Stimulating Electrodes Research Articles

Molecular Insights into Transcranial Direct Current Stimulation Effects: Metabolomics and Transcriptomics Analyses.

Transcranial direct current stimulation (tDCS) is an evolving non-invasive neurostimulation technique. Despite multiple studies, its underlying molecular mechanisms are still unclear. Several previous human studies of the effect of tDCS suggest that it generates metabolic effects. The induction of metabolic effects by tDCS could provide an explanation for how it generates its long-term beneficial clinical outcome. Given these hints of tDCS metabolic effects, we aimed to delineate the metabolic pathways involved in its mode of action. To accomplish this, we utilized a broad analytical approach of co-analyzing metabolomics and transcriptomic data generated from anodal tDCS in rat models. Since no metabolomic dataset was available, we performed a tDCS experiment of bilateral anodal stimulation of 200 µA for 20 min and for 5 consecutive days, followed by harvesting the brain tissue below the stimulating electrode and generating a metabolomics dataset using LC-MS/MS. The analysis of the transcriptomic dataset was based on a publicly available dataset. Our analyses revealed that tDCS alters the metabolic profile of brain tissue, affecting bioenergetic-related pathways, such as glycolysis and mitochondrial functioning. In addition, we found changes in calcium-related signaling. We conclude that tDCS affects metabolism by modulating energy production-related processes. Given our findings concerning calcium-related signaling, we suggest that the immediate effects of tDCS on calcium dynamics drive modifications in distinct metabolic pathways. A thorough understanding of the underlying molecular mechanisms of tDCS has the potential to revolutionize its applicability, enabling the generation of personalized medicine in the field of neurostimulation and thus contributing to its optimization.

Effect of epiretinal electrical stimulation on the glial cells in a rabbit retinal eyecup model.

We examined how pulse train electrical stimulation of the inner surface of the rabbit retina effected the resident glial cells. We used a rabbit retinal eyecup preparation model, transparent stimulus electrodes, and optical coherence tomography (OCT). The endfeet of Müller glia processes line the inner limiting membrane (ILM). To examine how epiretinal electrode stimulation affected the Müller glia, we labeled them post stimulation using antibodies against soluble glutamine synthetase (GS). After 5 min 50 Hz pulse train stimulation 30 μm from the surface, the retina was fixed, immunostained for Müller glia, and examined using confocal microscopic reconstruction. Stimulus pulse charge densities between 133-749 μC/cm2/ph were examined. High charge density stimulation (442-749 μC/cm2/ph) caused significant losses in the GS immunofluorescence of the Müller glia endfeet under the electrode. This loss of immunofluorescence was correlated with stimuli causing ILM detachment when measured using OCT. Müller cells show potassium conductances at rest that are blocked by barium ions. Using 30 msec 20 μA stimulus current pulses across the eyecup, the change in transretinal resistance was examined by adding barium to the Ringer. Barium caused little change in the transretinal resistance, suggesting under low charge density stimulus pulse conditions, the Müller cell radial conductance pathway for these stimulus currents was small. To examine how epiretinal electrode stimulation affected the microglia, we used lectin staining 0-4 h post stimulation. After stimulation at high charge densities 749 μC/cm2/ph, the microglia under the electrode appeared rounded, while the local microglia outside the electrode responded to the stimulated retina by process orientation inwards in a ring by 30 min post stimulation. Our study of glial cells in a rabbit eyecup model using transparent electrode imaging suggests that epiretinal electrical stimulation at high pulse charge densities, can injure the Müller and microglia cells lining the inner retinal surface in addition to ganglion cells.

Targeting Transcutaneous Spinal Cord Stimulation Using a Supervised Machine Learning Approach Based on Mechanomyography.

Transcutaneous spinal cord stimulation (tSCS) provides a promising therapy option for individuals with injured spinal cords and multiple sclerosis patients with spasticity and gait deficits. Before the therapy, the examiner determines a suitable electrode position and stimulation current for a controlled application. For that, amplitude characteristics of posterior root muscle (PRM) responses in the electromyography (EMG) of the legs to double pulses are examined. This laborious procedure holds potential for simplification due to time-consuming skin preparation, sensor placement, and required expert knowledge. Here, we investigate mechanomyography (MMG) that employs accelerometers instead of EMGs to assess muscle activity. A supervised machine-learning classification approach was implemented to classify the acceleration data into no activity and muscular/reflex responses, considering the EMG responses as ground truth. The acceleration-based calibration procedure achieved a mean accuracy of up to 87% relative to the classical EMG approach as ground truth on a combined cohort of 11 healthy subjects and 11 patients. Based on this classification, the identified current amplitude for the tSCS therapy was in 85%, comparable to the EMG-based ground truth. In healthy subjects, where both therapy current and position have been identified, 91% of the outcome matched well with the EMG approach. We conclude that MMG has the potential to make the tuning of tSCS feasible in clinical practice and even in home use.

