Electrical stimulation enhances sciatic nerve regeneration using a silk-based conductive scaffold beyond traditional nerve guide conduits.

Despite recent advancements in peripheral nerve regeneration, the creation of nerve conduits with chemical and physical cues to enhance glial cell function and support axonal growth remains challenging. This study aimed to assess the impact of electrical stimulation (ES) using a conductive nerve conduit on sciatic nerve regeneration in a rat model with transection injury. The study involved the fabrication of conductive nerve conduits using silk fibroin and Au nanoparticles (AuNPs). Collagen hydrogel loaded with green fluorescent protein (GFP)-positive adipose-derived mesenchymal stem cells (ADSCs) served as the filling for the conduit. Both conductive and non-conductive conduits were applied with and without ES in rat models. Locomotor recovery was assessed using walking track analysis. Histological evaluations were performed using H&E, luxol fast blue staining and immunohistochemistry. Moreover, TEM analysis was conducted to distinguish various ultrastructural aspects of sciatic tissue. In the ES + conductive conduit group, higher S100 (p < 0.0001) and neurofilament (p < 0.001) expression was seen after 6 weeks. Ultrastructural evaluations showed that conductive scaffolds with ES minimized Wallerian degeneration. Furthermore, the conductive conduit with ES group demonstrated significantly increased myelin sheet thickness and decreased G. ratio compared to the autograft. Immunofluorescent images confirmed the presence of GFP-positive ADSCs by the 6th week. Locomotor recovery assessments revealed improved function in the conductive conduit with ES group compared to the control group and groups without ES. These results show that a Silk/AuNPs conduit filled with ADSC-seeded collagen hydrogel can function as a nerve conduit, aiding in the restoration of substantial gaps in the sciatic nerve with ES. Histological and locomotor evaluations indicated that ES had a greater impact on functional recovery compared to using a conductive conduit alone, although the use of conductive conduits did enhance the effects of ES.

Electrically Evoked Stapedius Reflex Measurements in Cochlear Implantation and its Application in the Postoperative Fitting Process.

Measuring the electrically evoked stapedius reflex during the fitting of cochlear implants (CIs) provides a reliable estimation of maximum comfort levels, resulting in the programming of the CI with high hearing comfort and good speech understanding. Detection of the stapedius reflex and the required stimulation level on each implant channel is already being performed during surgery, whereby intraoperative stapedius reflexes are observed through the surgical microscope. Intraoperative stapedius reflex detection is both an indicator that the auditory nerve is responding to electrical stimulation up to the brainstem and a test for the ability to perform postoperative stapedius reflex measurements. Postoperative stapedius reflex thresholds can be used to estimate upper stimulation levels in the CI fitting process. In particular, in children or patients unable to provide feedback on loudness perception, this method avoids inadequate stimulation with the CI, which can result in poor hearing performance. In addition, overstimulation can be avoided, which could even lead to refusal to use the device.

Enhancing the microbial advanced oxidation of P-nitrophenol in sediment through accelerating extracellular respiration with electrical stimulation.

Microbial advanced oxidation, a fundamental process for pollutant degradation in nature, is limited in efficiency by the weak respiration of indigenous microorganisms. In this study, an electric field was employed to enhance microbial respiration and facilitate the microbial advanced oxidation of p-nitrophenol (PNP) in simulated wetlands with alternation of anaerobic and aerobic conditions. With intermittent air aeration, an electric field of 0.8 V promoted extracellular electron transfer to increase Fe2+ generation through dissimilatory iron reduction and the production of hydroxyl radicals (•OH) through Fenton-like reactions. As a result, the PNP removal rate of the electrically-stimulated group was higher than that of the control (72.15 % vs 46.88 %). Multiple lines of evidence demonstrated that the electrically-induced polarization of respiratory enzymes expedited proton-coupled electron transfer within the respiratory chain to accelerate microbial advanced oxidation of PNP. The polarization of respiratory enzymes with the electric field hastened proton outflow to increase cell membrane potential for adenosine triphosphate (ATP) generation, which enhanced intracellular electron transportation to benefit reactive oxygen species generation. This study provided a new method to enhance microelectrochemical remediation of the contaminant in wetlands via the combination of intermittent air aeration.

