Search Results (31)

The promise of intracortical neural interfaces—to restore lost sensory and motor function and probe the brain’s activity—has long been constrained by device instability over chronic implantation. Conventional silicon-based probes, composed of heterogeneous materials, often fail due to mechanical mismatch, inflammatory responses, and interface-driven degradation, where stress can induce cracking, swelling, and exposure of cytotoxic elements to neural tissue. Silicon carbide (SiC) offers a compelling solution, combining chemical inertness, structural strength, and biocompatibility in both amorphous and crystalline forms. In this review, we discuss advances in SiC neural interfaces, highlighting contributions from multiple laboratories and emphasizing our own work on monolithic devices, constructed entirely from a single, homogeneous SiC material system. These devices mitigate interface-driven failures and show preliminary indications of magnetic resonance imaging (MRI) compatibility, with minimal image artifacts observed compared to conventional silicon probes, though further in vivo studies are needed to confirm thermal safety at high-field conditions. Collectively, SiC establishes a versatile platform for next-generation, durable neural interfaces capable of reliable, long-term brain interaction for both scientific and clinical applications. Full article

Intracortical microelectrode arrays (MEAs) are tools for recording and stimulating neural activity, with potential applications in prosthetic control and treatment of neurological disorders. However, when chronically implanted, the long-term functionality of MEAs is hindered by the foreign body response (FBR), characterized by gliosis, neuronal loss, and the formation of a glial scar encapsulating layer. This response begins immediately after implantation and is exacerbated by factors such as brain micromotion and the mechanical mismatch between stiff electrodes and soft brain tissue, leading to signal degradation. Despite progress in mitigating these issues, the underlying mechanisms of the brain’s response to MEA implantation remain unclear, particularly regarding how cells sense and respond to the associated mechanical forces. Mechanosensitive ion channels, such as the Piezo family, are key mediators of cellular responses to mechanical stimuli. In this study, silicon-based NeuroNexus MEAs consisting of four shanks were implanted in the rat somatosensory cortex for sixteen weeks. Weekly neural recordings were conducted to assess signal quality over time, revealing a decline in active electrode yield and signal amplitude. Immunohistochemical analysis showed an increase in GFAP intensity and decreased neuronal density near the implant site. Furthermore, Piezo1—but not Piezo2—was strongly expressed in GFAP-positive astrocytes within 25 µm of the implant. Piezo2 expression appeared relatively uniform within each brain slice, both in and around the MEA implantation site across cortical layers. Our study builds on previous work by demonstrating a potential role of Piezo1 in the chronic FBR induced by MEA implantation over a 16-week period. Our findings highlight Piezo1 as the primary mechanosensitive channel driving chronic FBR, suggesting it may be a target for improving MEA design and long-term functionality. Full article

This review outlines the technological principles of neural–computer interface (NCI) construction, classifying them according to: (1) the degree of intervention (invasive, semi-invasive, and non-invasive); (2) the direction of signal communication, including BCI (brain–computer interface) for converting neural activity into commands for external devices, CBI (computer–brain interface) for translating artificial signals into stimuli for the CNS, and BBI (brain–brain interface) for direct brain-to-brain interaction systems that account for agency; and (3) the mode of user interaction with technology (active, reactive, passive). For each NCI type, we detail the fundamental data processing principles, covering signal registration, digitization, preprocessing, classification, encoding, command execution, and stimulation, alongside engineering implementations ranging from EEG/MEG to intracortical implants and from transcranial magnetic stimulation (TMS) to intracortical microstimulation (ICMS). We also review mathematical modeling methods for NCIs, focusing on optimizing the extraction of informative features from neural signals—decoding for BCI and encoding for CBI—followed by a discussion of quasi-real-time operation and the use of DSP and neuromorphic chips. Quantitative metrics and rehabilitation measures for evaluating NCI system effectiveness are considered. Finally, we highlight promising future research directions, such as the development of electrochemical interfaces, biomimetic hierarchical systems, and energy-efficient technologies capable of expanding brain functionality. Full article

