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Objective To investigate the application effect of transcutaneous electrical acupoint stimulation (TEAS) combined with propofol in painless gastrointestinal endoscopy. Methods A total of 105 patients who underwent gastrointestinal endoscopy were randomly divided into propofol+fentanyl group (P+F group), propofol+TEAS group (P+T group), and propofol+placebo-TEAS group (P+P group), with 35 patients in each group. All patients were induced to deep sedation by the anesthesiologist using propofol before gastroscopy; the patients in the P+F group were given intravenously injected fentanyl 50 μg before gastroscopy, those in the P+T group received placement of electrodes at the acupoints at 30 minutes before examination and were given electrical stimulation till the end of the examination, and those in the P+P group received placement of electrodes at the acupoints alone without electrical stimulation. The patients were recorded in terms of pain score and the amount of propofol used du-ring examination, the time to recovery from anesthesia after examination, and the incidence rate of adverse reactions during or after examination, as well as the degree of satisfaction among patients and physicians. Results Compared with the P+P group, the P+F and P+T groups had a significant reduction in pain score (H=23.16,P0.05), while the P+F group had significantly higher degrees of vertigo, nausea, and vomiting than the other two groups (H=40.97-44.79,P

Background:: Deep brain stimulation of the central thalamus (CT-DBS) has potential for modulating states of consciousness, but it can also trigger electrographic seizures, including poly-spike-wave trains (PSWT). Objectives:: To report the probability of inducing PSWTs during CT-DBS in awake, freely-moving mice. Methods:: Mice were implanted with electrodes to deliver unilateral and bilateral CT-DBS at different frequencies while recording electroencephalogram (EEG). We titrated stimulation current by gradually increasing it at each frequency until a PSWT appeared. Subsequent stimulations to test arousal modulation were performed at the current one step below the current that caused a PSWT during titration. Results:: In 2.21% of the test stimulations (10 out of 12 mice), CT-DBS caused PSWTs at currents lower than the titrated current, including currents as low as 20 μA. Conclusion:: Our study found a small but significant probability of inducing PSWTs even after titration and at relatively low currents. EEG should be closely monitored for electrographic seizures when performing CT-DBS in both research and clinical settings.

Context: Exercising intrinsic foot muscles (IFMs) can improve dynamic balance and foot posture. The exercises are not intuitive and electrotherapy (neuromuscular electrical stimulation [NMES]) has been suggested to help individuals execute the exercises. The aim of this study was to evaluate the effects of training IFM program on dynamic balance and foot posture and compare traditional training methods (TRAIN) with traditional training plus NMES on the perceived workload of the exercises, balance, and foot posture. Design: Randomized controlled trial. Methods: Thirty-nine participants were randomized to control, TRAIN, or NMES. TRAIN and NMES performed IFM exercises daily for 4 weeks; NMES received electrotherapy during the first 2 weeks of training. The Y-Balance test and arch height index were measured in all participants at baseline. The training groups were measured again at 2 weeks; all participants were measured at 4 weeks and 8 weeks, after 4 weeks of no training. Perceived workload (National Aeronautics and Space Administration Task Load Index) of exercises was assessed throughout the first 2 weeks and at 4 weeks. Results: A 4-week IFM training program demonstrated increases in Y-Balance (P =.01) for TRAIN and in arch height index (seated P =.03; standing P =.02) for NMES, relative to baseline. NMES demonstrated improvement in Y-Balance (P =.02) and arch height index standing (P =.01) at 2 weeks. There were no significant differences between the training groups. Groups were similar in the number responding to exercises in excess of minimal detectable change on all clinical measures. Perceived workload of the exercises decreased during the first 2 weeks of training (P =.02), and more notably at 4 weeks (P <.001). The groups did not differ in how they perceived the workload. Conclusions: A 4-week IFM training program improved dynamic balance and foot posture. Adding NMES in early phases of training provided early improvement in dynamic balance and foot posture, but did not affect perceived workload. [ABSTRACT FROM AUTHOR]

Context: Pulsed current and kilohertz frequency alternating current are 2 types of neuromuscular electrical stimulation (NMES) currents often used by clinicians during rehabilitation. However, the low methodological quality and the different NMES parameters and protocols used in several studies might explain their inconclusive results in terms of their effects in the evoked torque and the discomfort level. In addition, the neuromuscular efficiency (ie, the NMES current type that evokes the highest torque with the lowest current intensity) has not been established yet. Therefore, our objective was to compare the evoked torque, current intensity, neuromuscular efficiency (evoked torque/current intensity ratio), and discomfort between pulsed current and kilohertz frequency alternating current in healthy people. Design: A double-blind, randomized crossover trial. Methods: Thirty healthy men (23.2 [4.5] y) participated in the study. Each participant was randomized to 4 current settings: 2 kilohertz frequency alternating currents with 2.5 kHz of carrier frequency and similar pulse duration (0.4 ms) and burst frequency (100 Hz) but with different burst duty cycles (20% and 50%) and burst durations (2 and 5 ms); and 2 pulsed currents with similar pulse frequency (100 Hz) and different pulse duration (2 and 0.4 ms). The evoked torque, current intensity at the maximal tolerated intensity, neuromuscular efficiency, and discomfort level were evaluated. Results: Both pulsed currents generated higher evoked torque than the kilohertz frequency alternating currents, despite the similar between-currents discomfort levels. The 2 ms pulsed current showed lower current intensity and higher neuromuscular efficiency compared with both alternated currents and with the 0.4 ms pulsed current. Conclusions: The higher evoked torque, higher neuromuscular efficiency, and similar discomfort of the 2 ms pulsed current compared with 2.5-kHz frequency alternating current suggests this current as the best choice for clinicians to use in NMES-based protocols. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) is an effective therapy for various neurologic and neuropsychiatric disorders, involving chronic implantation of electrodes into target brain regions for electrical stimulation delivery. Despite its safety and efficacy, DBS remains an underutilized therapy. Advances in the field of DBS, including in technology, mechanistic understanding, and applications have the potential to expand access and use of DBS, while also improving clinical outcomes. Developments in DBS technology, such as MRI compatibility and bidirectional DBS systems capable of sensing neural activity while providing therapeutic stimulation, have enabled advances in our understanding of DBS mechanisms and its application. In this review, we summarize recent work exploring DBS modulation of target networks. We also cover current work focusing on improved programming and the development of novel stimulation paradigms that go beyond current standards of DBS, many of which are enabled by sensing-enabled DBS systems and have the potential to expand access to DBS.

The current cardiac pacemakers are battery dependent, and the pacing leads are prone to introduce valve damage and infection, plus a complete pacemaker retrieval is needed for battery replacement. Despite the reported wireless bioelectronics to pace the epicardium, open-chest surgery (thoracotomy) is required to implant the device, and the procedure is invasive, requiring prolonged wound healing and health care burden. We hereby demonstrate a fully biocompatible wireless microelectronics with a self-assembled design that can be rolled into a lightweight microtubular pacemaker for intravascular implantation and pacing. The radio frequency was used to transfer energy to the microtubular pacemaker for electrical stimulation. We show that this pacemaker provides effective pacing to restore cardiac contraction from a nonbeating heart and have the capacity to perform overdrive pacing to augment blood circulation in an anesthetized pig model. Thus, this microtubular pacemaker paves the way for the minimally invasive implantation of leadless and battery-free microelectronics.

BACKGROUND: Enteric neuropathies, which result from abnormalities of the enteric nervous system, are associated with significant morbidity and high health-care costs, but current treatments are unsatisfactory. Cell-based therapy offers an innovative approach to replace the absent or abnormal enteric neurons and thereby restore gut function. METHODS: Enteric neuronal stem cells (ENSCs) were isolated from the gastrointestinal tract of Wnt1-Cre;R26tdTomato mice and generated neurospheres (NS). NS transplants were performed via injection into the mid-colon mesenchyme of nNOS-/- mouse, a model of colonic dysmotility, using either 1 (n = 12) or 3 (n = 12) injections (30 NS per injection) targeted longitudinally 1-2 mm apart. Functional outcomes were assessed up to 6 weeks later using electromyography (EMG), electrical field stimulation (EFS), optogenetics, and by measuring colorectal motility. RESULTS: Transplanted ENSCs formed nitrergic neurons in the nNOS-/- recipient colon. Multiple injections of ENSCs resulted in a significantly larger area of coverage compared to single injection alone and were associated with a marked improvement in colonic function, demonstrated by (1) increased colonic muscle activity by EMG recording, (2) faster rectal bead expulsion, and (3) increased fecal pellet output in vivo. Organ bath studies revealed direct neuromuscular communication by optogenetic stimulation of channelrhodopsin-expressing ENSCs and restoration of smooth muscle relaxation in response to EFS. CONCLUSIONS: These results demonstrate that transplanted ENSCs can form effective neuromuscular connections and improve colonic motor function in a model of colonic dysmotility, and additionally reveal that multiple sites of cell delivery led to an improved response, paving the way for optimized clinical trial design.

