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Types of connectors used across this study arranged according to their history of use. (a) Initial Microtech connector with 12 pins. (b) Winchester style connector with 34 pins. (c) Tulip connector with 40 pins. (d) Current CerePort connector with 100 functional contact pads.
Source publication
Objective:
Brain-computer interfaces (BCIs) using chronically implanted intracortical microelectrode arrays (MEAs) have the potential to restore lost function to people with disabilities if they work reliably for years. Current sensors fail to provide reliably useful signals over extended periods of time for reasons that are not clear. This study...
Contexts in source publication
Context 1
... availability of compact connectors suitable for monkeys with high pin density and low insertion forces was a limiting factor for nearly a decade. Connector design evolved over the time period covered, beginning with a 12-pin Microtech (FR-12S-6; Microtech, Pittsburgh, PA, USA) connector (9 arrays), to a 50-pin Winchester connector (7 arrays), to a 40-pin 'Tulip' connector (9 arrays), and eventually to a zero insertion force, spring-loaded 96-pin connector in a titanium pedestal made by BRMS ( figure 3) in the 53 implants since 2002. ...
Context 2
... acute material failures were from 'shorting' of the connector, as revealed by impedances <50 k on all channels (which is indicative of a path to ground). All of these arrays had the Tulip style connector (see figure 3(c)), which was fabricated from a computer edge-connector card that seemed to be prone to poor or shorted connections. Two cases followed an event in which the gold edge connectors were exposed to saline washes during revision surgeries for head-posts. ...
Similar publications
Brain Computer Interfaces (BCIs) offer significant hope to tetraplegic and paraplegic individuals. This technology relies on extracting and translating motor intent to facilitate control of a computer cursor or to enable fine control of an external assistive device such as a prosthetic limb. Intracortical recording interfaces (IRIs) are critical co...
In order for brain-computer interface (BCI) systems to maximize functionality, users will need to be able to accurately modulate grasp force to avoid dropping heavy objects while also being able to handle fragile items. We present a case-study consisting of two experiments designed to identify whether intracortical recordings from the motor cortex...
Citations
... Diamond also does not trigger inflammatory responses and has no natural oxides, a property that few other non-toxic materials share. Typical implant materials such as silicon, polyimide and parylene only share some of these properties, which impacts their performance over time [5,8,[14][15][16][17]. ...
This paper demonstrates, for the first time, the stability of synthetic diamond as a passive layer within neural implants. Leveraging the exceptional biocompatibility of intrinsic nanocrystalline diamond, a comprehensive review of material aging analysis in the context of in-vivo implants is provided. This work is based on electric impedance monitoring through the formulation of an analytical model that scrutinizes essential parameters such as the deposited metal resistivity, insulation between conductors, changes in electrode geometry, and leakage currents. The evolution of these parameters takes place over an equivalent period of approximately 10 years. The analytical model, focusing on a fractional capacitor, provides nuanced insights into the surface conductivity variation. A comparative study is performed between a classical polymer material (SU8) and synthetic diamond. Samples subjected to dynamic impedance analysis reveal distinctive patterns over time, characterized by their physical degradation. The results highlight the very high stability of diamond, suggesting promise for the electrode’s enduring viability. To support this analysis, microscopic and optical measurements conclude the paper and confirm the high stability of diamond and its strong potential as a material for neural implants with long-life use.
... The microelectrode arrays used in this study were purchased from Blackrock Microsystems (Salt Lake City, UT). The array, referred to as the Utah Electrode Array (UEA) had a 4×4 rectangular grid of 1 mm long microelectrode shafts spaced 400 μm apart ( Figure 2A) and was similar in overall design to the 10×10 microelectrode recording arrays used in several nonhuman primate studies (Santhanam et al., 2006;Barrese et al., 2013) and several clinical studies (Hochberg et al., 2006;Simeral et al., 2011;Hochberg et al., 2012;Collinger et al., 2013;Ajiboye et al., 2017). The wiring diagram relating connector pins to the locations of each microelectrode recording tip in each array was supplied by the manufacturer to allow correlation of end-point histology with recording performance analysis. ...