Background: The rapid expansion of the brain–computer interface for patients with neurological deficits has garnered significant interest, and for patients, it provides an additional route where conventional rehabilitation has its limits. This has particularly been the case for patients who lose the ability to communicate. Circumventing neural injuries by recording from the intact cortex and subcortex has the potential to allow patients to communicate and restore self-expression. Discoveries over the last 10–15 years have been possible through advancements in technology, neuroscience, and computing. By examining studies involving intracranial brain–computer interfaces that aim to restore communication, we aimed to explore the advances made and explore where the technology is heading. Methods: For this scoping review, we systematically searched PubMed and OVID Embase. After processing the articles, the search yielded 41 articles that we included in this review. Results: The articles predominantly assessed patients who had either suffered from amyotrophic lateral sclerosis, cervical cord injury, or brainstem stroke, resulting in tetraplegia and, in some cases, difficulty speaking. Of the intracranial implants, ten had ALS, six had brainstem stroke, and thirteen had a spinal cord injury. Stereoelectroencephalography was also used, but the results, whilst promising, are still in their infancy. Studies involving patients who were moving cursors on a screen could improve the speed of movement by optimising the interface and utilising better decoding methods. In recent years, intracortical devices have been successfully used for accurate speech-to-text and speech-to-audio decoding in patients who are unable to speak. Conclusions: Here, we summarise the progress made by BCIs used for communication. Speech decoding directly from the cortex can provide a novel therapeutic method to restore full, embodied communication to patients suffering from tetraplegia who otherwise cannot communicate. Full article

Micro-electrocorticography (µECoG) electrodes have emerged to balance the trade-off between invasiveness and signal quality in brain recordings. However, its large-scale applicability is still hindered by a lack of comparative studies assessing the relationship between ECoG and traditional recording methods such as penetrating electrodes. This study aimed to compare somatosensory evoked potentials (SEPs) through the lenses of a µECoG and an intracortical microelectrode array (MEA). The electrodes were implanted in the pig’s primary somatosensory cortex, while SEPs were generated by applying electrical stimulation to the ulnar nerve. The SEP amplitude, signal-to-noise ratio (SNR), power spectral density (PSD), and correlation structure were analysed. Overall, SEPs resulting from MEA recordings had higher amplitudes and contained significantly more spectral power, especially at higher frequencies. However, the SNRs were similar between the interfaces. These results demonstrate the feasibility of using µECoG to decode SEPs with wide-range applications in physiology monitoring and brain–computer interfaces. Full article

Purpose: Our aim was to use intracortical recording to enable the tracking of ischemic infarct development over the first few critical hours of ischemia with a high time resolution in pigs. We employed electrophysiological measurements to obtain quick feedback on neural function, which might be useful for screening, e.g., for the optimal dosage and timing of agents prior to further pre-clinical evaluation. Methods: Micro-electrode arrays containing 16 (animal 1) or 32 electrodes (animal 2–7) were implanted in the primary somatosensory cortex of seven female pigs, and continuous electrical stimulation was applied at 0.2 Hz to a cuff electrode implanted on the ulnar nerve. Ischemic stroke was induced after 30 min of baseline recording by injection of endothelin-1 onto the cortex adjacent to the micro-electrode array. Evoked responses were extracted over a moving window of 180 s and averaged across channels as a measure of cortical excitability. Results: Across the animals, the cortical excitability was significantly reduced in all seven 30 min segments following endothelin-1 injection, as compared to the 30 min preceding this intervention. This difference was not explained by changes in the anesthesia, ventilation, end-tidal CO₂, mean blood pressure, heart rate, blood oxygenation, or core temperature, which all remained stable throughout the experiment. Conclusions: The animal model may assist in maturing neuroprotective approaches by testing them in an accessible model of resemblance to human neural and cardiovascular physiology and body size. This would constitute an intermediate step for translating positive results from rodent studies into human application, by more efficiently enabling effective optimization prior to chronic pre-clinical studies in large animals. Full article

(1) Background: Intracortical microelectrodes (IMEs) are an important part of interfacing with the central nervous system (CNS) and recording neural signals. However, recording electrodes have shown a characteristic steady decline in recording performance owing to chronic neuroinflammation. The topography of implanted devices has been explored to mimic the nanoscale three-dimensional architecture of the extracellular matrix. Our previous work used histology to study the implant sites of non-recording probes and showed that a nanoscale topography at the probe surface mitigated the neuroinflammatory response compared to probes with smooth surfaces. Here, we hypothesized that the improvement in the neuroinflammatory response for probes with nanoscale surface topography would extend to improved recording performance. (2) Methods: A novel design modification was implemented on planar silicon-based neural probes by etching nanopatterned grooves (with a 500 nm pitch) into the probe shank. To assess the hypothesis, two groups of rats were implanted with either nanopatterned (n = 6) or smooth control (n = 6) probes, and their recording performance was evaluated over 4 weeks. Postmortem gene expression analysis was performed to compare the neuroinflammatory response from the two groups. (3) Results: Nanopatterned probes demonstrated an increased impedance and noise floor compared to controls. However, the recording performances of the nanopatterned and smooth probes were similar, with active electrode yields for control probes and nanopatterned probes being approximately 50% and 45%, respectively, by 4 weeks post-implantation. Gene expression analysis showed one gene, Sirt1, differentially expressed out of 152 in the panel. (4) Conclusions: this study provides a foundation for investigating novel nanoscale topographies on neural probes. Full article