A dual-responsive hydrogel drug reservoir responding to body temperature and electrical stimulation achieves high drug release efficiency at 37 °C and efficient transdermal delivery. The Zn battery-driven iontophoresis results in an effective treatment of atopic dermatitis with the release of dexamethasone. This work provides a non-invasive treatment modality for chronic epidermal diseases that require precise drug delivery. [Display omitted] • Polyelectrolyte hydrogel shows thermal-electrochemical dual-responsive drug release. • Wearable Zn battery-powered iontophoresis for transdermal delivery with enhanced efficacy. • Effective treatment of atopic dermatitis in mice is achieved. Atopic dermatitis is a chronic, inflammation skin disease that remains a major public health challenge. The current drug-loading hydrogel dressings offer numerous benefits with enhanced loading capacity and a moist-rich environment. However, their development is still limited by the accessibility of a suitable driven source outside the clinical environment for precise control over transdermal delivery kinetics. Here, we prepare a sulfonated poly(3,4-ethylenedioxythiophene) (PEDOT) polyelectrolyte hydrogel drug reservoir that responds to different stimuli-both endogenous cue (body temperature) and exogenous cue (electrical stimulation), for wearable on-demand transdermal delivery with enhanced efficacy. Functioned as both the drug reservoir and cathode in a Zn battery-powered iontophoresis patch, this dual-responsive hydrogel achieves high drug release efficiency (68.4 %) at 37 °C. Evaluation in hairless mouse skin demonstrates the efficacy of this technology by facilitating transdermal transport of 12.2 μg cm−2 dexamethasone phosphate when discharged with a 103 Ω external resistor for 3 h. The Zn battery-driven iontophoresis results in an effective treatment of atopic dermatitis, displaying reductions in epidermal thickness, mast cell infiltration inhibition, and a decrease in IgE levels. This work provides a new treatment modality for chronic epidermal diseases that require precise drug delivery in a non-invasive way. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament injury prevention should focus primarily on reduction of the knee abduction moment (KAM) in landing tasks. Gluteus medius and hamstring forces are considered to decrease KAM during landing. The effects of different muscle stimulations on KAM reduction were compared using 2 electrode sizes (standard 38 cm2 and half size 19 cm2) during a landing task. Twelve young healthy female adults (22.3 [3.6] y, 1.62 [0.02] m, 50.2 [4.7] kg) were recruited. KAM was calculated under 3 conditions of muscle stimulation (gluteus medius, biceps femoris, and both gluteus medius, and biceps femoris) using 2 electrode sizes, respectively versus no stimulation during a landing task. A repeated-measures analysis of variance determined that KAM differed significantly among stimulation conditions and post hoc analysis revealed that KAM was significantly decreased in conditions of stimulating either the gluteus medius (P <.001) or the biceps femoris (P <.001) with the standard electrode size, and condition of stimulating both gluteus medius and biceps femoris with half-size electrode (P =.012) when compared with the control condition. Therefore, stimulation on the gluteus medius, the biceps femoris, or both muscles could be implemented for the examination of anterior cruciate ligament injury potential. [ABSTRACT FROM AUTHOR]

Abstract Background Central neuropathic pain after foramen magnum decompression (FMD) for Chiari malformation type 1 (CM-1) with syringomyelia can be residual and refractory. Here we present a case of refractory central neuropathic pain after FMD in a CM-1 patient with syringomyelia who achieved improvements in pain following spinal cord stimulation (SCS) using fast-acting sub-perception therapy (FAST™). Case presentation A 76-year-old woman presented with a history of several years of bilateral upper extremity and chest-back pain. CM-1 and syringomyelia were diagnosed. The pain proved drug resistant, so FMD was performed for pain relief. After FMD, magnetic resonance imaging showed shrinkage of the syrinx. Pain was relieved, but bilateral finger, upper arm and thoracic back pain flared-up 10 months later. Due to pharmacotherapy resistance, SCS was planned for the purpose of improving pain. A percutaneous trial of SCS showed no improvement of pain with conventional SCS alone or in combination with Contour™, but the combination of FAST™ and Contour™ did improve pain. Three years after FMD, percutaneous leads and an implantable pulse generator were implanted. The program was set to FAST™ and Contour™. After implantation, pain as assessed using the McGill Pain Questionnaire and visual analog scale was relieved even after reducing dosages of analgesic. No adverse events were encountered. Conclusion Percutaneously implanted SCS using FAST™ may be effective for refractory pain after FMD for CM-1 with syringomyelia.

Changes in performance caused by positive and negative expectations (i.e., placebo and nocebo responses) were found to play an important role in many aspects of motor performance. This study aimed to test the impact of placebo/nocebo responses and the assumed moderating role of dispositional optimism and anxiety on proprioceptive accuracy, an essential aspect of motor functions. 78 undergraduate university students completed questionnaires assessing dispositional optimism, state anxiety, and motivation to cooperate, then were randomly assigned to three experimental groups. A sham subliminal electric stimulation was applied with claimed positive (placebo group, n = 26), negative (nocebo group, n = 26) or neutral (control group, n = 26) impact on proprioceptive accuracy. Proprioceptive accuracy was measured with active and passive versions of the Joint Position Reproduction task before and after the intervention. Expected and perceived changes in performance were also assessed; changes in state anxiety, optimism, and motivation to cooperate were used as control variables (covariates). Mixed analyses of variance indicated that the experimental manipulation did not affect actual proprioceptive accuracy but impacted expected and perceived performance. Adding the covariates to the models did not substantially change the results. Further, no significant association emerged between actual and perceived change in performance in the active test, and only a weak correlation was found in the passive test. Expected performance did not predict actual performance but predicted perceived performance in both tasks. The results suggest that only perceived (subjective) aspects of proprioceptive accuracy are susceptible to placebo and nocebo interventions. [ABSTRACT FROM AUTHOR]

Background: Transcutaneous spinal stimulation (TSS) and neuromuscular electrical stimulation (NMES) can facilitate self-assisted standing in individuals with paralysis. However, individual variability in responses to each modality may limit their effectiveness in generating the necessary leg extension force for full body weight standing. To address this challenge, we proposed combining TSS and NMES to enhance leg extensor muscle activation, with optimizing timing adjustment to maximize the interaction between the two modalities. Methods: To assess the effects of TSS and NMES on knee extension and plantarflexion force, ten neurologically intact participants underwent three conditions: (1) TSS control, (2) NMES control, and (3) TSS + NMES. TSS was delivered between the T10 and L2 vertebrae, while NMES was delivered to the skin over the right knee extensors and plantarflexors. TSS and NMES were administered using a 15 Hz train of three 0.5 ms biphasic pulses. During the TSS + NMES condition, the timing between modalities was adjusted in increments of ¼ the interval within a 15 Hz frequency, i.e., 66, 49.5, 33, 16.5, and 1 ms. Results: NMES combined with TSS, produced synergistic effects even on non-targeted muscle groups, thereby promoting leg extension across multiple joints in the kinematic chain. The sequence of NMES or TSS trains relative to each other did not significantly impact motor output. Notably, a delay of 16.5 to 49.5 ms between interleaved TSS and NMES pulses, each delivered at 15 Hz, results in more robust and synergistic responses in knee extensors and plantarflexors. Conclusions: By adjusting the timing between TSS and NMES, we can optimize the combined use of these modalities for functional restoration. Our findings highlight the potential of integrated TSS and NMES protocols to enhance motor function, suggesting promising avenues for therapeutic applications, particularly in the rehabilitation of individuals with SCI. [ABSTRACT FROM AUTHOR]

Timing cues such as interaural time differences (ITDs) and temporal pitch are pivotal for sound localization and source segregation, but their perception is degraded in cochlear-implant (CI) listeners as compared to normal-hearing listeners. In multi-electrode stimulation, intra-aural channel interactions between electrodes are assumed to be an important factor limiting access to those cues. The monaural asynchrony of stimulation timing across electrodes is assumed to mediate the amount of these interactions. This study investigated the effect of the monaural temporal electrode asynchrony (mTEA) between two electrodes, applied similarly in both ears, on ITD-based left/right discrimination sensitivity in five CI listeners, using pulse trains with 100 pulses per second and per electrode. Forward-masked spatial tuning curves were measured at both ears to find electrode separations evoking controlled degrees of across-electrode masking. For electrode separations smaller than 3 mm, results showed an effect of mTEA. Patterns were u/v-shaped, consistent with an explanation in terms of the effective pulse rate that appears to be subject to the well-known rate limitation in electric hearing. For separations larger than 7 mm, no mTEA effects were observed. A comparison to monaural rate-pitch discrimination in a separate set of listeners and in a matched setup showed no systematic differences between percepts. Overall, an important role of the mTEA in both binaural and monaural dual-electrode stimulation is consistent with a monaural pulse-rate limitation whose effect is mediated by channel interactions. Future CI stimulation strategies aiming at improved timing-cue encoding should minimize the stimulation delay between nearby electrodes that need to be stimulated successively. [ABSTRACT FROM AUTHOR]