Pediatric Intraoperative Electromyographic Responses at the Adductor Pollicis and Flexor Hallucis Brevis Muscles: A Prospective, Comparative Analysis.

BACKGROUND: Peripheral nerve stimulation with a train-of-four (TOF) pattern can be used intraoperatively to evaluate the depth of neuromuscular block and confirm recovery from neuromuscular blocking agents (NMBAs). Quantitative monitoring can be challenging in infants and children due to patient size, equipment technology, and limited access to monitoring sites. Although the adductor pollicis muscle is the preferred site of monitoring, the foot is an alternative when the hands are unavailable. However, there is little information on comparative evoked neuromuscular responses at those 2 sites. METHODS: Pediatric patients undergoing inpatient surgery requiring NMBA administration were studied after informed consent. Electromyographic (EMG) monitoring was performed simultaneously in each participant at the hand (ulnar nerve, adductor pollicis muscle) and the foot (posterior tibial nerve, flexor hallucis brevis muscle). RESULTS: Fifty patients with a mean age of 3.0 ± standard deviation (SD) 2.9 years were studied. The baseline first twitch amplitude (T1) of TOF at the foot (12.46 mV) was 4.47 mV higher than at the hand (P <.0001). The baseline TOF ratio (TOFR) before NMBA administration and the maximum TOFR after antagonism with sugammadex were not different at the 2 sites. The onset time until the T1 decreased to 10% or 5% of the baseline value (T1) was delayed by approximately 90 seconds (both P =.014) at the foot compared with the hand. The TOFR at the foot recovered (TOFR ≥0.9) 191 seconds later than when this threshold was achieved at the hand (P =.017). After antagonism, T1 did not return to its baseline value, a typical finding with EMG monitoring, but the fractional recovery (maximum T1 at recovery divided by the baseline T1) at the hand and foot was not different, 0.81 and 0.77, respectively (P =.68). The final TOFR achieved at recovery was approximately 100% and was not different between the 2 sites. CONCLUSIONS: Although this study in young children demonstrated the feasibility of TOF monitoring, interpretation of the depth of neuromuscular block needs to consider the delayed onset and the delayed recovery of TOFR at the foot compared to the hand. The delay in achieving these end points when monitoring the foot may impact the timing of tracheal intubation and assessment of adequate recovery of neuromuscular block to allow tracheal extubation (ie, TOFR ≥0.9).

Basal temporal language area revisited in Japanese language with a language function density map.

We revisited the anatomo-functional characteristics of the basal temporal language area (BTLA), first described by Lüders et al. (1986), using electrical cortical stimulation (ECS) in the context of Japanese language and semantic networks. We recruited 11 patients with focal epilepsy who underwent chronic subdural electrode implantation and ECS mapping with multiple language tasks for presurgical evaluation. A semiquantitative language function density map delineated the anatomo-functional characteristics of the BTLA (66 electrodes, mean 3.8 cm from the temporal tip). The ECS-induced impairment probability was higher in the following tasks, listed in a descending order: spoken-word picture matching, picture naming, Kanji word reading, paragraph reading, spoken-verbal command, and Kana word reading. The anterior fusiform gyrus (FG), adjacent anterior inferior temporal gyrus (ITG), and the anterior end where FG and ITG fuse, were characterized by stimulation-induced impairment during visual and auditory tasks requiring verbal output or not, whereas the middle FG was characterized mainly by visual input. The parahippocampal gyrus was the least impaired of the three gyri in the basal temporal area. We propose that the BTLA has a functional gradient, with the anterior part involved in amodal semantic processing and the posterior part, especially the middle FG in unimodal semantic processing.

Integrating Graphene Oxide-Hydrogels and Electrical Stimulation for Controlled Neurotrophic Factor Encapsulation: A Promising Approach for Efficient Nerve Tissue Regeneration.

