and conventional SCS with stimulation amplitudes up to the visual motor threshold (vMT) were delivered to 3 different dorsal spinal locations, and ECAP thresholds (ECAPTs) were calculated for all combinations. Then, changes in ALS activation were assessed with both types of SCS. Results: Evoked compound action potential thresholds and vMTs were significantly higher (P < 0.05) with conventional vs burst SCS, with no statistical difference (P > 0.05) among stimulation sites. However, the vMT-ECAPT window (a proxy for the useable therapeutic dosing range) was significantly wider (P < 0.05) with conventional vs burst SCS. No significant difference (P > 0.05) in ALS activation was noted between conventional and burst SCS. Conclusion: When dosed equivalently, no differentially unique change in ALS activation results with burst SCS vs conventional SCS; in addition, sub-ECAPT burst SCS results in no discernable excitability changes in the neural pathways feeding pain relevant supraspinal sites.

Liquid Crystalline Polymers: Opportunities to Shape Neural Interfaces.

OBJECTIVES: Polymers have emerged as constituent materials for the creation of microscale neural interfaces; however, limitations regarding water permeability, delamination, and material degradation impact polymeric device robustness. Liquid crystal polymers (LCPs) have molecular order like a solid but with the fluidity of a liquid, resulting in a unique material, with properties including low water permeability, chemical inertness, and mechanical toughness. The objective of this article is to review the state-of-the-art regarding the use of LCPs in neural interface applications and discuss challenges and opportunities where this class of materials can advance the field of neural interfaces. MATERIALS AND METHODS: This review article focuses on studies that leverage LCP materials to interface with the nervous system in vivo. A comprehensive literature search was performed using PubMed, Web of Science (Clarivate Analytics), and Google Scholar. RESULTS: There have been recent efforts to create neural interfaces that leverage the material advantages of LCPs. The literature offers examples of LCP as a basis for implantable medical devices and neural interfaces in the form of planar electrode arrays for retinal prosthetic, electrocorticography applications, and cuff-like structures for interfacing the peripheral nerve. In addition, there have been efforts to create penetrating intracortical devices capable of microstimulation and resolution of biopotentials. Recent work with a subclass of LCPs, namely liquid crystal elastomers, demonstrates that it is possible to create devices with features that deploy away from a central implantation site to interface with a volume of tissue while offering the possibility of minimizing tissue damage. CONCLUSION: We envision the creation of novel microscale neural interfaces that leverage the physical properties of LCPs and have the capability of deploying within neural tissue for enhanced integration and performance.

Influence of Implantation Depth on the Performance of Intracortical Probe Recording Sites.

Microelectrode arrays (MEAs) enable the recording of electrical activity from cortical neurons which has implications for basic neuroscience and neuroprosthetic applications. The design space for MEA technology is extremely wide where devices may vary with respect to the number of monolithic shanks as well as placement of microelectrode sites. In the present study, we examine the differences in recording ability between two different MEA configurations: single shank (SS) and multi-shank (MS), both of which consist of 16 recording sites implanted in the rat motor cortex. We observed a significant difference in the proportion of active microelectrode sites over the 8-week indwelling period, in which SS devices exhibited a consistent ability to record activity, in contrast to the MS arrays which showed a marked decrease in activity within 2 weeks post-implantation. Furthermore, this difference was revealed to be dependent on the depth at which the microelectrode sites were located and may be mediated by anatomical heterogeneity, as well as the distribution of inhibitory neurons within the cortical layers. Our results indicate that the implantation depth of microelectrodes within the cortex needs to be considered relative to the chronic performance characterization.

Intracortical Microelectrode Array Unit Yield under Chronic Conditions: A Comparative Evaluation.

While microelectrode arrays (MEAs) offer the promise of elucidating functional neural circuitry and serve as the basis for a cortical neuroprosthesis, the challenge of designing and demonstrating chronically reliable technology remains. Numerous studies report "chronic" data but the actual time spans and performance measures corresponding to the experimental work vary. In this study, we reviewed the experimental durations that constitute chronic studies across a range of MEA types and animal species to gain an understanding of the widespread variability in reported study duration. For rodents, which are the most commonly used animal model in chronic studies, we examined active electrode yield (AEY) for different array types as a means to contextualize the study duration variance, as well as investigate and interpret the performance of custom devices in comparison to conventional MEAs. We observed wide-spread variance within species for the chronic implantation period and an AEY that decayed linearly in rodent models that implanted commercially-available devices. These observations provide a benchmark for comparing the performance of new technologies and highlight the need for consistency in chronic MEA studies. Additionally, to fully derive performance under chronic conditions, the duration of abiotic failure modes, biological processes induced by indwelling probes, and intended application of the device are key determinants.

Mechanically Robust, Softening Shape Memory Polymer Probes for Intracortical Recording.