Introduction: Proof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS). Methods: Participants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits. Results: 34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge's g = -3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements. Conclusions: These results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05205915?tab= results, identifier NCT05205915. [ABSTRACT FROM AUTHOR]

Background: Transcranial alternating current stimulation (tACS) alters cortical excitability with low-intensity alternating current and thereby modulates aberrant brain oscillations. Despite the recent increase in studies investigating the feasibility and efficacy of tACS in treating neuropsychiatric disorders, its mechanisms, as well as optimal stimulation parameters, are not fully understood. Objectives: This systematic review aimed to compile human research on tACS for neuropsychiatric disorders to delineate typical treatment parameters for these conditions and evaluate its outcomes. Methods: A search for published studies and unpublished registered clinical trials was conducted through OVID (MEDLINE, PsycINFO, and Embase), ClinicalTrials.gov, and the International Clinical Trials Registry Platform. Studies utilizing tACS to treat neuropsychiatric disorders in a clinical trial setting were included. Results: In total, 783 published studies and 373 clinical trials were screened; 53 published studies and 70 clinical trials were included. Published studies demonstrated a low risk of bias, as assessed by the Joanna Briggs Institute Critical Appraisal Tools. Neurocognitive, psychotic, and depressive disorders were the most common disorders treated with tACS. Both published studies (58.5%) and registered clinical trials (52%) most commonly utilized gamma frequency bands and tACS was typically administered at an intensity of 2 mA peak-to-peak, once daily for 20 or fewer sessions. Although the targeted brain locations and tACS montages varied across studies based on the outcome measures and specific pathophysiology of the disorders, the dorsolateral prefrontal cortex (DLPFC) was the most common target in both published studies (30.2%) and registered clinical trials (25.6%). Across studies that published results on tACS outcome measures, tACS resulted in enhanced symptoms and/or improvements in overall psychopathology for neurocognitive (all 11 studies), psychotic (11 out of 14 studies), and depressive (7 out of 8 studies) disorders. Additionally, 17 studies reported alterations in the power spectrum of the electroencephalogram around the entrained frequency band at the targeted locations following tACS. Conclusion: Behavioral and cognitive symptoms have been positively impacted by tACS. The most consistent changes were reported in cognitive symptoms following gamma-tACS over the DLPFC. However, the paucity of neuroimaging studies for each neuropsychiatric condition highlights the necessity for replication studies employing biomarker- and mechanism-centric approaches. [ABSTRACT FROM AUTHOR]

Background: Intravaginal electrical stimulation (IVES) has been explored as a potential treatment for pelvic floor disorders (PFDs), although its efficacy remains a subject of debate. We aim to conducted a comprehensive meta-analysis of relevant trials. Methods: This meta-analysis was performed under the PRISMA 2020 guideline. We meticulously searched for randomized controlled trial (RCT) studies in various databases, including PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov, spanning from inception to March 6, 2023. All studies included one treatment group of intravaginal electrical stimulation and the diseases spectrum of the studies involved different kinds of PFDs, including urinary incontinence, overactive bladder, etc. Risk of bias charts were used to assess the risk of bias in the studies and forest plots were used the demonstrate the overall effects. Results: Our analysis encompassed a total of 13 RCT studies. In most of the assessed PFD cure outcomes, the results demonstrated positive effects of IVES therapy, as indicated by the following findings: daily voiding frequency (MD = -1.57, 95% CI = -3.08 to -0.06, I² = 68%,), nocturia (MD = -1.07, 95% CI = -2.01 to -0.13,I² = 71%), Pad test, and Urinary incontinence. Nevertheless, the data concerning the impact of IVES therapy on the quality of life of individuals with PFDs did not confirm these positive results. Discussion: In light of the insufficiency in both the quality and quantity of the included studies, it is premature to draw a definitive conclusion regarding the efficacy of IVES therapy for treating PFDs. Nonetheless, our study does provide several pieces of evidence in support of the potential therapeutic effects of electrical stimulation therapy in this context. We recommend that further research in this area be conducted to provide more conclusive insights into the efficacy of IVES therapy for PFDs. [ABSTRACT FROM AUTHOR]

Electrical neurostimulation is currently used to manage epilepsy, but the most effective approach for minimizing seizure occurrence is uncertain. While functional MRI (fMRI) can reveal which brain areas are affected by stimulation, simultaneous deep brain stimulation (DBS)-fMRI examinations in patients are rare and the possibility to investigate multiple stimulation protocols is limited. In this study, we utilized the intrahippocampal kainatemousemodel ofmesial temporal lobe epilepsy (mTLE) to systematically examine the brain-wide responses to electrical stimulation using fMRI. We compared fMRI responses of saline-injected controls and epileptic mice during stimulation in the septal hippocampus (HC) at 10Hz and demonstrated the effects of different stimulation amplitudes (80-230 µA) and frequencies (1-100Hz) in epileptic mice. Motivated by recent studies exploring 1Hz stimulation to prevent epileptic seizures, we furthermore investigated the effect of prolonged 1Hz stimulation with fMRI. Compared to sham controls, epileptic mice showed less propagation to the contralateral HC, but significantly stronger responses in the ipsilateral HC and a wider spread to the entorhinal cortex and septal region. Varying the stimulation amplitude had little effect on the resulting activation patterns, whereas the stimulation frequency represented the key parameter and determined whether the induced activation remained local or spread from the hippocampal formation into cortical areas. Prolonged stimulation of epileptic mice at 1Hz caused a slight reduction in local excitability. In this way, our study contributes to a better understanding of these stimulation paradigms. [ABSTRACT FROM AUTHOR]

Introduction: The potential neuroprotective and regenerative properties of electrical stimulation (ES) were studied in rhodopsin knockout mice (Rho-/-), a murine model of inherited retinal degeneration. The study focused on assessing the impact of varying ES frequencies on visual functions and photoreceptor cell survival in Rho-/- mice. Methods: To elucidate the impact of electrical stimulation on cone survival, Rho-/- mice received either sham or transpalpebral ES using biphasic ramp or rectangular waveforms at 100 µA amplitude, starting at six weeks of age. The treatment duration spanned from one to three weeks. The optimal treatment frequency of ES sessions was determined by applying ES every one, two, or three days in three separate groups of Rho-/- mice. The sham group received daily treatments without the application of ES. Results: Our study revealed significant improvement of visual function in Rho-/- mice following daily or every-other-day noninvasive transpalpebral ES, as evidenced by electroretinogram and optomotor response-based visual behavior assays. Concurrently, assessment of outer nuclear thickness and immunohistochemistry for the cone photoreceptor cell marker PNA demonstrated pronounced increases in the survival of rods and cones and improvement in the morphology of the inner and outer segments. Discussion: This study underscores the protective effect of non-invasive ES in rhodopsin knockout-induced retinal degenerative disorders, providing a foundation for developing targeted therapeutic interventions for retinitis pigmentosa. [ABSTRACT FROM AUTHOR]

Background: Galvanic Vestibular Stimulation (GVS) is a non-invasive electrical stimulation technique that is typically used to probe the vestibular system. When using direct current or very low frequency sine, GVS causes postural sway or perception of illusory (virtual) motions. GVS is commonly delivered using two electrodes placed at the mastoids, however, placements involving additional electrodes / locations have been employed. Our objective was to systematically evaluate all known GVS electrode placements, compare induced current flow, and how it relates to the archetypal sway and virtual motions. The ultimate goal is to help users in having a better understanding of the effects of different placements. Methods: We simulated seven GVS electrode placements with same total injected current using an ultra-high resolution model. Induced electric field (EF) patterns at the cortical and the level of vestibular organs (left and right) were determined. A range of current flow metrics including potential factors such as inter-electrode separation, percentage of current entering the cranial cavity, and symmetricity were calculated. Finally, we relate current flow to reported GVS motions. Results: As expected, current flow patterns are electrode placement specific. Placements with two electrodes generally result in higher EF magnitude. Placements with four electrodes result in lower percentage of current entering the cranial cavity. Symmetric placements do not result in similar EF values in the left and the right organs respectively- highlighting inherent anatomical asymmetry of the human head. Asymmetric placements were found to induce as much as ~3-fold higher EF in one organ over the other. The percentage of current entering the cranial cavity varies between ~15% and ~40% depending on the placement. Conclusions: We expect our study to advance understanding of GVS and provide insight on probable mechanism of action of a certain electrode placement choice. The dataset generated across several metrics will support hypothesis testing relating empirical outcomes to current flow patterns. Further, the differences in current flow will guide stimulation strategy (what placement and how much scalp current to use) and facilitate a quantitatively informed rational / optimal decision. [ABSTRACT FROM AUTHOR]