Liquid-metal-based three-dimensional microelectrode arrays integrated with implantable ultrathin retinal prosthesis for vision restoration

Electronic retinal prostheses for stimulating retinal neurons are promising for vision restoration. However, the rigid electrodes of conventional retinal implants can inflict damage on the soft retina tissue. They also have limited selectivity due to their poor proximity to target cells in the degenerative retina. Here we present a soft artificial retina (thickness, 10 μm) where flexible ultrathin photosensitive transistors are integrated with three-dimensional stimulation electrodes of eutectic gallium–indium alloy. Platinum nanoclusters locally coated only on the tip of these three-dimensional liquid-metal electrodes show advantages in reducing the impedance of the stimulation electrodes. These microelectrodes can enhance the proximity to the target retinal ganglion cells and provide effective charge injections (72.84 mC cm−2) to elicit neural responses in the retina. Their low Young’s modulus (234 kPa), owing to their liquid form, can minimize damage to the retina. Furthermore, we used an unsupervised machine learning approach to effectively identify the evoked spikes to grade neural activities within the retinal ganglion cells. Results from in vivo experiments on a retinal degeneration mouse model reveal that the spatiotemporal distribution of neural responses on their retina can be mapped under selective localized illumination areas of light, suggesting the restoration of their vision.

Influence of the electrolyte concentration and amount on the performance of textile electrodes in electrostimulation: A systematic study

BackgroundTextile-based stimulation electrodes are a fast-growing research area. With their advantages including flexibility, reusability and the possibility for integration into garments, textile electrodes open up new possibilities that are not yet feasible today, e.g. various self-administrated treatments and rehabilitation based on neuromuscular electrical stimulation (NMES) or transcutaneous electrical nerve stimulation (TENS). So far, most research has shown that textile-based stimulation electrodes perform more reliable when wetted with an electrolyte. However, there is no systematic investigation about which type and amount of electrolyte to use. MethodsIn this study, double-layered textile electrodes have been produced by machine knitting with a size of 3 × 3 cm2. The electrodes were wetted stepwise with a liquid amount from 5 µL up to 320 µL; four levels of sodium chloride (NaCl) concentrations, i.e. 0.9%, 1.5%, 5% and 35%, plus pure deionized water as a reference liquid were chosen. The study analyzed the behavior of the skin-electrode impedance when changing the moisture content and NaCl concentration. In addition, equivalent circuits were modelled for deeper insights into the mechanisms causing an impedance change. ResultsResults showed that the impedance was greatly influenced by the liquid amount with amounts of 5 µL already significantly reducing the impedance compared to dry electrodes, caused by a substantial reduction in resistance. The reactance, on the other hand, was only partly influenced by the liquid amount showing a reduction upon higher liquid amounts only within a range of 5 – 40 µL. Further, a significant influence on the impedance by the presence of ions was found where the skin-electrode systems wetted with NaCl solution were showing generally lower impedances than systems wetted with deionized water. However, within this, no remarkable influence of the NaCl concentration could be observed. As the impedance was found to be very sensitive to the moisture content in the system, it is recommended to introduce standardizations for impedance testing of wet textile electrodes with precisely controlled electrolyte volumes and liquid migration properties to make independent studies of textile electrodes more comparable.

System of Implantable Electrodes for Neural Signal Acquisition and Stimulation for Wirelessly Connected Forearm Prosthesis.