Nerve growth factor (NGF) plays a crucial role in cellular growth and neurodifferentiation. To achieve significant neuronal regeneration and repair using in vitro NGF delivery, spatiotemporal control that follows the natural neuronal processes must be developed. Notably, a challenge hindering this is the uncontrolled burst release from the growth factor delivery systems. The rapid depletion of NGF reduces treatment efficacy, leading to poor cellular response. To address this, we developed a highly controllable system using graphene oxygen (GO) and GelMA hydrogels modulated by electrical stimulation. Our system showed superior control over the release kinetics, reducing the burst up 30-fold. We demonstrate that the system is also able to sequester and retain NGF up to 10-times more efficiently than GelMA hydrogels alone. Our controlled release system enabled neurodifferentiation, as revealed by gene expression and immunostaining analysis. The increased retention and reduced burst release from our system show a promising pathway for nerve tissue engineering research toward effective regeneration.

Effect of tetanic stimulation prior to train-of-four monitoring on the time to muscle response stabilization with neuromuscular blockade with rocuronium in patients aged 60 to 80 years: A prospective randomized controlled trial.

PURPOSE: To determine the effect of tetanic stimulation on the time to achieve stabilization of the T1 height, by acceleromyography train-of-four (TOF) ratio monitoring, in patients aged 60 to 80 years. METHODS: Randomized, prospective, single-blind, controlled trial in patients aged 60 to 80 years undergoing elective surgery under general anesthesia in two university hospitals in Brazil between December 2019 and March 2022. This trial was performed in accordance with the principles of the Helsinki Declaration and the guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II. Participants were randomly allocated by computer-generated numbers to receive tetanic stimulation (intervention group, n = 25) or not receive tetanic stimulation (control group, n = 25) to achieve T1 height stabilization on TOF ratio monitoring. The primary endpoint was to evaluate the effect of tetanic stimulation on the time to achieve stabilization of the T1 height. We also evaluated the effect on the onset time of rocuronium and time to recover from neuromuscular blockade with a single dose of rocuronium 0.6 mg.kg-1 with spontaneous recovery. RESULTS: There was no statistically significant difference between the groups in the time to T1 height stabilization (intervention: 4.3 [2.0-8.0] min; control: 5.8 [2.0-10.5] min; p = 0.202), onset time of the neuromuscular blocking agent (intervention: 1.9 [±0.7] min; control: 2.2 [±1.0] min; p = 0.219), or neuromuscular blockade recovery times to normalized TOF values of 0.7 (intervention: 106.1 [±37.2] min; control: 91.7 [±27.5] min; p = 0.295), 0.8 (intervention: 114.3 [±40.1] min; control: 97.8 [±28.9] min; p = 0.225), 0.9 (intervention: 126.5 [±44.0] min; control: 106.9 [±30.6] min; p = 0.153), and 1.0 (intervention: 138.3 [±43.4] min; control: 123.8 [±43.5] min; p = 0.425). CONCLUSION: The results of this study suggest that the recommendation to use tetanic stimulation to shorten the time to T1 height stabilization in neuromuscular monitoring did not alter the stabilization time of the T1 twitch or the pharmacodynamics of neuromuscular blockade with rocuronium in patients aged 60 to 80 years.

Peaglet: A user-friendly probabilistic Kernel density estimation of intracranial cortical and subcortical stimulation sites.