Background: Cluster headache (CH) is a significant health concern due to its major socioeconomic consequences and most patients being refractory to conventional strategies. For treatment resistant CH, occipital nerve stimulation (ONS) is considered an effective treatment option. Whereas most patients do not adjust the amplitude of the ONS system, a subset changes the amplitude on a regular basis using their remote control, and are therefore referred to as 'voltage tuners'. Anxiety and self-control are thought to be central themes to this behavior. Research on this voltage tuning behavior could provide new insights in the use of ONS as acute attack treatment. To date, voltage tuning has not been assessed for CH. Hence this is a unique study aiming to investigate the occurrence and efficacy of voltage tuning in patients with CH and ONS. Methods: For this analysis, patients with CH who received ONS from 2020–2024, at our university medical center, were included. All patients underwent bilateral ONS implantation. Data on attack frequency, intensity and duration were collected retrospectively. Outcomes on the response, frequency, moment during the day, duration, rationale, sensation, average increase in amplitude, and efficacy of voltage tuning were collected with prospective interviews. Results: Thirty-three patients (M = 20) (42 ± 12.7 years) were included in the current analysis. At 1y follow-up, an overall response rate of 70% (23/33) was found for ONS. In total, 48% (18/33) of patients were defined as voltage tuners. Voltage tuning was performed with an average increase in amplitude of 92 (20–360)%, a frequency of 1–20 times/month and duration of 20 minutes-48 hours. Sensations of voltage tuning were described as "tingling" and/or "pinching". The rationale for voltage tuning in patients varied from prevention and ceasing to lowering the intensity and enhance control of CH attack. Conclusions: Outcomes show that voltage tuning may cease and/or terminate CH attacks and therefore raise interests in the use of ONS as acute attack treatment for patients with resistant CH treated with ONS. Future research on the occurrence and potential of voltage tuning will provide valuable insights for achieving optimal efficacy of ONS and quality of life in patients with CH. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation (DBS) is a potential treatment for improving movement disorder. However, few large-sample studies can reveal its efficacy and safety. This study aims to initially explore the efficacy and safety of DBS in the mesencephalic locomotor region (MLR) on motor function in patients with post-stroke hemiplegia. Methods/design: This multicenter, prospective, double-blind, randomized crossover clinical trial aims to assess the safety and effectiveness of Deep Brain Stimulation (DBS) in the mesencephalic locomotor region (MLR) for patients with moderate to severe post-stroke hemiplegia. Sixty-two patients with stable disease after a year of conservative treatment will be enrolled and implanted with deep brain electrodes. Post-surgery, patients will be randomly assigned to either the DBS group or the control group, with 31 patients in each. The DBS group will receive electrical stimulation 1 month later, while the control group will undergo sham stimulation. Stimulation will be discontinued after 3 and 6 months, followed by a 2-week washout period. Subsequently, the control group will receive electrical stimulation, while the DBS group will undergo sham stimulation. Both groups will resume electrical stimulation at the 9th and 12th-month follow-ups. Post-12-month follow-up, motor-related scores will be collected for analysis, with the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE) as the primary metric. Secondary outcomes include balance function, neuropsychiatric behavior, fall risk, daily living activities, and quality of life. This study aims to provide insights into the therapeutic benefits of DBS for post-stroke hemiplegia patients. Result/conclusion: We proposed this study for the first time to comprehensively explore the effectiveness and safety of DBS in improving motor function for post-stroke hemiplegia, and provide evidence for DBS in the treatment of post-stroke hemiplegia. Study limitations are related to the small sample size and short study period. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT05968248. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The availability of high-power lasers open new frontiers of Terahertz (THz) optics. In this paper, we present a mechanism for the enhanced THz field generation from the laser wakefield excitation during the interaction of an amplitude-modulated laser filament with a magnetized plasma. The derivation of electric and magnetic wakefields in axially magnetized plasma is obtained using the perturbative approach. Amplitude-modulated laser filament generates a significantly stronger transverse current due to laser intensity redistribution by the amplitude modulation. The modulation index of the amplitude modulated laser pulse is used to control the transverse current at THz frequency. Fourfold enhancement takes place in THz field strength for higher values of the modulation index (0–0.4). Also, the conversion efficiency of this mechanism is estimated as 1 0 − 4 that can be enhanced for higher modulation index. Scaling laws are provided for controlling and optimization of generated THz field. This work may be crucial in exploring THz optical phenomena such as THz field-induced Kerr effects and many other nonlinear effects. [ABSTRACT FROM AUTHOR]

Gel‐based adhesives show promising prospects in epidermal bioelectronics because of their potential applications in physiological signal collection and electrical stimulation. An ideal epidermal adhesive should exhibit robust adhesion for lamination and poor adhesion for easy peeling, in addition to strain‐insensitivity in electrical properties for motion‐artifact‐free physiological signal collection. Here, lignosulfonate‐derived organohydrogel adhesives with anisotropic and tunable adhesion, together with unprecedented strain‐insensitivity are synthesized. The organohydrogel exhibits a high interfacial toughness of 728 J m−2 on fresh porcine skin, while the adhesion can be screened by covering a denatured silk fibroin. An anisotropic adhesive with an adhesion heterogeneity is designed, showing a 14.2‐fold difference in adhesion strength along two different directions for on‐demand attachment and removal. The adhesive can transform into a highly porous structure, which has only a 3% resistance increase at 100% strain. The strain‐insensitivity of the adhesive lies in the strong interaction of ions and the 3D porous structure, which enables motion‐artifact‐free and high‐quality electrophysiological signal collection within the strain range of the human skin. The lignosulfonate‐derived on‐demand organohydrogel adhesive is expected to be used in epidermal bioelectronics, human‐machine interaction, metaverse, and beyond. [ABSTRACT FROM AUTHOR]

Objective: In addition to the well-established advantage that strengthened pelvic musculature increases urethral resistance in stress urinary incontinence (SUI) patients, intra-vaginal electrical stimulation (iVES) has been shown in preclinical studies to improve bladder capacity via the pudendal-hypogastric mechanism. This study investigated whether iVES also benefits bladder storage in SUI patients by focusing on compliance, a viscoelastic parameter critically defining the bladder's storage function, in a clinical study. Moreover, the potential involvement of stimulation-induced neuromodulation in iVESmodified compliance was investigated by comparing the therapeutic outcomes of SUI patients treated with iVES to those who underwent a trans-obturator tape (TOT) implantation surgery, where a mid-urethral sling was implanted without electric stimulation. Patients and methods: Urodynamic and viscoelastic data were collected from 21 SUI patients treated with a regimen combining iVES and biofeedbackassisted pelvic floor muscle training (iVES-bPFMT; 20-min iVES and 20-min bPFMT sessions, twice per week, for 3 months). This regimen complied with ethical standards. Data from 21 SUI patients who received TOT implantation were retrospectively analyzed. Mean compliance (Cm), infused volume (Vinf), and threshold pressure (Pthr) from the pressure-flow/volume investigations were assessed. Results: Compared with the pretreatment control, iVES-bPFMT consistently and significantly increased Cm (18/21; 85%, p = 0.017, N = 21) and Vinf (16/21; 76%, p = 0.046; N = 21) but decreased Pthr (16/21; 76%, p = 0.026, N = 21). In contrast, TOT implantation did not result in consistent or significant changes in Cm, Vinf, or Pthr (p = 0.744, p = 0.295, p = 0.651, respectively; all N = 21). Conclusion: Our results provide viscoelastic and thermodynamic evidence supporting an additional benefit of iVES-bPFMT to bladder storage in SUI patients by modifying bladder compliance, possibly due to the potentiated hypogastric tone, which did not occur in TOT-treated SUI patients. [ABSTRACT FROM AUTHOR]

Background: Hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis constitutes a pivotal response by surgical trauma, manifesting as a critical aspect of the acute stress reaction. This hyperactivity resulted in adverse surgical outcomes and is often associated with increased postoperative anxiety. Increased evidence suggests that Nesfatin-1 plays a crucial role in stress responses and stress-related psychiatric disorders. Electroacupuncture (EA) is widely used to alleviate stress responses and anxiety, although its mechanism of action remains unclear. This study aimed to assess the mechanisms by which hypothalamic Nesfatin-1 contribute to the alleviation of HPA axis hyperactivity and anxiety by EA. Methods: Partial hepatectomy (HT) was performed to simulate surgical trauma, and EA was applied at Zusanli (ST36) and Sanyinjiao (SP6). The levels of hypothalamic Nesfatin-1, c-Fos, and corticotropin-releasing hormone (CRH) were detected, and serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were regarded as indicators of HPA axis activity. Anxiety levels were assessed through open field tests (OFT), elevated plus maze (EPM), and light–dark box tests (LDBT). To investigate the role of Nesfatin-1, its expression was modulated using stereotactic viral injections or plasmid transfections. Transcriptome sequencing was employed to explore the downstream signaling pathways of Nesfatin-1. Additionally, brain cannula implantation was performed to facilitate targeted drug administration. Results: Our findings demonstrated that EA reduced the hypothalamic overexpression of CRH and Nesfatin-1, as well as serum levels of ACTH and CORT. Additionally, it alleviated anxiety-like behaviors resulting from surgical trauma. We observed that overexpression of Nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) triggered hyperactivity of the HPA axis and anxiety. Conversely, knocking down Nesfatin-1 in the PVN reversed these effects caused by surgical trauma. Transcriptome sequencing identified the extracellular regulated protein kinases (ERK)/cAMP-response element binding protein (CREB) pathway as a key mediator in the impacts of surgical trauma and EA on the hypothalamus. Both in vivo and in vitro studies showed that overexpression of Nesfatin-1 activated the ERK/CREB pathway. Furthermore, administering ERK or CREB inhibitors into the PVN mitigated HPA axis hyperactivity and anxiety-like behaviors induced by surgical trauma. Finally, EA was observed to decrease the phosphorylation levels of ERK and CREB in the PVN. Conclusion: EA alleviates HPA axis hyperactivity and anxiety-like behaviors caused by surgical trauma through inhibition of Nesfatin-1/ERK/CREB pathway in the hypothalamus. [ABSTRACT FROM AUTHOR]