There is great interest in the development of prosthetic limbs capable of complex activities that are wirelessly connected to the patient's neural system. Although some progress has been achieved in this area, one of the main problems encountered is the selective acquisition of nerve impulses and the closing of the automation loop through the selective stimulation of the sensitive branches of the patient. Large-scale research and development have achieved so-called "cuff electrodes"; however, they present a big disadvantage: they are not selective. In this article, we present the progress made in the development of an implantable system of plug neural microelectrodes that relate to the biological nerve tissue and can be used for the selective acquisition of neuronal signals and for the stimulation of specific nerve fascicles. The developed plug electrodes are also advantageous due to their small thickness, as they do not trigger nerve inflammation. In addition, the results of the conducted tests on a sous scrofa subject are presented.

A transcutaneous acupoint electrical simulation glove for relieving the mental fatigue of crane drivers in real building environment

In the field of construction, the lifting environment of precast parts is more complex, which leads to the driver’s fatigue. When the tower crane driver appears driving fatigue, it will appear slow operation response, hoisting precast parts appear abnormal swing, which will endanger the safety of on-site operators. Therefore, this study developed a kind of transcutaneous acupoint electrical stimulation gloves. When the crane driver wears this kind of glove, the good contraction of the glove can make the stimulation electrode closely fit with the three points, so as to perform electrical stimulation on the Neìguān point (内关PC6), Láogóng point (劳宫PC8) and Hégŭ point (合谷L14) of the palm to relieve the driver’s driving fatigue. In this study, non-periodic transcutaneous acupoint electrical stimulation (NPTAES) was used to stimulate human acupuncture points. This is different from the traditional periodic transcutaneous acupoint electrical stimulation (PTAES) method for relieving mental fatigue. In addition, this study used hilbert marginal spectral entropy (HMSE) to calculate the heart rate variability (HRV) characteristics of the subjects, so as to detect and analyze the driving fatigue of the drivers. At the same time, the drivers’ blinking frequency and electroencephalogram (EEG) characteristics were analyzed comprehensively. The results show that: The NPTAES method used in this study is superior to the PTAES method in alleviating driving fatigue and greatly improves the efficiency of tower crane drivers. Compared to other methods, the HMSE method proposed in this study, when analyzing signals, stronger ability to characterize signal characteristics.

Electrically evoked late latency response using single electrode stimulation and its relation to speech perception among paediatric cochlear implant users.

Aided auditory late latency response (LLR) serves as an objective tool for evaluating auditory cortical maturation following cochlear implantation in children. While aided LLR is commonly measured using sound-field acoustic stimulation, recording electrically evoked LLR (eLLR) offer distinct advantages, such as improved stimulus control and the capability for single electrode stimulation. Hence, the study aimed to compare eLLR responses with single electrode stimulation in the apical, middle, and basal regions and to evaluate their relationship with speech perception in paediatric cochlear implant (CI) recipients. eLLR responses with single electrode stimulation were measured in 27 paediatric unilateral CI users with an active recording electrode placed at Cz. The stimuli consisted of 36 msec biphasic pulse trains presented across three electrode sites (apical-E20, middle-E11, and basal-E03). eLLR responses were compared across these electrode sites, and the relationship between speech recognition scores in quiet and age at implantation with eLLR components was evaluated. eLLR responses were detected in 77 out of 81 tested electrodes of all participants combined (27 for apical, 26 for middle, and 24 for basal stimulation). There were no significant differences in P1, N1 latencies and P1 amplitude across electrode site. However, significantly larger N1 and P1-N1 amplitudes were observed for apical stimulations compared to basal stimulations. No differences in N1 amplitude were found between middle and apical stimulations, and the P1-N1 amplitude was significantly larger for middle compared to basal electrode stimulation, with no difference between the apical and middle electrodes stimulation. A moderate positive correlation was present between speech recognition scores in quiet and both N1, P1-N1 amplitudes for apical stimulation. Age at implantation was negatively correlated with N1 amplitude for the apical and P1-N1 amplitude for basal stimulation. eLLR responses could be elicited in majority of paediatric CI users across electrode sites. Variations in eLLR responses across electrode sites suggest disparities in auditory cortical maturation. The findings underscore the significance of the N1 biomarker in evaluating higher-order auditory cortical development. Therefore, utilizing eLLR with single electrode stimulation may serve as a valuable tool for assessing post-cochlear implantation maturational changes in paediatric populations.

Electric field temporal interference stimulation of neurons in vitro.

