The brain is a massive neuronal network, organized into anatomically distributed sub-circuits, with functionally relevant activity occurring at timescales ranging from milliseconds to years. Current ...methods to monitor neural activity, however, lack the necessary conjunction of anatomical spatial coverage, temporal resolution, and long-term stability to measure this distributed activity. Here we introduce a large-scale, multi-site, extracellular recording platform that integrates polymer electrodes with a modular stacking headstage design supporting up to 1,024 recording channels in freely behaving rats. This system can support months-long recordings from hundreds of well-isolated units across multiple brain regions. Moreover, these recordings are stable enough to track large numbers of single units for over a week. This platform enables large-scale electrophysiological interrogation of the fast dynamics and long-timescale evolution of anatomically distributed circuits, and thereby provides a new tool for understanding brain activity.
•Modular polymer electrode-based system capable of recording up to 1,024 channels•Recording from 375 single units across multiple regions in freely behaving rats•Single-unit recording longevity for 160 or more days post-implantation•System capable of tracking populations of single units continuously for over a week
Chung et al. present a large-scale, multi-site, polymer electrode-based recording platform. The modular system is capable of data collection from up to 1,024 channels in freely behaving rats, enabling long-term studies of distributed networks.
Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression and is being investigated in heart failure, headache, gastric motility disorders and asthma. The first VNS device ...required surgical implantation of electrodes and a stimulator. Adverse events (AEs) are generally associated with implantation or continuous on−off stimulation. Infection is the most serious implantation‐associated AE. Bradycardia and asystole have also been described during implantation, as has vocal cord paresis, which can last up to 6 months and depends on surgical skill and experience. The most frequent stimulation‐associated AEs include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis and pain, which may require a decrease in stimulation strength or intermittent or permanent device deactivation. Newer non‐invasive VNS delivery systems do not require surgery and permit patient‐administered stimulation on demand. These non‐invasive VNS systems improve the safety and tolerability of VNS, making it more accessible and facilitating further investigations across a wider range of uses.
Recent initiatives in bioelectronic modulation of the nervous system by the NIH (SPARC), DARPA (ElectRx, SUBNETS) and the GlaxoSmithKline Bioelectronic Medicines effort are ushering in a new era of ...therapeutic electrical stimulation. These novel therapies are prompting a re-evaluation of established electrical thresholds for stimulation-induced tissue damage.
In this review, we explore what is known and unknown in published literature regarding tissue damage from electrical stimulation.
For macroelectrodes, the potential for tissue damage is often assessed by comparing the intensity of stimulation, characterized by the charge density and charge per phase of a stimulus pulse, with a damage threshold identified through histological evidence from in vivo experiments as described by the Shannon equation. While the Shannon equation has proved useful in assessing the likely occurrence of tissue damage, the analysis is limited by the experimental parameters of the original studies. Tissue damage is influenced by factors not explicitly incorporated into the Shannon equation, including pulse frequency, duty cycle, current density, and electrode size. Microelectrodes in particular do not follow the charge per phase and charge density co-dependence reflected in the Shannon equation. The relevance of these factors to tissue damage is framed in the context of available reports from modeling and in vivo studies.
It is apparent that emerging applications, especially with microelectrodes, will require clinical charge densities that exceed traditional damage thresholds. Experimental data show that stimulation at higher charge densities can be achieved without causing tissue damage, suggesting that safety parameters for microelectrodes might be distinct from those defined for macroelectrodes. However, these increased charge densities may need to be justified by bench, non-clinical or clinical testing to provide evidence of device safety.
To sustainably power electronics by harvesting mechanical energy using nanogenerators, energy storage is essential to supply a regulated and stable electric output, which is traditionally realized by ...a direct connection between the two components through a rectifier. However, this may lead to low energy-storage efficiency. Here, we rationally design a charging cycle to maximize energy-storage efficiency by modulating the charge flow in the system, which is demonstrated on a triboelectric nanogenerator by adding a motion-triggered switch. Both theoretical and experimental comparisons show that the designed charging cycle can enhance the charging rate, improve the maximum energy-storage efficiency by up to 50% and promote the saturation voltage by at least a factor of two. This represents a progress to effectively store the energy harvested by nanogenerators with the aim to utilize ambient mechanical energy to drive portable/wearable/implantable electronics.
Spinal cord stimulation is an evidence-based treatment for a number of chronic pain conditions. While this therapy offers improvement in pain and function it is not without potential complications. ...These complications include device failure, migration, loss of therapeutic paresthesia, and infection. This article looked to establish a modern infection rate for spinal cord stimulators, assess the impact of known risk factors for surgical site infections and to determine the impact of certain preventative measures on the rate of infection.
