Search

Background: Gastrocutaneous fistula is a rare complication following Roux-en-Y gastric bypass, a commonly performed bariatric surgery. While most ECFs respond to conservative management, some do not close despite adequate nutritional support, infection source control, and drainage management. As such, the chronicity of these difficult-to-treat wounds can be physically and economically costly to patients., Case Report: A 53-year-old female with a history of Roux-en-Y gastric bypass developed a gastrocutaneous fistula secondary to a perforated gastrojejunal ulcer, requiring immediate surgical intervention. After being discharged from the hospital, 37 days of conservative management and NPWT did not reduce the size of the fistula tract. To help control the patient's chronic abdominal pain and increase the rate of wound healing, the patient underwent treatment with HFES (20 kHz) delivered using a handheld transcutaneous electrical nerve stimulator. This electrotherapy was found to reduce the majority of the patient's pain within the first treatment session. The patient's fistula also began to decrease in size within 1 week of initiating treatment., Conclusion: This case report details the successful closure of a gastrocutaneous fistula after administration of HFES 3 times a week over the course of 25 days. The mechanism of action of HFES and its role in the wound healing process are also discussed.

The aim of this study was to investigate the clinical efficacy of combining pelvic floor neuromuscular stimulation treatment (NMES) with sodium hyaluronate in preventing intrauterine adhesions (IUA) following abortion. A total of 140 women who underwent artificial abortion were enrolled. The control group received only an intrauterine injection of sodium hyaluronate post-surgery, while the observation group received both the injection and daily pelvic floor NMES treatments, beginning on the day after the abortion. Monthly follow-ups on menstrual conditions were conducted for six months post-surgery. Fasting venous blood samples from both groups were collected on the second day post-abortion and the day after treatment. Transvaginal color Doppler ultrasound was used on the second day post-abortion and the 15th day post the first menstrual cycle to measure endometrial thickness, and the pulsatility and resistance indices of the endometrial spiral arteries. Over the six-month follow-up, the combination therapy group exhibited a notably lower IUA incidence compared to the control group (2.8% vs. 15.7%). Furthermore, combined treatment significantly expedited post-abortion menstrual recovery, reduced vaginal bleeding volume and duration (P < 0.001). It also increased endometrial thickness and reduced the endometrial spiral artery's pulsatility and resistance indices (P < 0.05). In addition, lower serum tumor necrosis factor alpha (TNF-α) and higher interleukin-10 (IL-10) were found in the observation group compared to the control group (P < 0.05). The combination therapy offers significant advantages in preventing and reducing IUA after abortion, resulting in a substantial reduction in IUA occurrence.

Purpose: Medialization procedures for unilateral vocal fold (VF) paralysis generally improve voice but do not fully replace dynamic VF adduction. Paralyzed VFs typically experience synkinetic reinnervation, which makes it feasible to elicit movement through electrical stimulation. We tested a novel laryngeal pacing implant capable of providing closed-loop (automatic) stimulation of a VF triggered by electromyography (EMG) potentials from the contralateral VF., Method: A custom, battery-powered, microprocessor-based stimulator was tested in eight dogs with bipolar electrodes implanted for recording EMG from the left VF and stimulating adduction of the right VF. A cuff electrode on the left recurrent laryngeal nerve (RLN) stimulated unilateral VF adduction, modeling voluntary control in anesthetized animals. Closed-loop stimulation was tested in both acute and chronic experiments. Synkinetic reinnervation was created in two animals by right RLN transection and suture repair to model unilateral VF paralysis., Results: In all animals, left VF activation through RLN stimulation generated a robust EMG response that rapidly triggered stimulation of contralateral thyroarytenoid and lateral cricoarytenoid muscles, causing nearly simultaneous bilateral adduction. Optimal triggering of VF stimulation from elicited EMG was achieved using independent onset and offset thresholds. Real-time artifact blanking allowed closed-loop stimulation without self-perpetuating feedback, despite the proximity of recording and stimulation electrodes., Conclusions: Using a custom implant system, we demonstrated real-time closed-loop stimulation of one VF triggered by the activation of the contralateral VF. This approach could potentially restore dynamic glottic closure for reflexive behaviors or phonation in cases of unilateral VF paralysis with synkinetic reinnervation., Supplemental Material: https://doi.org/10.23641/asha.24492133.