Electrical stimulation (ES) techniques, such as deep brain and transcranial electrical stimulation, have shown promise in alleviating the symptoms of depression and other neurological disorders in vivo. A new noninvasive ES method called temporal interference stimulation (TIS), possesses great potential as it can be used to steer the stimulation and possibly selectively modulate different brain regions. To study TIS in a controlled environment, we successfully established an in vitro 'TIS on a chip' setup using rat cortical neurons on microelectrode arrays (MEAs) in combination with a current stimulator. We validated the developed TIS system and demonstrated the spatial steerability of the stimulation by direct electric field measurements in the chip setup. We stimulated cultures of rat cortical neurons at 28 days in vitro (DIV) by two-channel stimulation delivering 1) TIS at 653 Hz and 643 Hz, resulting in a 10 Hz frequency envelope, 2) low-frequency stimulation (LFS) at 10 Hz and 3) high-frequency stimulation (HFS) at 653 Hz. Unstimulated cultures were used as control/sham. We observed the differences in the electric field strengths during TIS, HFS, and LFS. Moreover, HFS and LFS had the smallest effects on neuronal activity. Instead, TIS elicited neuronal electrophysiological responses, especially 24 hours after stimulation. Our 'TIS on a chip' approach eludicates the applicability of TIS as a method to modulate neuronal electrophysiological activity. The TIS on a chip approach provides spatially steerable stimuli while mitigating the effects of high stimulus fields near the stimulation electrodes. Thus, the approach opens new avenues for stimulation on a chip applications, allowing the study of neuronal responses to gain insights into the potential clinical applications of TIS in treating various brain disorders.

Cluster Neuronal Firing Induced by Uniform Pulses of High-Frequency Stimulation on Axons in Rat Hippocampus.

High-frequency stimulation (HFS) of electrical pulse sequences has been used in various neuromodulation techniques to treat certain disorders. Here, we test the hypothesis that HFS sequences with purely periodic pulses could directly generate non-uniform firing in directly stimulated neurons. In vivo experiments were conducted in the rat hippocampal CA1 region. A stimulation electrode was placed on the alveus fibers, and a recording electrode array was inserted into the CA1 region upstream of the stimulation site. Antidromic-HFS (A-HFS) of 100 Hz pulses was applied to the alveus to antidromically activate the soma of pyramidal neurons around the recording site. By minimizing the interferences of population spikes, the evoked unit spikes of individual pyramidal neurons were obtained during A-HFS. Additionally, a computational model of pyramidal neuron was used to simulate the neuronal responses to A-HFS, revealing possible mechanisms underlying the different firing patterns. Of the total 54 pyramidal neurons recorded during 2-min 100 Hz A-HFS, 38 (70%) neurons fired in a cluster pattern with alternating periods of intensive spikes and silence. The remaining 16 (30%) neurons fired in a non-cluster pattern with regular spikes. Modeling simulations showed that under the situation of HFS-induced intermittent block, conduction failure and generation failure of action potentials along the axons resulted in the cluster and non-cluster firing. Sustained axonal A-HFS with periodic pulses can induce non-uniform firing in directly stimulated neurons. This finding provides new evidence for the nonlinear dynamics of neuronal firing, even under uniform stimulation.

Therapeutic effects of a novel electrode for transcranial direct current stimulation in ischemic stroke mice.

Rationale: Non-invasive transcranial direct current stimulation (tDCS), a promising stimulation tool to modulate a wide range of brain disorders, has major limitations, such as poor cortical stimulation intensity and focality. We designed a novel electrode for tDCS by conjugating a needle to a conventional ring-based high-definition (HD) electrode to enhance cortical stimulation efficacy. Method: HD-tDCS (43 µA/mm2, charge density 51.6 kC/m2, 20 min) was administered to male C57BL/6J mice subjected to early-stage ischemic stroke. Behavioral tests were employed to determine the therapeutic effects, and the underlying mechanisms of HD-tDCS were determined by performing RNA sequencing and other biomedical analyses. Results: The new HD-tDCS application, showing a higher electric potential and spatial focality based on computational modeling, demonstrated better therapeutic effects than conventional HD-tDCS in alleviating motor and cognitive deficits, with a decrease in infarct volume and inflammatory response. We assessed different electrode configurations in the new HD electrode; the configurations variously showed potent therapeutic effects, ameliorating neuronal death in the peri-infarct region via N-methyl-D-aspartate-dependent sterol regulatory element-binding protein 1 signaling and related inflammatory factors, further alleviating motor and cognitive deficits in stroke. Conclusion: This new HD-tDCS application showed better therapeutic effects than those with conventional HD-tDCS in early-stage stroke via the amelioration of neuronal death in the penumbra. It may be applied in the early stages of stroke to alleviate neurological impairment.