While intracortical microelectrode arrays (MEAs) may be useful in a variety of basic and clinical scenarios, their implementation is hindered by a variety of factors, many of which are related to the stiff material composition of the device. MEAs are often fabricated from high modulus materials such as silicon, leaving devices vulnerable to brittle fracture and thus complicating device fabrication and handling. For this reason, polymer-based devices are being heavily investigated; however, their implementation is often difficult due to mechanical instability that requires insertion aids during implantation. In this study, we design and fabricate intracortical MEAs from a shape memory polymer (SMP) substrate that remains stiff at room temperature but softens to 20 MPa after implantation, therefore allowing the device to be implanted without aids. We demonstrate chronic recordings and electrochemical measurements for 16 weeks in rat cortex and show that the devices are robust to physical deformation, therefore making them advantageous for surgical implementation.

Deployable, liquid crystal elastomer-based intracortical probes.

Intracortical microelectrode arrays (MEAs) are currently limited in their chronic functionality due partially to the foreign body response (FBR) that develops in regions immediately surrounding the implant (typically within 50-100 µm). Mechanically flexible, polymer-based substrates have recently been explored for MEAs as a way of minimizing the FBR caused by the chronic implantation. Nonetheless, the FBR degrades the ability of the device to record neural activity. We are motivated to develop approaches to deploy multiple recording sites away from the initial site of implantation into regions of tissue outside the FBR zone. Liquid Crystal Elastomers (LCEs) are responsive materials capable of programmable and reversible shape change. These hydrophobic materials are also non-cytotoxic and compatible with photolithography. As such, these responsive materials may be well suited to serve as substrates for smart, implantable electronics. This study explores the feasibility of LCE-based deployable intracortical MEAs. LCE intracortical probes are fabricated on a planar substrate and adopt a 3D shape after being released from the substrate. The LCE probes are then fixed in a planar configuration using polyethylene glycol (PEG). The PEG layer dissolves in physiological conditions, allowing the LCE probe to deploy post-implantation. Critically, we show that LCE intracortical probes will deploy within a brain-like agarose tissue phantom. We also show that deployment distance increases with MEA width. A finite element model was then developed to predict the deformed shape of the deployed probe when embedded in an elastic medium. Finally, LCE-based deployable intracortical MEAs were capable of maintaining electrochemical stability, recording extracellular signals from cortical neurons in vivo, and deploying recording sites greater than 100 µm from the insertion site in vivo. Taken together, these results suggest the feasibility of using LCEs to develop deployable intracortical MEAs. STATEMENT OF SIGNIFICANCE: Deployable MEAs are a recently developed class of neural interfaces that aim to shift the recording sites away from the region of insertion to minimize the negative effects of FBR on the recording performance of MEAs. In this study, we explore LCEs as a potential substrate for deployable MEAs. The novelty of this study lies in the systematic and programmable deployment offered by LCE-based intracortical MEAs. These results illustrate the feasibility and potential application of LCEs as a substrate for deployable intracortical MEAs.

Ruthenium oxide based microelectrode arrays for in vitro and in vivo neural recording and stimulation.

We have characterized the in vitro and in vivo extracellular neural recording and stimulation properties of ruthenium oxide (RuOx) based microelectrodes. Cytotoxicity and functional neurotoxicity assays were carried out to confirm the in vitro biocompatibility of RuOx. Material extract assays, in accordance to ISO protocol "10993-5: Biological evaluation of medical devices", revealed no significant effect on neuronal cell viability or the functional activity of cortical networks. In vitro microelectrode arrays (MEAs), with indium tin oxide (ITO) sites modified with sputtered iridium oxide (IrOx) and RuOx in a single array, were developed for a direct comparison of electrochemical and recording performance of RuOx to ITO and IrOx deposited microelectrode sites. The impedance of the RuOx-coated electrodes measured by electrochemical impedance spectroscopy was notably lower than that of ITO electrodes, resulting in robust extracellular recordings from cortical networks in vitro. We found comparable signal-to-noise ratios (SNRs) for RuOx and IrOx, both significantly higher than the SNR for ITO. RuOx-based MEAs were also fabricated and implanted in the rat motor cortex to demonstrate manufacturability of the RuOx processing and acute recording capabilities in vivo. We observed single-unit extracellular action potentials with a SNR >22, representing a first step for neurophysiological recordings in vivo with RuOx based microelectrodes. STATEMENT OF SIGNIFICANCE: A critical challenge in neural interface technology is the development of microelectrodes that have recording and electrical stimulation capabilities suitable for bidirectional communication between the external electronic device and the nervous system. The present study explores the feasibility and functional capabilities of ruthenium oxide microelectrodes as a neural interface. Significant improvement in electrochemical properties and neuronal recordings are reported when compared to commercially available indium tin oxide and was similar to that of iridium oxide electrodes. The data demonstrate the potential for future development of chronic neural interfaces using ruthenium oxide based microelectrodes for recording and stimulation.

Changes in Electroencephalography Activity in Response to Power Mobility Training: A Pilot Project.