BACKGROUND: Data on human brain function obtained with direct electrical stimulation (DES) in neurosurgical patients have been recently integrated and combined with modern neuroimaging techniques, allowing a connectome-based approach fed by intraoperative DES data. Within this framework is crucial to develop reliable methods for spatial localization of DES-derived information to be integrated within the neuroimaging workflow. NEW METHOD: To this aim, we applied the Kernel Density Estimation for modelling the distribution of DES sites from different patients into the MNI space. The algorithm has been embedded in a MATLAB-based User Interface, Peaglet. It allows an accurate probabilistic weighted and unweighted estimation of DES sites location both at cortical level, by using shortest path calculation along the brain 3D geometric topology, and subcortical level, by using a volume-based approach. RESULTS: We applied Peaglet to investigate spatial estimation of cortical and subcortical stimulation sites provided by recent brain tumour studies. The resulting NIfTI maps have been anatomically investigated with neuroimaging open-source tools. COMPARISON WITH EXISTING METHODS: Peaglet processes differently cortical and subcortical data following their distinguishing geometrical features, increasing anatomical specificity of DES-related results and their reliability within neuroimaging environments. CONCLUSIONS: Peaglet provides a robust probabilistic estimation of the cortical and subcortical distribution of DES sites going beyond a region of interest approach, respecting cortical and subcortical intrinsic geometrical features. Results can be easily integrated within the neuroimaging workflow to drive connectomic analysis.

Wired for Success: Probing the Effect of Tissue-Engineered Neural Interface Substrates on Cell Viability.

This study investigates the electrochemical behavior of GelMA-based hydrogels and their interactions with PC12 neural cells under electrical stimulation in the presence of conducting substrates. Focusing on indium tin oxide (ITO), platinum, and gold mylar substrates supporting conductive scaffolds composed of hydrogel, graphene oxide, and gold nanorods, we explored how the substrate materials affect scaffold conductivity and cell viability. We examined the impact of an optimized electrical stimulation protocol on the PC12 cell viability. According to our findings, substrate selection significantly influences conductive hydrogel behavior, affecting cell viability and proliferation as a result. In particular, the ITO substrates were found to provide the best support for cell viability with an average of at least three times higher metabolic activity compared to platinum and gold mylar substrates over a 7 day stimulation period. The study offers new insights into substrate selection as a platform for neural cell stimulation and underscores the critical role of substrate materials in optimizing the efficacy of neural interfaces for biomedical applications. In addition to extending existing work, this study provides a robust platform for future explorations aimed at tailoring the full potential of tissue-engineered neural interfaces.

Timing-dependent synergies between motor cortex and posterior spinal stimulation in humans.

Volitional movement requires descending input from the motor cortex and sensory feedback through the spinal cord. We previously developed a paired brain and spinal electrical stimulation approach in rats that relies on convergence of the descending motor and spinal sensory stimuli in the cervical cord. This approach strengthened sensorimotor circuits and improved volitional movement through associative plasticity. In humans, it is not known whether posterior epidural spinal cord stimulation targeted at the sensorimotor interface or anterior epidural spinal cord stimulation targeted within the motor system is effective at facilitating brain evoked responses. In 59 individuals undergoing elective cervical spine decompression surgery, the motor cortex was stimulated with scalp electrodes and the spinal cord was stimulated with epidural electrodes, with muscle responses being recorded in arm and leg muscles. Spinal electrodes were placed either posteriorly or anteriorly, and the interval between cortex and spinal cord stimulation was varied. Pairing stimulation between the motor cortex and spinal sensory (posterior) but not spinal motor (anterior) stimulation produced motor evoked potentials that were over five times larger than brain stimulation alone. This strong augmentation occurred only when descending motor and spinal afferent stimuli were timed to converge in the spinal cord. Paired stimulation also increased the selectivity of muscle responses relative to unpaired brain or spinal cord stimulation. Finally, clinical signs suggest that facilitation was observed in both injured and uninjured segments of the spinal cord. The large effect size of this paired stimulation makes it a promising candidate for therapeutic neuromodulation. KEY POINTS: Pairs of stimuli designed to alter nervous system function typically target the motor system, or one targets the sensory system and the other targets the motor system for convergence in cortex. In humans undergoing clinically indicated surgery, we tested paired brain and spinal cord stimulation that we developed in rats aiming to target sensorimotor convergence in the cervical cord. Arm and hand muscle responses to paired sensorimotor stimulation were more than five times larger than brain or spinal cord stimulation alone when applied to the posterior but not anterior spinal cord. Arm and hand muscle responses to paired stimulation were more selective for targeted muscles than the brain- or spinal-only conditions, especially at latencies that produced the strongest effects of paired stimulation. Measures of clinical evidence of compression were only weakly related to the paired stimulation effect, suggesting that it could be applied as therapy in people affected by disorders of the central nervous system.