Nerve Preparation and Recordings for Pharmacological Tests of Sensory and Nociceptive Fiber Conduction Ex Vivo.

Measuring signal propagation through nerves is a classical electrophysiological technique established decades ago to evaluate sensory and motor functions in the nervous system. The whole-nerve preparation provides a valuable model to investigate nerve function ex vivo; however, it requires specific knowledge to ensure successful and stable measurements. Although the methodology for sciatic nerve recordings has long existed, a method for reliable and long-lasting recordings from myelinated and non-myelinated (nociceptive) fibers still needs to be adapted for pharmacological testing. This protocol takes benefits from epineurium sheath removal for pharmacological tests and provides a detailed description of how to make accurate nerve preparations, from the dissection and handling of nerves to epineurium cleaning, fabrication of adaptable suction electrodes for appropriate fiber stimulation and recordings, setting of electrophysiological protocols for compound action potential (CAP) recordings to distinguish between myelinated and non-myelinated (nociceptive) fibers, and finally to the analysis of the datasets of CAP components. We also demonstrate the feasibility of CAP recordings from individual branches in epineurium-free nerve preparations and provide clues to help retain nerve viability and maintain stable recordings over time. Although a sciatic nerve preparation was used here, the methodology can be applied to other nerve-type preparations. Key features • Detailed and simplified protocol for peripheral nerve preparation for recording sensory inputs ex vivo. • Recordings from myelinated and non-myelinated (nociceptive) fibers can be performed hours after nerve preparation. • The protocol involves the epineurium removal to facilitate drug permeability into nerve tissue for pharmacological tests. • The protocol allows physiological and pathological studies (pain/chronic pain conditions).

Single-center experience of utilization and clinical efficacy of segmented leads for subthalamic deep brain stimulation in Parkinson’s disease

BackgroundSegmented electrodes for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s disease (PD) enable directional current steering leading to expanded programming options. ObjectiveThis retrospective study covering a longitudinal period of up to 7 years compares the efficacy of segmented and non-segmented leads in motor symptom alleviation and reduction of dopaminergic medication in PD patients treated in a specialized center and assesses the long-term use of directional steering in clinical routine. MethodsDemographic data and clinical scores before surgery and at 12-month follow-up (12MFU) as well as stimulation parameters at 12MFU and last follow-up (LFU) were assessed in all patients implanted with segmented leads between 01/2016 and 12/2019 and non-segmented leads in a corresponding time-period. Patients were classified as very good (>60 %), good (30–60 %) and poor (<30 %) responders according to DBS-induced motor improvement. ResultsClinical data at 12MFU was available for 61/96 patients with segmented (SEG) and 42/53 with non-segmented leads (N-SEG). Mean DBS-induced motor improvement and reduction of medication at 12MFU did not differ significantly between SEG and N-SEG groups or in a subgroup analysis of steering modes. There was a lower proportion of poor responders in the SEG compared with the N-SEG group (23% vs. 31%), though not statistically significant. At LFU, the percentage of patients set at directional steering increased from 54% to 70%. ConclusionEfficacy in reduction of motor symptoms and medication does not differ between electrode types for STN-DBS at 12 months follow-up. The use of directional steering increases over time and may account for a lower proportion of poor responders.

In vivo photopharmacological inhibition of hippocampal activity via multimodal probes - perspective and opening steps on experimental and computational challenges.

Neurological conditions such as epilepsy can have a significant impact on people's lives. Here, we discuss a new perspective for the study/treatment of these conditions using photopharmacology. A multimodal, intracranial implant that incorporates fluidic channels for localised drug delivery, electrodes for recording and stimulation, and a light source for photoswitching is used for in vivo administration and deactivation of a photoresponsive AMPA antagonist. We review current advancements in the relevant disciplines and show experimentally that the inhibition of seizure-like events induced in the hippocampus by electrical stimulation can be altered upon switching the drug with light. We discuss the interconnection of the drug's photopharmacological properties with the design of the device by modelling light penetration into the rat brain with Monte Carlo simulations. This work delivers a new perspective, including initial experimental and computational efforts on in vivo photopharmacology to understand and eventually treat neurological conditions.