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. Full article

Intracortical neural probes are both a powerful tool in basic neuroscience studies of brain function and a critical component of brain computer interfaces (BCIs) designed to restore function to paralyzed patients. Intracortical neural probes can be used both to detect neural activity at single unit resolution and to stimulate small populations of neurons with high resolution. Unfortunately, intracortical neural probes tend to fail at chronic timepoints in large part due to the neuroinflammatory response that follows implantation and persistent dwelling in the cortex. Many promising approaches are under development to circumvent the inflammatory response, including the development of less inflammatory materials/device designs and the delivery of antioxidant or anti-inflammatory therapies. Here, we report on our recent efforts to integrate the neuroprotective effects of both a dynamically softening polymer substrate designed to minimize tissue strain and localized drug delivery at the intracortical neural probe/tissue interface through the incorporation of microfluidic channels within the probe. The fabrication process and device design were both optimized with respect to the resulting device mechanical properties, stability, and microfluidic functionality. The optimized devices were successfully able to deliver an antioxidant solution throughout a six-week in vivo rat study. Histological data indicated that a multi-outlet design was most effective at reducing markers of inflammation. The ability to reduce inflammation through a combined approach of drug delivery and soft materials as a platform technology allows future studies to explore additional therapeutics to further enhance intracortical neural probes performance and longevity for clinical applications. Full article

Brain atrophy induced by traumatic brain injury (TBI) progresses in parallel with epileptogenesis over time, and thus accurate placement of intracerebral electrodes to monitor seizure initiation and spread at the chronic postinjury phase is challenging. We evaluated in adult male Sprague Dawley rats whether adjusting atlas-based electrode coordinates on the basis of magnetic resonance imaging (MRI) increases electrode placement accuracy and the effect of chronic electrode implantations on TBI-induced brain atrophy. One group of rats (EEG cohort) was implanted with two intracortical (anterior and posterior) and a hippocampal electrode right after TBI to target coordinates calculated using a rat brain atlas. Another group (MRI cohort) was implanted with the same electrodes, but using T2-weighted MRI to adjust the planned atlas-based 3D coordinates of each electrode. Histological analysis revealed that the anterior cortical electrode was in the cortex in 83% (25% in targeted layer V) of the EEG cohort and 76% (31%) of the MRI cohort. The posterior cortical electrode was in the cortex in 40% of the EEG cohort and 60% of the MRI cohort. Without MRI-guided adjustment of electrode tip coordinates, 58% of the posterior cortical electrodes in the MRI cohort will be in the lesion cavity, as revealed by simulated electrode placement on histological images. The hippocampal electrode was accurately placed in 82% of the EEG cohort and 86% of the MRI cohort. Misplacement of intracortical electrodes related to their rostral shift due to TBI-induced cortical and hippocampal atrophy and caudal retraction of the brain, and was more severe ipsilaterally than contralaterally (p < 0.001). Total lesion area in cortical subfields targeted by the electrodes (primary somatosensory cortex, visual cortex) was similar between cohorts (p > 0.05). MRI-guided adjustment of coordinates for electrodes improved the success rate of intracortical electrode tip placement nearly to that at the acute postinjury phase (68% vs. 62%), particularly in the posterior brain, which exhibited the most severe postinjury atrophy. Overall, MRI-guided electrode implantation improved the quality and interpretation of the origin of EEG-recorded signals. Full article

Intracortical microelectrodes are a critical component of brain-machine interface (BMI) systems. The recording performance of intracortical microelectrodes used for both basic neuroscience research and clinical applications of BMIs decreases over time, limiting the utility of the devices. The neuroinflammatory response to the microelectrode has been identified as a significant contributing factor to its performance. Traditionally, pathological assessment has been limited to a dozen or so known neuroinflammatory proteins, and only a few groups have begun to explore changes in gene expression following microelectrode implantation. Our initial characterization of gene expression profiles of the neuroinflammatory response to mice implanted with non-functional intracortical probes revealed many upregulated genes that could inform future therapeutic targets. Emphasis was placed on the most significant gene expression changes and genes involved in multiple innate immune sets, including Cd14, C3, Itgam, and Irak4. In previous studies, inhibition of Cluster of Differentiation 14 (Cd14) improved microelectrode performance for up to two weeks after electrode implantation, suggesting CD14 can be explored as a potential therapeutic target. However, all measures of improvements in signal quality and electrode performance lost statistical significance after two weeks. Therefore, the current study investigated the expression of genes in the neuroinflammatory pathway at the tissue-microelectrode interface in Cd14^−/− mice to understand better how Cd14 inhibition was connected to temporary improvements in recording quality over the initial 2-weeks post-surgery, allowing for the identification of potential co-therapeutic targets that may work synergistically with or after CD14 inhibition to improve microelectrode performance. Full article