Feasibility of endovascular stimulation of the femoral nerve using a stent-mounted electrode array.

Objective.Electrical stimulation of peripheral nerves has long been a treatment option to restore impaired neural functions that cannot be restored by conventional pharmacological therapies. Endovascular neurostimulation with stent-mounted electrode arrays is a promising and less invasive alternative to traditional implanted electrodes, which typically require invasive implantation surgery. In this study, we investigated the feasibility of endovascular stimulation of the femoral nerve using a stent-mounted electrode array and compared its performance to that of a commercially available pacing catheter.Approach.In acute animal experiments, a pacing catheter was implanted unilaterally in the femoral artery to stimulate the femoral nerve in a bipolar configuration. Electromyogram of the quadriceps and electroneurogram of a distal branch of the femoral nerve were recorded. After retrieval of the pacing catheter, a bipolar stent-mounted electrode array was implanted in the same artery and the recording sessions were repeated.Main Results.Stimulation of the femoral nerve was feasible with the stent-electrode array. Although the threshold stimulus intensities required with the stent-mounted electrode array (at 100-500µs increasing pulse width, 2.17 ± 0.87 mA-1.00 ± 0.11 mA) were more than two times higher than the pacing catheter electrodes (1.05 ± 0.48 mA-0.57 ± 0.28 mA), we demonstrated that, by reducing the stimulus pulse width to 100µs, the threshold charge per phase and charge density can be reduced to 0.22 ± 0.09µC and 24.62 ± 9.81µC cm-2, which were below the tissue-damaging limit, as defined by the Shannon criteria.Significance.The present study is the first to reportin vivofeasibility and efficiency of peripheral nerve stimulation using an endovascular stent-mounted electrode array.

Intracochlear Recording of Electrocochleography During and After Cochlear Implant Insertion Dependent on the Location in the Cochlea.

To preserve residual hearing during cochlear implant (CI) surgery it is desirable to use intraoperative monitoring of inner ear function (cochlear monitoring). A promising method is electrocochleography (ECochG). Within this project the relations between intracochlear ECochG recordings, position of the recording contact in the cochlea with respect to anatomy and frequency and preservation of residual hearing were investigated. The aim was to better understand the changes in ECochG signals and whether these are due to the electrode position in the cochlea or to trauma generated during insertion. During and after insertion of hearing preservation electrodes, intraoperative ECochG recordings were performed using the CI electrode (MED-EL). During insertion, the recordings were performed at discrete insertion steps on electrode contact 1. After insertion as well as postoperatively the recordings were performed at different electrode contacts. The electrode location in the cochlea during insertion was estimated by mathematical models using preoperative clinical imaging, the postoperative location was measured using postoperative clinical imaging. The recordings were analyzed from six adult CI recipients. In the four patients with good residual hearing in the low frequencies the signal amplitude rose with largest amplitudes being recorded closest to the generators of the stimulation frequency, while in both cases with severe pantonal hearing losses the amplitude initially rose and then dropped. This might be due to various reasons as discussed in the following. Our results indicate that this approach can provide valuable information for the interpretation of intracochlearly recorded ECochG signals.

Neuromuscular electrical stimulation for physical function maintenance during hematopoietic stem cell transplantation: Study protocol.