Functional Electrochemistry: On-Nerve Assessment of Electrode Materials for Electrochemistry and Functional Neurostimulation.

Emerging therapies in bioelectronic medicine highlight the need for deeper understanding of electrode material performance in the context of tissue stimulation. Electrochemical properties are characterized on the benchtop, facilitating standardization across experiments. On-nerve electrochemistry differs from benchtop characterization and the relationship between electrochemical performance and nerve activation thresholds are not commonly established. This relationship is important in understanding differences between electrical stimulation requirements and electrode performance. We report functional electrochemistry as a follow-up to benchtop testing, describing a novel experimental approach for evaluating on-nerve electrochemical performance in the context of nerve activation. An ex-vivo rat sciatic nerve preparation was developed to quantify activation thresholds of fiber subtypes and electrode material charge injection limits for platinum iridium, iridium oxide, titanium nitride and PEDOT. Finally, we address experimental complexities arising in these studies, and demonstrate statistical solutions that support rigorous material performance comparisons for decision making in neural interface development.

Parasitic Capacitance in High-Density Neural Electrode Arrays: Sources and Evaluation Methods.

This study aims to identify sources of parasitic capacitance in high-density neural electrode arrays and to provide an approach for evaluating their associated capacitance values. We also represent the effect of parasitic capacitance on the electrochemical properties of electrodes. Electrochemical impedance spectroscopy (EIS) and voltage transient (VT) measurements were employed to assess the parasitic capacitance of a 16-channel ultramicro-sized electrode array (UMEA) (8×25 μm2 electrode sites). The effect of parasitic capacitance on cyclic voltammetry (CV), EIS, and VT measurements of 20-μm diameter electrodes was assessed by comparing two different array designs: narrow and wide trace arrays. The capacitive leakage currents and charge during CV measurements were not significant, however, during current pulsing 34% underestimation of the maximum charge injection capacity corresponded to capacitive leakage. Capacitive leakage during EIS resulted in an underestimation of the electrode impedance at frequencies >1.5 kHz. The electrode design and insulation thickness can play a significant role in determining the amount of capacitive leakage during current pulsing and EIS at higher frequencies. Determining the sources and levels of capacitive leakage current in high-density neural electrode arrays, enables us to correct the measured value for the leakage current and thus estimate the electrode impedance and stimulation thresholds more accurately. This study highlights the importance of electrode design in developing high-density arrays with minimum capacitive leakage.

Characterization of Induced Current Density During Transcorneal Electrical Stimulation to Promote Neuroprotection in the Degenerating Retina.

Transcorneal electrical stimulation (TES) is a promising approach to delay retinal degeneration by inducing extracellular electric field-driven neuroprotective effects within photoreceptors. Although achieving precise electric field control is feasible in vitro, characterizing these fields becomes intricate and largely unexplored in vivo due to uneven distribution in the heterogeneous body. In this paper, we investigate and characterize electric fields within the retina during TES to assess the potential for therapeutic approaches Methods: We developed a computational model of a rat's head, enabling us to generate predictive simulations of the voltage and current density induced in the retina. Subsequently, an in vivo experimental setup involving Royal College of Surgeon (RCS) rats was implemented to measure the voltage across the retina using identical electrode configurations as employed in the simulations. A stimulation amplitude of 0.2-0.3 mA may be necessary during TES in rats to induce a current density of at least 20 A/m2 in the retina, which is the lower limit for triggering neuroprotective effects according to culture studies on neural cells. Measurement taken from cadaveric pigs' eyes revealed that a stimulation amplitude of 1 mA is necessary for achieving the same current density. The computational modeling approach presented in this study was validated with experimental data and can be leveraged for predictive simulations to optimize the electrode design and stimulation parameters of TES. Once validated, the flexibility and low research cost of computational models are valuable in optimization studies where testing on live subjects is not feasible.

Effect of electrode attachment location for transcutaneous electrical nerve stimulation for pain relief in lumbar vertebral body fractures.