Intracortical microelectrode arrays are used for recording neural signals at single-unit resolution and are promising tools for studying brain function and developing neuroprosthetics. Research is being done to increase the chronic performance and reliability of these probes, which tend to decrease or fail within several months of implantation. Although recording paradigms vary, studies focused on assessing the reliability and performance of these devices often perform recordings under anesthesia. However, anesthetics—such as isoflurane—are known to alter neural activity and electrophysiologic function. Therefore, we compared the neural recording performance under anesthesia (2% isoflurane) followed by awake conditions for probes implanted in the motor cortex of both male and female Sprague-Dawley rats. While the single-unit spike rate was significantly higher by almost 600% under awake compared to anesthetized conditions, we found no difference in the active electrode yield between the two conditions two weeks after surgery. Additionally, the signal-to-noise ratio was greater under anesthesia due to the noise levels being nearly 50% greater in awake recordings, even though there was a 14% increase in the peak-to-peak voltage of distinguished single units when awake. We observe that these findings are similar for chronic time points as well. Our observations indicate that either anesthetized or awake recordings are acceptable for studies assessing the chronic reliability and performance of intracortical microelectrode arrays. Full article

An intracortical visual prosthesis plays a vital role in partially restoring the faculty of sight in visually impaired people. Reliable high date rate wireless links are needed for transcutaneous communication. Such wireless communication should receive stimulation data (downlink) and send out neural recorded data (uplink). Hence, there is a need for an implanted transceiver that is low-power and delivers sufficient data rate for both uplink and downlink. In this paper, we propose an integrated circuit (IC) solution based on impulse radio ultrawideband using on-off keying modulation (OOK IR-UWB) for the uplink transmitter, and binary phase-shift keying (BPSK) with sampling and digital detection for the downlink receiver. To make the solution low-power, predominantly digital components are used in the presented transceiver test-chip. Current-controlled oscillators and an impulse generator provide tunability and complete the on-chip integration. The transceiver test-IC is fabricated in 180 nm CMOS technology and occupies only 0.0272 mm${}^2$. At 1.3 V power supply, only 0.2 mW is consumed for the BPSK receiver and 0.3 mW for the IR-UWB transmitter in the transceiver IC, while delivering 1 Mbps and 50 Mbps, respectively. Our link budget analysis shows that this test chip is suitable for intracortical integration considering the future off-chip antennas/coils transcutaneous 3–7 mm communication with the outer side. Hence, our work will enable realistic wireless links for the intracortical visual prosthesis. Full article

For chronic applications of flexible neural implants, e.g., intracortical probes, the flexible substrate material has to encapsulate the electrical conductors with a long-term stability against the saline environment of the neural tissue. The biocompatible polymer polyimide is often used for this purpose. Due to its chemical inertness, the adhesion between two polyimide layers is, however, a challenge, which can lead to delamination and, finally, to short circuits. The state-of-the-art method to improve the adhesion strength is activating the polyimide surface using oxygen reactive ion etching (O₂ RIE). However, the influence of the process variations (etching time, bias power) on the long-term stability is still unclear. Therefore, we establish a test method, where the aging of a gold interdigital structure embedded in two polyimide layers and immersed in saline solution is accelerated using an elevated temperature, mechanical stress and an electrical field. A continuous measurement of a leakage current is used to define the failure state. The results show that the variation of the O₂ RIE plasma process has a significant effect on the long-term stability of the test samples. Comparing the two different plasma treatments 0.5 min at 25 W and 1 min at 50 W, the long-term stability could be increased from 20.9 ± 19.1 days to 44.9 ± 18.9 days. This corresponds to more than a doubled lifetime. An ideal solution for the delamination problem is still not available; however, the study shows that the fine-tuning of the fabrication processes can improve the long-term stability of chronically implanted neural electrodes. Full article

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. Full article