Hematopoietic stem cell transplantation is a common life-saving treatment for hematologic malignancies, though can lead to long-term functional impairment, fatigue, muscle atrophy, with decreased quality of life. Although traditional exercise has helped reduce these effects, it is inconsistently recommended and infrequently maintained, and most patients remain sedentary during and after treatment. There is need for alternative rehabilitation strategies, like neuromuscular electrical stimulation, that may be more amenable to the capabilities of hematopoietic stem cell transplant recipients. Patients receiving autologous HCT are being enroled in a randomized controlled trial with 1:1 (neuromuscular electrical stimulation:sham) design stratified by diagnosis and sex. Physical function, body composition, quality of life, and fatigue are assessed prior to hematopoietic stem cell transplant (prior to initiating preparatory treatment) and 24±5 days post hematopoietic stem cell transplant (Follow-up 1); physical function and quality of life are also assessed 6-months post hematopoietic stem cell transplant (Follow-up 2). The primary outcome is between-group difference in the 6-minute walk test change scores (Follow-up 1-Pre-transplant; final enrolment goal N = 23/group). We hypothesize that 1) neuromuscular electrical stimulation will attenuate hematopoietic stem cell transplant-induced adverse effects on physical function, muscle mass, quality of life, and fatigue compared to sham at Follow-up 1, and 2) Pre-transplant physical function will significantly predict fatigue and quality of life at Follow-up 2. We will also describe feasibility and acceptability of neuromuscular electrical stimulation during hematopoietic stem cell transplant. This proposal will improve rehabilitative patient care and quality of life by determining efficacy and feasibility of a currently underutilized therapeutic strategy aimed at maintaining daily function and reducing the impact of a potent and widely used cancer treatment. This trial is registered with clinicaltrials.gov (NCT04364256).

Electrical Stimulation-Based Twitch Exercise Suppresses Progression of Immobilization-Induced Muscle Fibrosis via Downregulation of PGC-1?/VEGF Pathway.

This study aimed to determine whether electrical stimulation-based twitch exercise is effective in inhibiting the progression of immobilization-induced muscle fibrosis. 19 Wistar rats were randomly divided into a control group (n=6), an immobilization group (n=6; with immobilization only), and a Belt group (n=7; with immobilization and twitch exercise through the belt electrode device, beginning 2 weeks after immobilization). The bilateral soleus muscles were harvested after the experimental period. The right soleus muscles were used for histological analysis, and the left soleus muscles were used for biochemical and molecular biological analysis. As a result, in the picrosirius red images, the perimysium and endomysium were thicker in both the immobilization and Belt groups compared to the control group. However, the perimysium and endomysium thickening were suppressed in the Belt group. The hydroxyproline content and alpha-SMA, TGF-beta1, and HIF-1alpha mRNA expressions were significantly higher in the immobilization and belt groups than in the control group. These expressions were significantly lower in the Belt group than in the immobilization group. The capillary-to-myofiber ratio and the mRNA expressions of VEGF and PGC-1alpha were significantly lower in the immobilization and belt groups than in the control group, these were significantly higher in the Belt group than in the immobilization group. From these results, Electrical stimulation-based twitch exercise using the belt electrode device may prevent the progression of immobilization-induced muscle fibrosis caused by downregulating PGC-1alpha/VEGF pathway, we surmised that this intervention strategy might be effective against the progression of muscle contracture. Keywords: Immobilization, Skeletal muscle, Fibrosis, Electrical stimulation-based twitch exercise, PGC-1alpha/VEGF pathway.

New stimulation procedures for language mapping in stereo-EEG.