Although stem cell therapy holds promise for the treatment of spinal cord injury (SCI), its practical applications are limited by the low degree of neural differentiation. Electrical stimulation is one of the most effective ways to promote the differentiation of stem cells into neurons, but conventional wired electrical stimulation may cause secondary injuries, inflammation, pain, and infection. Here, based on the high conductivity of graphite and the electromagnetic induction effect, graphite nanosheets with neural stem cells (NSCs) are proposed as an electromagnetic cellularized patch to generate in situ wirelessly pulsed electric signals under a rotating magnetic field for regulating neuronal differentiation of NSCs to treat SCI. The strength and frequency of the induced voltage can be controlled by adjusting the rotation speed of the magnetic field. The generated pulsed electrical signals promote the differentiation of NSCs into functional mature neurons and increase the proportion of neurons from 12.5% to 33.7%. When implanted in the subarachnoid region of the injured spinal cord, the electromagnetic cellularized patch improves the behavioral performance of the hind limbs and the repair of spinal cord tissue in SCI mice. This work opens a new avenue for remote treatment of SCI and other nervous system diseases. [ABSTRACT FROM AUTHOR]

The nociceptive withdrawal reflex (NWR) is a protective limb withdrawal response triggered by painful stimuli, used to assess spinal nociceptive excitability. Conventionally, the NWR is understood as having two reflex responses: a short-latency Aβ-mediated response, considered tactile, and a longer-latency Aδ-mediated response, considered nociceptive. However, nociceptors with conduction velocities similar to Aβ tactile afferents have been identified in human skin. In this study, we investigated the effect of a preferential conduction block of Aβ fibers on pain perception and NWR signaling evoked by intradermal electrical stimulation in healthy participants. We recorded a total of 198 NWR responses in the intact condition, and no dual reflex responses occurred within our latency bandwidth (50–150 ms). The current required to elicit the NWR was higher than the perceptual pain threshold, indicating that NWR did not occur before pain was felt. In the block condition, when the Aβ-mediated tuning fork sensation was lost while Aδ-mediated nonpainful cooling was still detectable (albeit reduced), we observed that the reflex was abolished. Further, short-latency electrical pain intensity at pre-block thresholds was greatly reduced, with any residual pain sensation having a longer latency. Although electrical pain was unaffected at suprathreshold current, the reflex could not be evoked despite a two-fold increase in the pre-block current and a five-fold increase in the pre-block pulse duration. These observations lend support to the possible involvement of Aβ-fiber inputs in pain and reflex signaling. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SCZ) is characterized by cognitive deficits that are linked to prefrontal cortex dysfunction. While transcranial direct current stimulation (tDCS) shows promise for improving cognition, the effects of intensified 3mA tDCS protocols on brain physiology are unknown. This project aims to elucidate the neurophysiological and cognitive effects of an intensified prefrontal tDCS protocol in SCZ. Methods: The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, trial. Forty-eight participants with SCZ and cognitive impairment (measured via a set of executive functions tests) will be randomly allocated to receive either a single session of active (n = 24) or sham (n = 24) tDCS (20-min, 3-mA). The anodal and cathodal electrodes are positioned over the left and right DLPFC respectively. The stimulation occurs concurrently with the working memory task, which is initiated precisely 5 minutes after the onset of tDCS. Structural and resting-state (rs-fMRI) scans are conducted immediately before and after both active and sham tDCS using a 3 Tesla scanner (Siemens Prisma model) equipped with a 64-channel head coil. The primary outcome will be changes in brain activation (measures vis BOLD response) and working memory performance (accuracy, reaction time). Discussion: The results of this study are helpful in optimizing tDCS protocols in SCZ and inform us of neurocognitive mechanisms underlying 3 mA stimulation. This study will additionally provide initial safety and efficacy data on a 3 mA tDCS protocol to support larger clinical trials. Positive results could lead to rapid and broader testing of a promising tool for debilitating symptoms that affect the majority of patients with SCZ. The results will be made available through publications in peer-reviewed journals and presentations at national and international conferences. [ABSTRACT FROM AUTHOR]

The consequences of short‐term disuse are well known, but effective countermeasures remain elusive. This study investigated the effects of neuromuscular electrical stimulation (NMES) during 5 days of bed rest on retaining lower limb muscle mass and muscle function in healthy young and old participants. One leg received NMES of the quadriceps muscle (3 × 30min/day) (NMES), and the other served as a control (CON). Isometric quadriceps strength (MVC), rate of force development (RFD), lower limb lean mass, and muscle thickness were assessed pre‐and post‐intervention. Muscle thickness remained unaltered with NMES in young and increased in old following bed rest, while it decreased in CON legs. In old participants, mid‐thigh lean mass (MTLM) was preserved with NMES while decreased in CON legs. In the young, only a tendency to change with bed rest was detected for MTLM. MVC and early‐phase RFD decreased in young and old, irrespective of NMES. In contrast, late‐phase RFD was retained in young participants with NMES, while it decreased in young CON legs, and in the old, irrespective of NMES. NMES during short‐term bed rest preserved muscle thickness but not maximal muscle strength. While young and old adults demonstrated similar adaptive responses in preventing the loss of skeletal muscle thickness, RFD was retained in the young only. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injury is a major cause of disability for which there are currently no fully effective treatments. Recent studies using epidural electrical stimulation have shown significant advances in motor rehabilitation, even when applied during chronic phases of the disease. The present study aimed to investigate the effectiveness of epidural electric stimulation in the motor recovery of rats with spinal cord injury. Furthermore, we aimed to elucidate the neurophysiological mechanisms underlying motor recovery. First, we improved upon the impact spinal cord injury model to cause severe and permanent motor deficits lasting up to 2 months. Next, we developed and tested an implantable epidural spinal cord stimulator device for rats containing an electrode and an implantable generator. Finally, we evaluated the efficacy of epidural electrical stimulation on motor recovery after spinal cord injury in Wistar rats. A total of 60 animals were divided into the following groups: (i) severe injury with epidural electrical stimulation (injury + stim, n = 15), (ii) severe injury without stimulation (group injury, n = 15), (iii) sham implantation without battery (sham, n = 15), and (iv) a control group, without surgical intervention (control, n = 15). All animals underwent weekly evaluations using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale index, inclined plane, and OpenField test starting one week before the lesion and continuing for eight weeks. After this period, the animals were sacrificed and their spinal cords were explanted and prepared for histological analysis (hematoxylin–eosin) and immunohistochemistry for NeuN, β-III-tubulin, synaptophysin, and Caspase 3. Finally, NeuN-positive neuronal nuclei were quantified through stereology; fluorescence signal intensities for β-tubulin, synaptophyin, and Caspase 3 were quantified using an epifluorescence microscope. The injury + stim group showed significant improvement on the BBB scale compared with the injured group after the 5th week (p < 0.05). Stereological analysis showed a significantly higher average count of neural cells in the injury + stim group in relation to the injury group (1783 ± 2 vs. 897 ± 3, p < 0.001). Additionally, fluorescence signal intensity for synaptophysin was significantly higher in the injury + stim group in relation to the injury group (1294 ± 46 vs. 1198 ± 23, p < 0.01); no statistically significant difference was found in β-III-tubulin signal intensity. Finally, Caspase 3 signal intensity was significantly lower in the stim group (727 ± 123) compared with the injury group (1225 ± 87 p < 0.05), approaching levels observed in the sham and control groups. Our data suggest a regenerative and protective effect of epidural electrical stimulation in rats subjected to impact-induced traumatic spinal cord injury. [ABSTRACT FROM AUTHOR]