Purpose: The purposes of this pilot project were to examine the impact of power mobility training on (1) electroencephalography (EEG) activity in children with severe cerebral palsy (CP) and (2) power mobility skill acquisition. Method: A single-subject A-B-A-B research design with a 5-week duration for each phase (20 wk total) was replicated across three participants with severe CP (Gross Motor Function Classification System Level V). Data related to the target behaviour, as represented by EEG activity, were collected each week. Power mobility skills were assessed using the Canadian Occupational Performance Measure (COPM), the Wheelchair Skills Checklist (WSC), and the Assessment of Learning Powered mobility use (ALP). Weekly power mobility training was provided during the intervention phases. EEG data were analyzed by means of three measurement metrics (power spectral density, mutual information, and transfer entropy). Results: All three participants demonstrated changes in activation in frontoparietal EEG recordings and clinically significant improvements in power mobility skill acquisition as measured by the COPM as well as by the ALP and WSC. Conclusions: Power mobility training appeared to affect both neuroplastic and skill acquisition. Combining the use of EEG with direct therapist-observation measurement tools may provide a more complete understanding of the impact of power mobility training on children with severe CP.

Objectif : le présent projet pilote vise à examiner les répercussions de l'entraînement à la mobilité motorisée sur 1) l'activité électroencéphalographique (ÉEG) chez les enfants atteints d'une paralysie cérébrale (PC) marquée et 2) l'acquisition d'habiletés à la mobilité motorisée. Méthodologie : les chercheurs ont répliqué une méthodologie de recherche A-B-A-B individuelle d'une durée de cinq semaines par phase (total de 20 semaines) chez trois participants ayant une PC marquée (niveau V du système de classification de la motricité brute). Chaque semaine, ils ont colligé les données relatives au comportement ciblé, représentées par l'activité ÉEG. Ils ont évalué l'habileté à la mobilité motorisée au moyen de la mesure canadienne du rendement occupationnel (MCRO), de la liste des habiletés en fauteuil roulant (LHFR) et de l'évaluation de l'apprentissage d'utilisation de la mobilité motorisée (ÉAUMM). Pendant les phases d'intervention, ils ont fourni un entraînement hebdomadaire à la mobilité motorisée. Ils ont analysé les données d'ÉEG à l'aide de trois mesures de rendement (densité du spectre de puissance, information mutuelle et entropie de transfert). Résultats : les trois participants ont démontré des changements à l'activation des enregistrements ÉEG frontopariétaux et des améliorations cliniquement significatives à l'acquisition des habiletés de mobilité motorisée mesurée par la MCRO, l'ÉAUMM et la LHFR. Conclusion : l'entraînement à la mobilité motorisée semble avoir des effets à la fois sur la plasticité neurale et sur l'acquisition d'habiletés. La combinaison de l'ÉEG avec des outils de mesure observés directement par le thérapeute pourrait permettre de mieux comprendre les répercussions de l'entraînement à la mobilité motorisée chez les enfants ayant une PC marquée.

Chronic Intracortical Recording and Electrochemical Stability of Thiol-ene/Acrylate Shape Memory Polymer Electrode Arrays.

Current intracortical probe technology is limited in clinical implementation due to the short functional lifetime of implanted devices. Devices often fail several months to years post-implantation, likely due to the chronic immune response characterized by glial scarring and neuronal dieback. It has been demonstrated that this neuroinflammatory response is influenced by the mechanical mismatch between stiff devices and the soft brain tissue, spurring interest in the use of softer polymer materials for probe encapsulation. Here, we demonstrate stable recordings and electrochemical properties obtained from fully encapsulated shape memory polymer (SMP) intracortical electrodes implanted in the rat motor cortex for 13 weeks. SMPs are a class of material that exhibit modulus changes when exposed to specific conditions. The formulation used in these devices softens by an order of magnitude after implantation compared to its dry, room-temperature modulus of ~2 GPa.

Diffusion-Weighted Breast Magnetic Resonance Imaging: A Semiautomated Voxel Selection Technique Improves Interreader Reproducibility of Apparent Diffusion Coefficient Measurements.

OBJECTIVE: To determine whether a semiautomated voxel selection technique improves interreader reproducibility for breast apparent diffusion coefficient (ADC) measurements. METHODS: Three readers retrospectively performed ADC measurements of 31 breast lesions (16 malignant, 15 benign) and contralateral normal tissue in 26 women both unassisted (manual method) and assisted by a semiautomated software tool that excludes voxels below a dynamically specified signal intensity threshold. Reproducibility between readers for each technique was assessed by Bland-Altman analysis and concordance correlation coefficients (CCCs). RESULTS: Differences between readers' measured ADCs of lesions were smaller with the semiautomated tool vs the manual method. Concordance correlation coefficients for each reader pair were greater with the semiautomated tool for lesions (mean CCC difference, 0.11; 95% confidence interval, 0.04-0.26). For normal tissue, reader agreement was lower than for lesions and did not differ based on software tools (mean CCC difference, 0.00; 95% confidence interval, -0.14 to 0.13). CONCLUSIONS: A semiautomated voxel selection tool can improve interreader reproducibility of breast lesion ADC measures.