OBJECTIVE: Cortical intracerebral electrical stimulation is an important tool for language mapping in the presurgical work-up of patients with drug-resistant focal epilepsy. Language mapping with stereo-electroencephalography (EEG) is usually performed by high-frequency stimulations (HFS: 50 Hz), whereas low-frequency stimulations (LFS: 1 Hz) are usually considered useful for primary cortices mapping. Little is known in literature about "intermediate" frequencies (IFS: 6-15 Hz). Our objective is to explore the clinical usefulness of IFS in language mapping and identify factors, beyond the electrical parameters, that impact the mapping. METHODS: We studied 23 patients submitted to stereo-EEG for presurgical evaluation. Language mapping was performed in the anterior, posterior and/or basal language region of the dominant hemisphere for language. We included all contact positions within these regions stimulated by HFS (50 Hz, 5 s, 1-3 mA) and IFS (6-15 Hz, 15 s, 5 mA). We compared the capability of both stimulation methods to induce a language deficit without afterdischarges (ADs), and we analyzed factors related to clinical examination, region, and stimulation technique by multivariate analysis. RESULTS: A total of 211 stimulations (98 HFS, 113 IFS) in 70 cortical sites within the anterior (84 stimulations), posterior (137), and basal language region (60) were included. IFS induced more frequently language deficits not associated to AD compared to HFS (37.1% vs 25.7%, p = .0043), whereas HFS provoked more diffuse AD (34.7% vs 15.0%, p = .001). Investigating multiple language functions increased the probability of revealing a deficit (odds ratio [OR] 3.16, p = .0016), independently of the stimulation method. SIGNIFICANCE: IFS are valuable for language mapping, thereby improving the probability of inducing a clinical deficit not accompanied by an AD. The completeness of the clinical examination independently affects the sensitivity of the mapping. IFS are a new tool with potential usefulness for the cortical mapping of other associative cortical regions.

In a porcine model of implantable pacemakers for pediatric unilateral diaphragm paralysis, the phrenic nerve is the best target.

BACKGROUND: A frequent complication of Fontan operations is unilateral diaphragmatic paresis, which leads to hemodynamic deterioration of the Fontan circulation. A potential new therapeutic option is the unilateral diaphragmatic pacemaker. In this study, we investigated the most effective stimulation location for a potential fully implantable system in a porcine model. METHODS: Five pigs (20.8 ± 0.95 kg) underwent implantation of a customized cuff electrode placed around the right phrenic nerve. A bipolar myocardial pacing electrode was sutured adjacent to the motor point and peripherally at the costophrenic angle (peripheral diaphragmatic muscle). The electrodes were stimulated 30 times per minute with a pulse duration of 200 µs and a stimulation time of 300 ms. Current intensity was the only variable changed during the experiment. RESULTS: Effective stimulation occurred at 0.26 ± 0.024 mA at the phrenic nerve and 7 ± 1.22 mA at the motor point, a significant difference in amperage (p = 0.005). Even with a maximum stimulation of 10 mA at the peripheral diaphragm muscle, however, no effective stimulation was observed. CONCLUSION: The phrenic nerve seems to be the best location for direct stimulation by a unilateral thoracic diaphragm pacemaker in terms of the required amperage level in a porcine model.

Surface electrical stimulation of the auditory cortex preserves efferent medial olivocochlear neurons and reduces cochlear traits of age-related hearing loss.

The auditory cortex is the source of descending connections providing contextual feedback for auditory signal processing at almost all levels of the lemniscal auditory pathway. Such feedback is essential for cognitive processing. It is likely that corticofugal pathways are degraded with aging, becoming important players in age-related hearing loss and, by extension, in cognitive decline. We are testing the hypothesis that surface, epidural stimulation of the auditory cortex during aging may regulate the activity of corticofugal pathways, resulting in modulation of central and peripheral traits of auditory aging. Increased auditory thresholds during ongoing age-related hearing loss in the rat are attenuated after two weeks of epidural stimulation with direct current applied to the surface of the auditory cortex for two weeks in alternate days (Fernández del Campo et al., 2024). Here we report that the same cortical electrical stimulation protocol induces structural and cytochemical changes in the aging cochlea and auditory brainstem, which may underlie recovery of age-degraded auditory sensitivity. Specifically, we found that in 18 month-old rats after two weeks of cortical electrical stimulation there is, relative to age-matched non-stimulated rats: a) a larger number of choline acetyltransferase immunoreactive neuronal cell body profiles in the ventral nucleus of the trapezoid body, originating the medial olivocochlear system.; b) a reduction of age-related dystrophic changes in the stria vascularis; c) diminished immunoreactivity for the pro-inflammatory cytokine TNFα in the stria vascularis and spiral ligament. d) diminished immunoreactivity for Iba1 and changes in the morphology of Iba1 immunoreactive cells in the lateral wall, suggesting reduced activation of macrophage/microglia; d) Increased immunoreactivity levels for calretinin in spiral ganglion neurons, suggesting excitability modulation by corticofugal stimulation. Altogether, these findings support that non-invasive neuromodulation of the auditory cortex during aging preserves the cochlear efferent system and ameliorates cochlear aging traits, including stria vascularis dystrophy, dysregulated inflammation and altered excitability in primary auditory neurons.