... We observed a significant amount of connective tissue underneath the base and on the upper parts of the microelectrode shafts of the retrieved arrays. This observation also was reported in cortically implanted UEAs in younger rats (Nolta et al., 2015;Black et al., 2018;Cody et al., 2018) and in UEAs explanted from non-human primates after long indwelling periods (Barrese et al., 2013). Connective tissue was present on all explanted arrays in the older cohort. ...
... Our results suggest that functional issues related to anchorage of the array may be underappreciated. Fibrotic tissue buildup has been proposed to cause movement of multi-shaft recording arrays following implantation injury for free floating arrays in nonhuman primates (Barrese et al., 2013) and cats (Rousche and Normann, 1998;Maynard et al., 2000;McCreery et al., 2010). In a retrospective analysis of numerous experiments with UEAs chronically implanted in macaques, the authors determined that 53% of all slowly-progressing recording failures were due to fibrotic tissue buildup that dramatically changed the orientation of the arrays from their original implantation position (Barrese et al., 2013). ...
Introduction
Available evidence suggests that as we age, our brain and immune system undergo changes that increase our susceptibility to injury, inflammation, and neurodegeneration. Since a significant portion of the potential patients treated with a microelectrode-based implant may be older, it is important to understand the recording performance of such devices in an aged population.
Methods
We studied the chronic recording performance and the foreign body response (FBR) to a clinically used microelectrode array implanted in the cortex of 18-month-old Sprague Dawley rats.
Results and discussion
To the best of our knowledge, this is the first preclinical study of its type in the older mammalian brain. Here, we show that single-unit recording performance was initially robust then gradually declined over a 12-week period, similar to what has been previously reported using younger adult rats and in clinical trials. In addition, we show that FBR biomarker distribution was similar to what has been previously described for younger adult rats implanted with multi-shank recording arrays in the motor cortex. Using a quantitative immunohistochemcal approach, we observed that the extent of astrogliosis and tissue loss near the recording zone was inversely related to recording performance. A comparison of recording performance with a younger cohort supports the notion that aging, in and of itself, is not a limiting factor for the clinical use of penetrating microelectrode recording arrays for the treatment of certain CNS disorders.
... Among them, strain and stress around the implantation site during electrode implantation are the main factors causing sustained brain tissue reactions, potentially exacerbating brain inflammation. Therefore, studying the process of electrode implantation into brain tissue is of positive significance for improving brain tissue injury and increasing the likelihood of successful implantation [13]. ...
Brain–computer interface (BCI) technology is currently a cutting-edge exploratory problem in the field of human–computer interaction. However, in experiments involving the implantation of electrodes into brain tissue, particularly high-speed or array implants, existing technologies find it challenging to observe the damage in real time. Considering the difficulties in obtaining biological brain tissue and the challenges associated with real-time observation of damage during the implantation process, we have prepared a transparent agarose gel that closely mimics the mechanical properties of biological brain tissue for use in electrode implantation experiments. Subsequently, we developed an experimental setup for synchronized observation of the electrode implantation process, utilizing the Digital Gradient Sensing (DGS) method. In the single electrode implantation experiments, with the increase in implantation speed, the implantation load increases progressively, and the tissue damage region around the electrode tip gradually diminishes. In the array electrode implantation experiments, compared to a single electrode, the degree of tissue indentation is more severe due to the coupling effect between adjacent electrodes. As the array spacing increases, the coupling effect gradually diminishes. The experimental results indicate that appropriately increasing the velocity and array spacing of the electrodes can enhance the likelihood of successful implantation. The research findings of this article provide valuable guidance for the damage assessment and selection of implantation parameters during the process of electrode implantation into real brain tissue.
... A long-term in vivo study indicated that failure of the insulation material is the most significant factor in the Frontiers in Neuroscience 08 frontiersin.org reduction of both signal quality and impedance of implanted electrodes (Barrese et al., 2013). Crosstalk is another limitation of high-density recording devices, which may occur between electrodes if the space is too close, resulting in low SNR, signal transmission error, or signal loss (McNamara et al., 2021;Qiang et al., 2021). ...