[Purpose] This study aimed to investigate the effect of the location of electrode attachment in transcutaneous electrical nerve stimulation on pain relief in patients with lumbar vertebral body fractures. [Participants and Methods] This study included 59 patients with lumbar vertebral body fractures, who were randomly assigned to receive transcutaneous electrical nerve stimulation to the lumbar region, lower limbs, or upper limbs, or no treatment, over a 4-week period. Pain, activities of daily living, and pain catastrophizing were assessed. [Results] Compared with the control group, transcutaneous electrical nerve stimulation to the lumbar region or lower limbs significantly reduced pain levels in the first 2 weeks. Although, activities of daily living and pain catastrophizing improved over time, no significant differences were observed between the groups. [Conclusion] Transcutaneous electrical nerve stimulation provides pain relief to patients during the early stages of lumbar vertebral body fractures. However, it had no effect on the activities of daily living, pain catastrophizing, or long-term pain-relief. For lumbar vertebral body fracture pain relief, transcutaneous electrical nerve stimulation electrodes should be attached to the lumbar region or lower limbs.

Directionally non-rotating electric field therapy delivered through implanted electrodes as a glioblastoma treatment platform: A proof-of-principle study.

While directionally rotating tumor-treating fields (TTF) therapy has garnered considerable clinical interest in recent years, there has been comparatively less focus on directionally non-rotating electric field therapy (dnEFT). We explored dnEFT generated through customized electrodes as a glioblastoma therapy in in vitro and in vivo preclinical models. The effects of dnEFT on tumor apoptosis and microglia/macrophages in the tumor microenvironment were tested using flow-cytometric and qPCR assays. In vitro, dnEFT generated using a clinical-grade spinal cord stimulator showed antineoplastic activity against independent glioblastoma cell lines. In support of the results obtained using the clinical-grade electrode, dnEFT delivered through a customized, 2-electrode array induced glioblastoma apoptosis. To characterize this effect in vivo, a custom-designed 4-electrode array was fabricated such that tumor cells can be implanted into murine cerebrum through a center channel equidistant from the electrodes. After implantation with this array and luciferase-expressing murine GL261 glioblastoma cells, mice were randomized to dnEFT or placebo. Relative to placebo-treated mice, dnEFT reduced tumor growth (measured by bioluminescence) and prolonged survival (median survival gain of 6.5 days). Analysis of brain sections following dnEFT showed a notable increase in the accumulation of peritumoral macrophage/microglia with increased expression of M1 genes (IFNγ, TNFα, and IL-6) and decreased expression of M2 genes (CD206, Arg, and IL-10) relative to placebo-treated tumors. Our results suggest therapeutic potential in glioblastoma for dnEFT delivered through implanted electrodes, supporting the development of a proof-of-principle clinical trial using commercially available deep brain stimulator electrodes.

A workflow for predicting radiofrequency-induced heating around bilateral deep brain stimulation electrodes in MRI.

Heating around deep brain stimulation (DBS) in magnetic resonance imaging (MRI) occurs when the time-varying electromagnetic (EM) fields induce currents in the electrodes which can generate heat and potentially cause tissue damage. Predicting the heating around the electrode contacts is important to ensure the safety of patients with DBS implants undergoing an MRI scan. We previously proposed a workflow to predict heating around DBS contacts and introduced a parameter, equivalent transimpedance, that is independent of electrode trajectories, termination, and radiofrequency (RF) excitations. The workflow performance was validated in a unilateral DBS system. To predict RF heating around the contacts of bilateral (DBS) electrodes during an MRI scan in an anthropomorphic head phantom. Bilateral electrodes were fixed in a skull phantom filled with hydroxyethyl cellulose (HEC) gel. The electrode shafts were suspended extracranially, in a head and torso phantom filled with the same gel material. The current induced on the electrode shaft was experimentally measured using an MR-based technique 3cm above the tip. A transimpedance value determined in a previous offline calibration was used to scale the shaft current and calculate the contact voltage. The voltage was assigned as a boundary condition on the electrical contacts of the electrode in a quasi-static (EM) simulation. The resulting specific absorption rate (SAR) distribution became the input for a transient thermal simulation and was used to predict the heating around the contacts. RF heating experiments were performed for eight different lead trajectories using circularly polarized (CP) excitation and two linear excitations for one trajectory. The measured temperatures for all experiments were compared with the simulated temperatures and the root-mean-squared errors (RMSE) were calculated. The RF heating around the contacts of both bilateral electrodes was predicted with ≤ 0.29°C of RMSE for 20 heating scenarios. The workflow successfully predicted the heating for different bilateral DBS trajectories and excitation patterns in an anthropomorphic head phantom.