[Progress of electrical stimulation to promote peripheral nerve regeneration].

This study reviews the latest progress on the research of electrical stimulation（ES） in peripheral nerve regeneration, summarizes the parameters in preclinical experiments and discusses the effect on nerve regeneration. A detailed description is given in the study of conditioning electrical stimulation and nerve conduit scaffolding technology combined with ES, which have been hotly researched in recent years.

Synergistic effects of graphene microgrooves and electrical stimulation on M2 macrophage polarization.

Macrophages play a crucial role in host response and wound healing, with M2 polarization contributing to the reduction of foreign-body reactions induced by the implantation of biomaterials and promoting tissue regeneration. Electrical stimulation (ES) and micropatterned substrates have a significant impact on the macrophage polarization. However, there is currently a lack of well-established cell culture platforms for studying the synergistic effects of these two factors. In this study, we prepared a graphene free-standing substrate with 20 µm microgrooves using capillary forces induced by water evaporation. Subsequently, we established an ES cell culture platform for macrophage cultivation by integrating a self-designed multi-well chamber cell culture device. We observed that graphene microgrooves, in combination with ES, significantly reduce cell spreading area and circularity. Results from immunofluorescence, ELISA, and flow cytometry demonstrate that the synergistic effect of graphene microgrooves and ES effectively promotes macrophage M2 phenotypic polarization. Finally, RNA sequencing results reveal that the synergistic effects of ES and graphene microgrooves inhibit the macrophage actin polymerization and the downstream PI3K signaling pathway, thereby influencing the phenotypic transition. Our results demonstrate the potential of graphene-based microgrooves and ES to synergistically modulate macrophage polarization, offering promising applications in regenerative medicine.

Comparative validation of automated presurgical tractography based on constrained spherical deconvolution and diffusion tensor imaging with direct electrical stimulation.

OBJECTIVES: Accurate presurgical brain mapping enables preoperative risk assessment and intraoperative guidance. This cross-sectional study investigated whether constrained spherical deconvolution (CSD) methods were more accurate than diffusion tensor imaging (DTI)-based methods for presurgical white matter mapping using intraoperative direct electrical stimulation (DES) as the ground truth. METHODS: Five different tractography methods were compared (three DTI-based and two CSD-based) in 22 preoperative neurosurgical patients undergoing surgery with DES mapping. The corticospinal tract (CST, N = 20) and arcuate fasciculus (AF, N = 7) bundles were reconstructed, then minimum distances between tractograms and DES coordinates were compared between tractography methods. Receiver-operating characteristic (ROC) curves were used for both bundles. For the CST, binary agreement, linear modeling, and posthoc testing were used to compare tractography methods while correcting for relative lesion and bundle volumes. RESULTS: Distance measures between 154 positive (functional response, pDES) and negative (no response, nDES) coordinates, and 134 tractograms resulted in 860 data points. Higher agreement was found between pDES coordinates and CSD-based compared to DTI-based tractograms. ROC curves showed overall higher sensitivity at shorter distance cutoffs for CSD (8.5 mm) compared to DTI (14.5 mm). CSD-based CST tractograms showed significantly higher agreement with pDES, which was confirmed by linear modeling and posthoc tests (PFWE < .05). CONCLUSIONS: CSD-based CST tractograms were more accurate than DTI-based ones when validated using DES-based assessment of motor and sensory function. This demonstrates the potential benefits of structural mapping using CSD in clinical practice.