Flexible high-density microelectrode arrays (HDMEAs) are emerging as a key component in closed-loop brain–machine interfaces (BMIs), providing high-resolution functionality for recording, stimulation, or both. The flexibility of these arrays provides advantages over rigid ones, such as reduced mismatch between interface and tissue, resilience to micromotion, and sustained long-term performance. This review summarizes the recent developments and applications of flexible HDMEAs in closed-loop BMI systems. It delves into the various challenges encountered in the development of ideal flexible HDMEAs for closed-loop BMI systems and highlights the latest methodologies and breakthroughs to address these challenges. These insights could be instrumental in guiding the creation of future generations of flexible HDMEAs, specifically tailored for use in closed-loop BMIs. The review thoroughly explores both the current state and prospects of these advanced arrays, emphasizing their potential in enhancing BMI technology.
... Penetrating intracortical electrodes have the potential to offer finer spatial and temporal resolution neural data crucial for high degrees of freedom applications, surpassing the capabilities of surface or endovascular microelectrodes [19,20]. Despite their promising capabilities, the long-term efficacy of these neural electrodes is often compromised by tradeoffs in challenges related to their integration into host tissue [21][22][23][24][25][26][27][28], limited channel count [29], low recording site densities [29,30], and small recording radiuses [2,31]. These limitations have prompted researchers to explore innovative solutions to enhance the performance of these devices, paving the way for advancements in the development of high-density electrode arrays [32]. ...
... Penetrating intracortical electrodes have the potential to offer finer spatial and temporal resolution neural data crucial for high degrees of freedom applications, surpassing the capabilities of surface or endovascular microelectrodes [19,20]. Despite their promising capabilities, the long-term efficacy of these neural electrodes is often compromised by tradeoffs in challenges related to their integration into host tissue [21][22][23][24][25][26][27][28], limited channel count [29], low recording site densities [29,30], and small recording radiuses [2,31]. These limitations have prompted researchers to explore innovative solutions to enhance the performance of these devices, paving the way for advancements in the development of high-density electrode arrays [32]. ...
... These findings suggest that the BBB/vascular wall may exhibit greater structural stability compared to individual cells around the implant site with pneumatic insertion speeds. This aligns with previous observations that it takes several days for single-units to be detectable on pneumatically inserted Blackrock arrays in non-human primates [29]. Consequently, the study emphasizes that fast insertion speeds represent a compromise to minimize acute BBB and cell membrane rupture. ...
Objective: Over the past decade, neural electrodes have played a crucial role in bridging biological tissues with electronic and robotic devices. This study focuses on evaluating the optimal tip profile and insertion speed for effectively implanting Paradromics’ high-density Fine Microwire Arrays (FμA) prototypes into the primary visual cortex (V1) of mice and rats, addressing the challenges associated with the "bed-of-nails" effect and tissue dimpling. Approach: Tissue response was assessed by investigating the impact of electrodes on the blood-brain barrier (BBB) and cellular damage, with a specific emphasis on tailored insertion strategies to minimize tissue disruption during electrode implantation. Main Results: Electro-sharpened arrays demonstrated a marked reduction in cellular damage within 50 μm of the electrode tip compared to blunt and angled arrays. Histological analysis revealed that slow insertion speeds led to greater BBB compromise than fast and pneumatic methods. Successful single-unit recordings validated the efficacy of the optimized electro-sharpened arrays in capturing neural activity. Significance: These findings underscore the critical role of tailored insertion strategies in minimizing tissue damage during electrode implantation, highlighting the suitability of electro-sharpened arrays for long-term implant applications. This research contributes to a deeper understanding of the complexities associated with high-channel-count microelectrode array implantation, emphasizing the importance of meticulous assessment and optimization of key parameters for effective integration and minimal tissue disruption. By elucidating the interplay between insertion parameters and tissue response, our study lays a strong foundation for the development of advanced implantable devices with a reduction in reactive gliosis and improved performance in neural recording applications.
... Model shift, dataset shift, and nonstationarity are terms that have been used synonymously in the literature for this type of phenomenon [23][24][25][26][27][28][29][30] . Model drift can be attributed to various factors such as changes in action potential waveforms 18,31,32 , neural tuning profiles [33][34][35] , cognitive strategy or plasticity due to learning [36][37][38] , material degradation and tissue responses to the recording device 39,40 , and array micro-movements 41 . The type and magnitude of model drift results in various forms of performance degradation 19 , sometimes necessitating decoder recalibration to restore control. ...