After institutional review board approval, a multisite, retrospective review was conducted on 2737 unique implants or revisions of SCS systems. Patient demographics, risk factors including diabetes, tobacco use, obesity, revision surgery, trial length, implant location, implant type, surgeon background, prophylactic antibiotic use, utilization of a occlusive dressing, and post-operative antibiotic use were recorded and analyzed.
The overall infection rate was 2.45% (n = 67). Diabetes, tobacco use, and obesity did not independently increase the rate of infection. Revision surgeries had a trend toward higher infection rate; however, this did not meet statistical significance. There was no difference in the rate of infection between implants performed by physicians of different base specialties, cylinder leads vs. paddle leads, or between different prophylactic antibiotics. Implants performed at academic centers had a higher rate of infection when compared to implants performed in nonacademic settings. When patients received an occlusive dressing or post-operative antibiotics they had a lower rate of infection.
The infection rate (2.45%) reported in this study is lower than the previously reported rates (3-6%) and are on par with other surgical specialties. This study did not show an increased rate of infection for patients that used tobacco, had diabetes or were obese. It's possible that given the low overall infection rate a larger study is needed to establish the true impact of these factors on infection. In addition, this study did not address the impact of poorly controlled diabetes mellitus (elevated hemoglobin A1c) vs. well-controlled diabetes. It can be concluded from this study that utilizing an occlusive dressing over the incision in the post-operative period decreases the rate of infection and should become the standard of care. This study also demonstrated the positive impact of post-operative antibiotics in decreasing the rate of infection. Studies in other surgical specialties have not shown this impact which would suggest that further research is needed.
A totally soft organic subdural electrode has been developed by embedding an array of poly(3,4-ethylenedioxythiophene)-modified carbon fabric (PEDOT-CF) into the polyvinyl alcohol (PVA) hydrogel ...substrate. The mesh structure of the stretchable PEDOT-CF allowed stable structural integration with the PVA substrate. The electrode performance for monitoring electrocorticography (ECoG) was evaluated in saline solution, on ex vivo brains, and in vivo animal experiments using rats and porcines. It was demonstrated that the large double-layer capacitance of the PEDOT-CF brings low impedance at the frequency of brain wave including epileptic seizures, and PVA hydrogel substrate minimized the contact impedance on the brain. The most important unique feature of the hydrogel-based ECoG electrode was its shape conformability to enable tight adhesion even to curved, grooved surface of brains by just being placed. In addition, since the hydrogel-based electrode is totally organic, the simultaneous ECoG-fMRI measurements could be conducted without image artifacts, avoiding problems induced by conventional metallic electrodes.
Despite its long-reported successful record, with almost 60 years of clinical use, the technical complexity regarding the placement of stereoelectroencephalography (SEEG) depth electrodes may have ...contributed to the limited widespread application of the technique in centers outside Europe. The authors report on a simplified and novel SEEG surgical technique in the extraoperative mapping of refractory focal epilepsy.
The proposed technique was applied in patients with medically refractory focal epilepsy. Data regarding general demographic information, method of electrode implantation, time of implantation, number of implanted electrodes, seizure outcome after SEEG-guided resections, and complications were prospectively collected.
From March 2009 to April 2012, 122 patients underwent SEEG depth electrode implantation at the Cleveland Clinic Epilepsy Center in which the authors' technique was used. There were 65 male and 57 female patients whose mean age was 33 years (range 5-68 years). The group included 21 pediatric patients (younger than 18 years). Planning and implantations were performed in a single stage. The time for planning was, on average, 33 minutes (range 20-47 minutes), and the time for implantation was, on average, 107 minutes (range 47-150 minutes). Complications related to the SEEG technique were observed in 3 patients. The calculated risk of complications per electrode was 0.18%. The seizure-free rate after SEEG-guided resections was 62% in a mean follow-up period of 12 months.
The authors report on a safe, simplified, and less time-consuming method of SEEG depth electrode implantation, using standard and widely available surgical tools, making the technique a reasonable option for extraoperative monitoring of patients with medically intractable epilepsy in centers lacking the Talairach stereotactic armamentarium.
Neural recording electrode technologies have contributed considerably to neuroscience by enabling the extracellular detection of low-frequency local field potential oscillations and high-frequency ...action potentials of single units. Nevertheless, several long-standing limitations exist, including low multiplexity, deleterious chronic immune responses and long-term recording instability. Driven by initiatives encouraging the generation of novel neurotechnologies and the maturation of technologies to fabricate high-density electronics, novel electrode technologies are emerging. Here, we provide an overview of recently developed neural recording electrode technologies with high spatial integration, long-term stability and multiple functionalities. We describe how these emergent neurotechnologies can approach the ultimate goal of illuminating chronic brain activity with minimal disruption of the neural environment, thereby providing unprecedented opportunities for neuroscience research in the future.
Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the ...Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice.
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