Eccentric training induces greater hypertrophy while causing more muscle damage than concentric training. This study examined the effects of small-range eccentric contractions (SR-ECCs) and large-range eccentric contractions (LR-ECCs) on muscle morphology, contractility, and damage in rats. Thirty male Fischer 344 rats were divided into five groups: small-range ECC single-bout (SR-ECCSB, n = 4), large-range ECC single-bout (LR-ECCSB, n = 4), SR-ECC intervention (SR-ECCIntv, n = 7), LR-ECC intervention (LR-ECCIntv, n = 8), and control (Cont, n = 7). These groups underwent transcutaneous electrical stimulation involving 80 ECCs twice a week for four weeks. The results indicated that the LR-ECCSB group had more Evans blue dye-positive fibers than other groups. The SR-ECCIntv group showed no increase in the mean myofiber cross-sectional area. However, Pax7+ and Ki67+ cells significantly increased in both ECCIntv groups compared to the Cont group, and the connective tissue area was significantly greater in the LR-ECCIntv than in others. Muscle force was lower in both ECCIntv groups compared to the Cont group. These findings suggest that SR-ECC intervention may induce a smaller increase in the number of fibers with a large myofiber cross-sectional area and satellite cell proliferation with less muscle damage and myofibrosis compared to LR-ECCs. [ABSTRACT FROM AUTHOR]

The development of artificial tetrachromatic vision holds great potential to enhance human color perception and discrimination, thereby enabling more effective navigation in diverse environments. Herein, an artificial tetrachromatic synaptic device is presented built upon 2D‐3D vertically stacked semiconductors composed of tungsten diselenide (WSe2)‐gallium nitride (GaN) configuration, forming a dual‐channel floating gate transistor (FGT). Under the concerted influence of electrical and optical stimulation, the device successfully mimics fundamental tetrachromatic synaptic behaviors, including short‐term potentiation (STP), weak long‐term potentiation (wLTP), long‐term potentiation (LTP), paired‐pulse facilitation (PPF), spike number‐dependent plasticity (SNDP), and spike rate‐dependent plasticity (SRDP). Notably, the plasticity of the device can be further modulated under ultraviolet (UV) stimulation, providing insights into the modulation of synaptic plasticity through the photogenerated carrier dynamics in the GaN channel. These results imply that WSe2‐GaN‐based FGT architecture with dual‐channel characteristics seamlessly integrates optical sensing and synaptic simulation functionalities, representing a promising avenue for the development of next‐generation artificial visual perception systems (AVPS), with a particular advantage for the pursuit of high‐performance artificial tetrachromatic neuromorphic computing applications of the future. [ABSTRACT FROM AUTHOR]

[Display omitted] Severe spinal cord injury (SCI) leads to dysregulated neuroinflammation and cell apoptosis, resulting in axonal die-back and the loss of neuroelectric signal transmission. While biocompatible hydrogels are commonly used in SCI repair, they lack the capacity to support neuroelectric transmission. To overcome this limitation, we developed an injectable silk fibroin/ionic liquid (SFMA@IL) conductive hydrogel to assist neuroelectric signal transmission after SCI in this study. The hydrogel can form rapidly in situ under ultraviolet (UV) light. The mechanical supporting and neuro-regenerating properties are provided by silk fibroin (SF), while the conductive capability is provided by the designed ionic liquid (IL). SFMA@IL showed attractive features for SCI repair, such as anti-swelling, conductivity, and injectability. In vivo , SFMA@IL hydrogel used in rats with complete transection injuries was found to remodel the microenvironment, reduce inflammation, and facilitate neuro-fiber outgrowth. The hydrogel also led to a notable decrease in cell apoptosis and the achievement of scar-free wound healing, which saved 45.6 ± 10.8 % of spinal cord tissue in SFMA@IL grafting. Electrophysiological studies in rats with complete transection SCI confirmed SFMA@IL's ability to support sensory neuroelectric transmission, providing strong evidence for its signal transmission function. These findings provide new insights for the development of effective SCI treatments. [ABSTRACT FROM AUTHOR]

Angiotensin receptor blockade has been linked to aspects of aversive learning and memory formation and to the prevention of posttraumatic stress disorder symptom development. We investigated the influence of the angiotensin receptor blocker losartan on aversive Pavlovian conditioning using a probabilistic learning paradigm. In a double-blind, randomized, placebo-controlled design, we tested 45 (18 female) healthy volunteers during a baseline session, after application of losartan or placebo (drug session), and during a follow-up session. During each session, participants engaged in a task in which they had to predict the probability of an electrical stimulation on every trial while the true shock contingencies switched repeatedly between phases of high and low shock threat. Computational reinforcement learning models were used to investigate learning dynamics. Acute administration of losartan significantly reduced participants' adjustment during both low-to-high and high-to-low threat changes. This was driven by reduced aversive learning rates in the losartan group during the drug session compared with baseline. The 50-mg drug dose did not induce reduction of blood pressure or change in reaction times, ruling out a general reduction in attention and engagement. Decreased adjustment of aversive expectations was maintained at a follow-up session 24 hours later. This study shows that losartan acutely reduces Pavlovian learning in aversive environments, thereby highlighting a potential role of the renin-angiotensin system in anxiety development. [ABSTRACT FROM AUTHOR]

Purpose: Aphasia is an acquired language impairment that commonly results from stroke. Non-invasive brain stimulation (NIBS) might accelerate aphasia recovery trajectories and has seen mounting popularity in recent aphasia rehabilitation research. The present review aimed to: (1) summarise all existing literature on NIBS as a post-stroke aphasia treatment; and (2) provide recommendations for future NIBS-aphasia research. Materials and methods: Databases for published and grey literature were searched using scoping review methodology. 278 journal articles, conference abstracts/posters, and books, and 38 items of grey literature, were included for analysis. Results: Quantitative analysis revealed that ipsilesional anodal transcranial direct current stimulation and contralesional 1-Hz repetitive transcranial magnetic stimulation were the most widely used forms of NIBS, while qualitative analysis identified four key themes including: the roles of the hemispheres in aphasia recovery and their relationship with NIBS; heterogeneity of individuals but homogeneity of subpopulations; individualisation of stimulation parameters; and much remains under-explored in the NIBS-aphasia literature. Conclusions: Taken together, these results highlighted systemic challenges across the field such as small sample sizes, inter-individual variability, lack of protocol optimisation/standardisation, and inadequate focus on aphasiology. Four key recommendations are outlined herein to guide future research and refine NIBS methods for post-stroke aphasia treatment. IMPLICATIONS FOR REHABILITATION: A comprehensive review of non-invasive brain stimulation (NIBS) post-stroke aphasia literature, including all study designs, was required. Review of this literature revealed that anodal transcranial direct current stimulation is the mostly commonly used type of NIBS in aphasia treatment research. Systemic challenges across the field hinder prospective translation of NIBS into aphasia practice. Aphasia rehabilitation professionals should note that further research is required before NIBS is suitable for translation into clinical practice. [ABSTRACT FROM AUTHOR]

Bimodal neuromodulation is emerging as a nonsurgical treatment for tinnitus. Bimodal treatment combining sound therapy with electrical tongue stimulation using the Lenire device is evaluated in a controlled pivotal trial (TENT-A3, NCT05227365) consisting of 6-weeks of sound-only stimulation (Stage 1) followed by 6-weeks of bimodal treatment (Stage 2) with 112 participants serving as their own control. The primary endpoint compares the responder rate observed in Stage 2 versus Stage 1, where a responder exceeds 7 points in the Tinnitus Handicap Inventory. In participants with moderate or more severe tinnitus, there is a clinically superior performance of bimodal treatment (58.6%; 95% CI: 43.5%, 73.6%; p = 0.022) compared to sound therapy alone (43.2%; 95% CI: 29.7%, 57.8%), which is not observed in the full cohort across all severity groups. Consistent results are observed for the secondary endpoint based on the Tinnitus Functional Index (bimodal treatment: 45.5%; 95% CI: 31.7%, 59.9%; sound-only stimulation: 29.6%; 95% CI: 18.2%, 44.2%; p = 0.010), where a responder exceeds 13 points. There are no device related serious adverse events. These positive outcomes led to FDA De Novo approval of the Lenire device for tinnitus treatment. Bimodal neuromodulation combining sound therapy with electrical tongue stimulation using the Lenire device is a nonsurgical treatment for tinnitus. Here, the authors show the positive efficacy and safety results of a controlled one-arm pivotal trial that led to FDA De Novo approval of the Lenire device. [ABSTRACT FROM AUTHOR]