Intracortical brain-computer interfaces (iBCIs) enable people with tetraplegia to gain intuitive cursor control from movement intentions. To translate to practical use, iBCIs should provide reliable performance for extended periods of time. However, performance begins to degrade as the relationship between kinematic intention and recorded neural activity shifts compared to when the decoder was initially trained. In addition to developing decoders to better handle long-term instability, identifying when to recalibrate will also optimize performance. We propose a method to measure instability in neural data without needing to label user intentions. Longitudinal data were analyzed from two BrainGate2 participants with tetraplegia as they used fixed decoders to control a computer cursor spanning 142 days and 28 days, respectively. We demonstrate a measure of instability that correlates with changes in closed-loop cursor performance solely based on the recorded neural activity (Pearson r = 0.93 and 0.72, respectively). This result suggests a strategy to infer online iBCI performance from neural data alone and to determine when recalibration should take place for practical long-term use.
... These properties minimize the initiation of the immune response (foreign body response), in the CNS represented as astrocytic barrier (Moshayedi et al., 2014;Sohal et al., 2016), and in PNS as fibrotic tissue around the nerve implanted (Christensen et al., 2014;González et al., 2018;Carnicer-Lombarte et al., 2021). The mechanical mismatch (neural interface-tissue) is a main contributor to inflammatory responses, which relies on the mechanical properties of the material implanted with higher stiffness than the soft neural tissue (i.e., Young's modulus) (Barrese et al., 2013;Moshayedi et al., 2014;Figure 11). The development of materials with low Young's modulus, closer to the values for neural tissue, has been demonstrated to minimize the inflammatory response (Nguyen et al., 2014;Potter et al., 2014;González et al., 2018). ...
... It has been used for decades to fabricate transistors, diodes, and integrated circuits, so it is well known in the industry for manufacturing silicon-based bioelectronic devices. However, silicon is a stiff and brittle material, far from the mechanical properties of the soft nervous tissue ( Figure 11A), which makes it not well suited for these purposes, where flexible and soft materials are preferred to prevent inflammation and foreign body response (Barrese et al., 2013;Kozai et al., 2015;Cody et al., 2018). ...
Bioelectronic Medicine stands as an emerging field that rapidly evolves and offers distinctive clinical benefits, alongside unique challenges. It consists of the modulation of the nervous system by precise delivery of electrical current for the treatment of clinical conditions, such as post-stroke movement recovery or drug-resistant disorders. The unquestionable clinical impact of Bioelectronic Medicine is underscored by the successful translation to humans in the last decades, and the long list of preclinical studies. Given the emergency of accelerating the progress in new neuromodulation treatments (i.e., drug-resistant hypertension, autoimmune and degenerative diseases), collaboration between multiple fields is imperative. This work intends to foster multidisciplinary work and bring together different fields to provide the fundamental basis underlying Bioelectronic Medicine. In this review we will go from the biophysics of the cell membrane, which we consider the inner core of neuromodulation, to patient care. We will discuss the recently discovered mechanism of neurotransmission switching and how it will impact neuromodulation design, and we will provide an update on neuronal and glial basis in health and disease. The advances in biomedical technology have facilitated the collection of large amounts of data, thereby introducing new challenges in data analysis. We will discuss the current approaches and challenges in high throughput data analysis, encompassing big data, networks, artificial intelligence, and internet of things. Emphasis will be placed on understanding the electrochemical properties of neural
... In addition, intracortical microelectrodes facilitate in brain mapping and neuroscience research. Unfortunately, intracortical microelectrodes typically show reduced recording and stimulation performance over time, leading to failure within weeks to months after implantation [9][10][11][12]. Reduced performance and eventual failure can result in reduced therapeutic efficacy of the brain-computer interface system. ...
... Mueller et al. 2 implantation of the device. Initial implantation causes vascular injury, compromising the blood-brain barrier and allowing macrophages, monocytes, and blood proteins to enter the brain [9,[13][14][15][16]. Additionally, resident immune cells of the brain, such as microglia and astrocytes, are activated and recruited to the implant site. ...