With electrical stimulation, retinal prostheses bypass dysfunctional photoreceptors and activate the surviving bipolar or retinal ganglion cells (RGCs). Therefore, the effective modulation of RGCs is crucial for developing retinal prostheses. Substantial research has been performed on the ability of an electrical stimulus to generate a reliable RGC response. However, different experimental conditions show varying levels of how well the electrical stimulation evokes RGC spikes. Therefore, in this study, we attempted to extract an indicator to understand how the electrical stimulation effectively evokes RGC spikes. Six cynomolgus monkeys were used: three as controls and three as an N-methyl-N-nitrosourea (MNU)-induced retinal degeneration model. The retinal recordings were performed using 8 x 8 multi-electrode arrays (MEAs). Electrical stimulation consisted of symmetrical biphasic pulses of varying amplitudes and durations. The number of stimulation conditions that resulted in significantly higher post-stimulation firing rates than pre-stimulus firing rates was defined as the modulation efficiency ratio (MER). The MER was significantly lower in degenerated retinas than in normal retinas. We investigated the relationship between the variables and the MER in normal and degenerated primate RGCs. External variables, such as duration and inter-electrode distance, and internal variables, such as average firing rates and statistics (mean, standard deviation, and coefficient of variation [CV]) of inter-spike intervals (ISIs) of spontaneous spikes, were used. External variables had similar effects on MER in normal and degenerated RGCs. In contrast, internal variables affected MER differently in normal and degenerated RGCs. While in normal RGCs, they were not related to MER, in degenerated RGCs, the mean ISIs were positively correlated with MER, and the CV of ISIs was negatively correlated with MER. The most important variable affecting MER was the mean ISI. A shorter ISI indicates hyperactive firing in the degenerated retina, which prevents electrical stimulation from evoking more RGCs. We believe that this hyperactivity in degenerated retinas results in a lower MER than that in the normal retina. Our findings can be used to optimize the selection of stimulation channels for in vitro MEA experiments and practical calibration methods to achieve higher efficiency when testing retinal prostheses. [ABSTRACT FROM AUTHOR]

Introduction: Lower leg pain and symptoms, and poor leg circulation are common in older adults. These can significantly affect their function and quality of life. Neuromuscular electrical stimulation (NMES) applied via the feet as 'foot NMES' activates the leg musculovenous pump. This study investigated the effects of foot NMES administered at home using Revitive® among community-dwelling older adults with lower leg pain and/or other lower leg symptoms such as cramps, or sensations of tired, aching, and heavy feeling legs. Methods: A randomised placebo-controlled study with three groups (2 NMES, 1 Sham) and three assessments (baseline, week 8, week 12 follow-up) was carried out. Self-reported function using Canadian occupational performance measure (COPM), leg pain, overall leg symptoms score (heaviness, tiredness, aching, or cramps), and ankle blood flow were assessed. Analysis of covariance (ANCOVA) and logistic regression were used to compare the groups. Statistical significance was set at p < 0.05 (two-sided 5%). Results: Out of 129 participants enrolled, 114 completed the study. The improvement in all outcomes were statistically significant for the NMES interventions compared to Sham at both week 8 (p < 0.01) and week 12 (p < 0.05). The improvement in COPM met the minimal clinically important difference (MCID) for the NMES interventions compared to Sham at both week 8 (p < 0.005) and week 12 (p < 0.05). Improvement in leg pain met MCID at week 8 compared to Sham (p < 0.05). Ankle blood flow increased approximately 3-fold during treatment compared to Sham. Compliance with the interventions was high and no device-related adverse events were reported. Conclusions: The home-based foot NMES is safe, and significantly improved self-reported function, leg pain and overall leg symptoms, and increased ankle blood flow compared to a Sham among older adults. Trial registration: The trial was prospectively registered in ISRCTN on 17/06/2019 with registration number ISRCTN10576209. It can be accessed at https://www.isrctn.com/ISRCTN10576209. Key points: • Eight weeks of daily home-based foot NMES therapy delivered using Revitive devices significantly improved self-reported function, leg pain and other leg symptoms in community-dwelling older adults when compared to a Sham. • Significant improvements in self-reported function and leg symptoms were sustained when measured at the follow-up four weeks after the intervention period. • During use, the foot NMES induced approximately a three-fold increase in ankle blood flow volume and intensity of blood flow when compared to a Sham. • No device-related adverse events were reported. • Compliance with the foot NMES intervention was high. [ABSTRACT FROM AUTHOR]

Theta-burst stimulation (TBS), a patterned brain stimulation technique that mimics rhythmic bursts of 3–8 Hz endogenous brain rhythms, has emerged as a promising therapeutic approach for treating a wide range of brain disorders, though the neural mechanism of TBS action remains poorly understood. We investigated the neural effects of TBS using intracranial EEG (iEEG) in 10 pre-surgical epilepsy participants undergoing intracranial monitoring. Here we show that individual bursts of direct electrical TBS at 29 frontal and temporal sites evoked strong neural responses spanning broad cortical regions. These responses exhibited dynamic local field potential voltage changes over the course of stimulation presentations, including either increasing or decreasing responses, suggestive of short-term plasticity. Stronger stimulation augmented the mean TBS response amplitude and spread with more recording sites demonstrating short-term plasticity. TBS responses were stimulation site-specific with stronger TBS responses observed in regions with strong baseline stimulation effective (cortico-cortical evoked potentials) and functional (low frequency phase locking) connectivity. Further, we could use these measures to predict stable and varying (e.g. short-term plasticity) TBS response locations. Future work may integrate pre-treatment connectivity alongside other biophysical factors to personalize stimulation parameters, thereby optimizing induction of neuroplasticity within disease-relevant brain networks. Neural mechanisms underpinning theta burst stimulation (TBS) and its implications for neuropsychiatric disorders are not fully understood. Here authors show theta burst stimulation delivered by intracranial electrodes results in measurable responses that change over time, suggestive of neuroplasticity. These responses can be predicted by baseline biophysical parameters such as functional connectivity. [ABSTRACT FROM AUTHOR]

Background: After a stroke, damage to the part of the brain that controls movement results in the loss of motor function. Brain-computer interface (BCI)-based stroke rehabilitation involves patients imagining movement without physically moving while the system measures the perceptual-motor rhythm in the motor cortex. Visual feedback through virtual reality and functional electrical stimulation is provided simultaneously. The superiority of real BCI over sham BCI in the subacute phase of stroke remains unclear. Therefore, we aim to compare the effects of real and sham BCI on motor function and brain activity among patients with subacute stroke with weak wrist extensor strength. Methods: This is a double-blinded randomized controlled trial. Patients with stroke will be categorized into real BCI and sham BCI groups. The BCI task involves wrist extension for 60 min/day, 5 times/week for 4 weeks. Twenty sessions will be conducted. The evaluation will be conducted four times, as follows: before the intervention, 2 weeks after the start of the intervention, immediately after the intervention, and 4 weeks after the intervention. The assessments include a clinical evaluation, electroencephalography, and electromyography using motor-evoked potentials. Discussion: Patients will be categorized into two groups, as follows: those who will be receiving neurofeedback and those who will not receive this feedback during the BCI rehabilitation training. We will examine the importance of motor imaging feedback, and the effect of patients' continuous participation in the training rather than their being passive. [ABSTRACT FROM AUTHOR]

Objectives: While electrical stimulation has been demonstrated to improve medical research council (MRC) scores in critically ill patients, its effectiveness remains a subject of debate. This meta-analysis aimed to discuss recent insights into the effectiveness of electrical stimulation in improving muscle strength and its effects on different clinical outcomes in critically ill adults. Methods: A comprehensive search of major electronic databases, including PubMed, Cochrane Library, and Embase, was conducted from inception to June 15, 2024, to identify randomized controlled trials (RCTs) that evaluated the effects of electrical stimulation in critically ill patients. The analysis focused on comparing electrical stimulation to standard care, sham interventions, or placebo. Outcomes of interest included MRC scores, duration of mechanical ventilation (MV), mortality rate, and intensive care unit (ICU) and hospital length of stay (LOS). Results: A total of 23 RCTs, including 1798 patients, met the inclusion criteria. The findings demonstrated a significant benefit of electrical stimulation over usual care in enhancing global muscle strength, as measured by MRC scores (MD =3.62, 95% CI 0.94 to 6.30, p = 0.0008, I2 = 87%). While subgroup analysis of electrical muscle stimulation (EMS) demonstrated no significant effect on ICU LOS, sensitivity analysis indicated a potential reduction in ICU LOS for both EMS (MD = -11.0, 95% CI -21.12 to -0.88, p = 0.03) and electrical stimulation overall (MD = -1.02, 95% CI -1.96 to -0.08, p = 0.03) compared to the control group. In addition, sensitivity analysis suggested that both electrical stimulation (MD = -2.38, 95% CI -3.81 to -0.94, p = 0.001) and neuromuscular electrical stimulation (NMES) specifically (MD = -2.36, 95% CI -3.85 to -0.88, p = 0.002) may contribute to a decrease in hospital LOS. No statistically significant differences were observed in mortality or duration of MV. Conclusion: Electrical stimulation appears to be an effective intervention for improving MRC scores in critically ill patients. However, further research is warranted to explain the potential effects of electrical stimulation on hospital LOS and ICU LOS. [ABSTRACT FROM AUTHOR]

Background: Transcranial alternating current stimulation (tACS) can apply currents of varying intensity to the scalp, modulating cortical excitability and brain activity. tACS is a relatively new neuromodulation intervention that is now widely used in clinical practice. Many papers related to tACS have been published in various journals. However, there are no articles that objectively and directly introduce the development trend and research hotspots of tACS. Therefore, the aim of this study is to use CiteSpace to visually analyze the recent tACSrelated publications, systematically and in detail summarize the current research hotspots and trends in this field, and provide valuable information for future tACS-related research. Material and methods: The database Web of Science Core Collection Science Citation Index Expanded was used and searched from build to 4 August 2023. Using the CiteSpace to analyze the authors, institutions, countries, keywords, co-cited authors, journals, and references. Results: A total of 677 papers were obtained. From 2008 to 2023, the number of publications shows an increasing trend, albeit with some fluctuations. The most productive country in this field was Germany. The institution with the highest number of publications is Carl von Ossietzky University of Oldenburg (n = 50). According to Bradford's law, 7 journals are considered core journals in the field. Herrmann, CS was the author with the most publications (n = 40), while Antal, A was the author with the highest number of co-citations (n = 391) and betweenness centrality (n = 0.16). Disease, neural mechanisms of the brain and electric stimulation are the major research areas in the field. The effect of tACS in different diseases, multi-site stimulation, combined treatment and evaluation are the future research hotspots and trends. Conclusion: tACS has research value and research potential, and more and more researchers are paying attention to it. The findings of this bibliometric study provide the current status and trends in the clinical research of tACS and may help researchers to identify hotspots s and explore new research directions in this field. [ABSTRACT FROM AUTHOR]

Functional electrical stimulation (FES) can support functional restoration of a paretic limb post-stroke. Hebbian plasticity depends on temporally coinciding pre- and post-synaptic activity. A tight temporal relationship between motor cortical (MC) activity associated with attempted movement and FES-generated visuo-proprioceptive feedback is hypothesized to enhance motor recovery. Using a brain–computer interface (BCI) to classify MC spectral power in electroencephalographic (EEG) signals to trigger FES-delivery with detection of movement attempts improved motor outcomes in chronic stroke patients. We hypothesized that heightened neural plasticity earlier post-stroke would further enhance corticomuscular functional connectivity and motor recovery. We compared subcortical non-dominant hemisphere stroke patients in BCI-FES and Random-FES (FES temporally independent of MC movement attempt detection) groups. The primary outcome measure was the Fugl-Meyer Assessment, Upper Extremity (FMA-UE). We recorded high-density EEG and transcranial magnetic stimulation-induced motor evoked potentials before and after treatment. The BCI group showed greater: FMA-UE improvement; motor evoked potential amplitude; beta oscillatory power and long-range temporal correlation reduction over contralateral MC; and corticomuscular coherence with contralateral MC. These changes are consistent with enhanced post-stroke motor improvement when movement is synchronized with MC activity reflecting attempted movement. [ABSTRACT FROM AUTHOR]

Background: Central neuropathic pain after foramen magnum decompression (FMD) for Chiari malformation type 1 (CM-1) with syringomyelia can be residual and refractory. Here we present a case of refractory central neuropathic pain after FMD in a CM-1 patient with syringomyelia who achieved improvements in pain following spinal cord stimulation (SCS) using fast-acting sub-perception therapy (FAST™). Case presentation: A 76-year-old woman presented with a history of several years of bilateral upper extremity and chest-back pain. CM-1 and syringomyelia were diagnosed. The pain proved drug resistant, so FMD was performed for pain relief. After FMD, magnetic resonance imaging showed shrinkage of the syrinx. Pain was relieved, but bilateral finger, upper arm and thoracic back pain flared-up 10 months later. Due to pharmacotherapy resistance, SCS was planned for the purpose of improving pain. A percutaneous trial of SCS showed no improvement of pain with conventional SCS alone or in combination with Contour™, but the combination of FAST™ and Contour™ did improve pain. Three years after FMD, percutaneous leads and an implantable pulse generator were implanted. The program was set to FAST™ and Contour™. After implantation, pain as assessed using the McGill Pain Questionnaire and visual analog scale was relieved even after reducing dosages of analgesic. No adverse events were encountered. Conclusion: Percutaneously implanted SCS using FAST™ may be effective for refractory pain after FMD for CM-1 with syringomyelia. [ABSTRACT FROM AUTHOR]

• Afferent stimulation elicited a greater corticospinal drive to lumbar multifidus muscles in CLBP in comparison to controls. • Afferent stimulation alone elicited a larger reduction in paravertebral muscles activity compared to controls. • These results suggest an alteration of sensorimotor integration in our sample of participants with chronic low back pain. Objective: Chronic low back pain (CLBP) impacts on spine movement. Altered sensorimotor integration can be involved. Afferents from the lumbo-pelvic area might be processed differently in CLBP and impact on descending motor control. This study aimed to determine whether afferents influence the corticomotor control of paravertebral muscles in CLBP. Fourteen individuals with CLBP (11 females) and 13 pain-free controls (8 females) were tested with transcranial magnetic stimulation (TMS) to measure the motor-evoked potential [MEP] amplitude of paravertebral muscles. Noxious and non-noxious electrical stimulation, and magnetic stimulation in the lumbo-sacral area were used as afferent stimuli and triggered 20 to 200 ms prior to TMS. EMG modulation elicited by afferent stimulation alone was measured to control net motoneuron excitability. MEP/EMG ratio was used as a measure of corticospinal excitability with control of net motoneuron excitability. MEP/EMG ratio was larger at 60, 80 and 100-ms intervals in CLBP compared to controls, and afferent stimulations alone reduced EMG amplitude greater in CLBP than controls at 100 ms. Our results suggest alteration in sensorimotor integration in CLBP highlighted by a greater facilitation of the descending corticospinal input to paravertebral muscles. Our results can help to optimise interventions by better targeting mechanisms. [ABSTRACT FROM AUTHOR]

For the human brain to operate, populations of neurons across anatomical structures must coordinate their activity within milliseconds. To date, our understanding of such interactions has remained limited. We recorded directly from the hippocampus (HPC), posteromedial cortex (PMC), ventromedial/orbital prefrontal cortex (OFC), and the anterior nuclei of the thalamus (ANT) during two experiments of autobiographical memory processing that are known from decades of neuroimaging work to coactivate these regions. In 31 patients implanted with intracranial electrodes, we found that the presentation of memory retrieval cues elicited a significant increase of low frequency (LF < 6 Hz) activity followed by cross-regional phase coherence of this LF activity before select populations of neurons within each of the four regions increased high-frequency (HF > 70 Hz) activity. The power of HF activity was modulated by memory content, and its onset followed a specific temporal order of ANT→HPC/PMC→OFC. Further, we probed cross-regional causal effective interactions with repeated electrical pulses and found that HPC stimulations cause the greatest increase in LF-phase coherence across all regions, whereas the stimulation of any region caused the greatest LF-phase coherence between that particular region and ANT. These observations support the role of the ANT in gating, and the HPC in synchronizing, the activity of cortical midline structures when humans retrieve self-relevant memories of their past. Our findings offer a fresh perspective, with high temporal fidelity, about the dynamic signaling and underlying causal connections among distant regions when the brain is actively involved in retrieving self-referential memories from the past. [ABSTRACT FROM AUTHOR]

Neurofibromatosis Type 1 (NF1) is a complex genetic disorder characterized by the development of benign neurofibromas, which can cause significant morbidity in affected individuals. While the molecular mechanisms underlying NF1 pathogenesis have been extensively studied, the development of effective therapeutic strategies remains a challenge. This paper presents the development and validation of a novel biomaterial testing model to enhance our understanding of NF1 pathophysiology, disease mechanisms and evaluate potential therapeutic interventions. Our long-term goal is to develop an invitro model of NF1 to evaluate drug targets. We have developed an in vitro system to test the cellular behavior of NF1 patient derived cells on electroconductive aligned nanofibrous biomaterials with electrical stimulatory cues. We hypothesized that cells cultured on electroconductive biomaterial will undergo morphological changes and variations in cell proliferation that could be further enhanced with the combination of exogenous electrical stimulation (ES). In this study, we developed electrospun Hyaluronic Acid–Carbon Nanotube (HA-CNT) nanofiber scaffolds to mimic the axon's topographical and bioelectrical cues that influence neurofibroma growth and development. The cellular behavior was qualitatively and quantitively analyzed through immunofluorescent stains, Alamar blue assays and ELISA assays. Schwann cells from NF1 patients appear to have lost their ability to respond to electrical stimulation in the development and regeneration range, which was seen through changes in morphology, proliferation and NGF release. Without stimulation, the conductive material enhances NF1 SC behavior. Wild-type SC respond to electrical stimulation with increased cell proliferation and NGF release. Using this system, we can better understand the interaction between axons and SC that lead to tumor formation, homeostasis and regeneration. [ABSTRACT FROM AUTHOR]