Intracortical microelectrodes (IMEs) can be used to restore motor and sensory function as a part of brain-computer interfaces in individuals with neuromusculoskeletal disorders. However, the neuroinflammatory response to IMEs can result in their premature failure, leading to reduced therapeutic efficacy. Mechanically-adaptive, resveratrol-eluting (MARE) neural probes target two mechanisms believed to contribute to the neuroinflammatory response by reducing the mechanical mismatch between the brain tissue and device, as well as locally delivering an antioxidant therapeutic. To create the mechanically-adaptive substrate, a dispersion, casting, and evaporation method is used, followed by a microfabrication process to integrate functional recording electrodes on the material. Resveratrol release experiments were completed to generate a resveratrol release profile and demonstrated that the MARE probes are capable of long-term controlled release. Additionally, our results showed that resveratrol can be degraded by laser-micromachining, an important consideration for future device fabrication.
... However, failure of such Si-based electrodes is frequently caused by connector and material problems associated with their stiffness. [13] Over the past thirty years, Utah arrays have been very successful in recording neural activity from deep brain regions. Recent Si technology advances featuring the fabrication of Utah-like arrays have allowed design flexibility and processing capabilities for the implementation of distinct electrode layouts, high-density electrodes, distinct needle geometries, and arbitrary needle heights, thereby allowing either a 2D (all shafts with the same height) or a 3D (e.g., Utah slant array) electrode spatial arrangement of penetrating MEAs. ...
Planar microelectrode arrays (MEAs) for – in vitro or in vivo – neuronal signal recordings lack the spatial resolution and sufficient signal‐to‐noise ratio (SNR) required for a detailed understanding of neural network function and synaptic plasticity. To overcome these limitations, a highly customizable three‐dimensional (3D) printing process is used in combination with thin film technology and a self‐aligned template‐assisted electrochemical deposition process to fabricate 3D‐printed‐based MEAs on stiff or flexible substrates. Devices with design flexibility and physical robustness are shown for recording neural activity in different in vitro and in vivo applications, achieving high‐aspect ratio 3D microelectrodes of up to 33:1. Here, MEAs successfully record neural activity in 3D neuronal cultures, retinal explants, and the cortex of living mice, thereby demonstrating the versatility of the 3D MEA while maintaining high‐quality neural recordings. Customizable 3D MEAs provide unique opportunities to study neural activity under regular or various pathological conditions, both in vitro and in vivo, and contribute to the development of drug screening and neuromodulation systems that can accurately monitor the activity of large neural networks over time.
... [35] Both mechanisms presuppose chemical and material interactions. [29,36,37] High chemical inertness and mechanical stability are set as prerequisites in the development of neural interfaces and material selection when entering the human body. Corrosive processes can be reinforced by inflammation mediators like reactive oxygen compounds and local decreases in pH, increasing the risk of dissolution and release of toxic compounds. ...
... Multiple groups show agreement on the consistent failure mechanisms over different systems of neural interfaces in sub-chronic as well as chronic time spans, however, no fundamental knowledge on the nature of the mechanisms themselves as well as the cause dependencies can be derived from the studies. [15,29,32,36,42] In the case of thin films, it is important to differentiate the associated physicochemical properties in the micro-range compared to their macroscopic scale. [35,43] This is explained by their increased surface-to-volume ratio as well as the different microstructures resulting from the fabrication process of film deposition. ...
The success of bioelectronics medicine with neural implants inevitably depends on the longevity of neural interfaces where a full understanding of the associated risks serves as the first step, to begin with. Until now, failure of neural electrodes is primarily explained by extreme electrochemical reactions, whereas no direct link between electrical stimulation and mechanical deformation of microelectrodes can be proved. The research provides new quantitative evidence of electrically induced mechanical vibrations in thin film neural interfaces. This study investigates the dynamic changes in intrinsic mechanical stress in clinically used neural electrodes under electrical stimulation. Via live imaging of the electrode plane, the deformation and progressive adhesion loss of the thin film during stimulation is for the first time approved. The results reveal nano‐oscillations in the interfaces under alternating current. This hints at a direct link between electrochemical charge transfer and mechanical stability. Considering neural interfaces as resonating actuators serves as a key to assessing the stability of neural interfaces and a valuable input to a longstanding question on the associated failure mechanisms of thin film microelectrodes. It is believed, that the outcome of this work may significantly contribute to improving the future design of thin film neural interfaces and better conditioning them for life‐long reliability.