Objective: The N13 component of somatosensory evoked potential (N13 SEP) represents the segmental response of cervical dorsal horn neurons. Neurophysiological studies in healthy participants showed that capsaicin-induced central sensitization causes an increase of the N13 SEP amplitude. Consequently, in human research, this spinal component may serve as a valuable readout of central sensitization. In this study, we wanted to verify if the sensitivity of the N13 SEP for detecting central sensitization is consistent across different experimental pain models inducing central sensitization and secondary hyperalgesia, namely high and low-frequency electrical stimulation (HFS and LFS)., Methods: In 18 healthy participants, we recorded SEP after bilateral ulnar nerve stimulation before and after secondary hyperalgesia was induced through HFS and LFS applied on the ulnar nerve territory of the hand of one side. The area of secondary hyperalgesia was mapped with a calibrated 128-mN pinprick probe, and the mechanical pain sensitivity with three calibrated 16-64-256-mN pinprick probes., Results: Although both HFS and LFS successfully induced secondary hyperalgesia only LFS increased the amplitude of the N13 SEP., Conclusions: These findings suggest that the sensitivity of the N13 SEP for detecting dorsal horn excitability changes may critically depend on the different experimental pain models., Significance: Our results indicate that LFS and HFS could trigger central sensitization at the dorsal horn level through distinct mechanisms, however this still needs confirmation by replication studies., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Ventilator-induced diaphragm dysfunction (VIDD), a dysfunction of the diaphragm muscle caused by prolonged mechanical ventilation (MV), is an important factor that hinders successful weaning from ventilation. We evaluated the effects of electrical stimulation of the diaphragm muscle (pulsed current with off-time intervals) on genetic changes during 12 h of MV (E-V12). Rats were divided into four groups: control, 12-h MV, sham operation, and E-V12 groups. Transcriptome analysis using an RNA microarray revealed that 12-h MV caused upregulation of genes promoting muscle atrophy and downregulation of genes facilitating muscle synthesis, suggesting that 12-h MV is a reasonable method for establishing a VIDD rat model. Of the genes upregulated by 12-h MV, 18 genes were not affected by the sham operation but were downregulated by E-V12. These included genes related to catabolic processes, inflammatory cytokines, and skeletal muscle homeostasis. Of the genes downregulated by 12-h MV, 6 genes were not affected by the sham operation but were upregulated by E-V12. These included genes related to oxygen transport and mitochondrial respiration. These results suggested that 12-h MV shifted gene expression in the diaphragm muscle toward muscle degradation and that electrical stimulation counteracted this shift by suppressing catabolic processes and increasing mitochondrial respiration., (© 2023. The Author(s).)

Background: Gastric electrical stimulation (GES) is an effective therapy in medically refractory chronic nausea and vomiting. GES is assumed to be a contraindication for pregnancy. We examined the safety of GES during pregnancy and its clinical impact on vomiting symptoms., Methods: A retrospective study was performed in two tertiary centers including all female patients of childbearing age implanted with GES. Patients without pregnancy while on GES were asked about their desire and concerns about pregnancy. Patients who were pregnant while on GES therapy were interviewed about the course of the pregnancy and labor, as well as the health of the children., Key Results: Among 91 patients implanted at childbearing age, 54 patients without pregnancy answered the questionnaire. Nine patients (16.7%) reported a desire for pregnancy and five patients (7.4%) reported worries about the safety of GES during pregnancy. Sixteen pregnancies were reported in 10 patients. All pregnancies ended in a live birth with premature birth in 12 pregnancies (75.0%). No health concern was currently noted in these children. No severe GES-related complications occurred during pregnancy with only pain at the implantation site reported during 3 pregnancies (18.8%). The severity and frequency of nausea and vomiting significantly increased during the first trimester (p = 0.04 and p = 0.005, respectively) and decreased after the delivery, becoming lower than before the pregnancy (p = 0.044 and p = 0.011, respectively)., Conclusion & Inferences: Patients are concerned regarding pregnancy while being treated with GES. No serious maternal or fetal complications related to GES were noted in our cohort., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Purpose: To compare fixed transverse textile electrodes (TTE) knitted into a sock versus motor point placed standard gel electrodes (MPE) on peak venous velocity (PVV) and discomfort, during calf neuromuscular electrical stimulation (calf-NMES)., Methods: Ten healthy participants received calf-NMES with increasing intensity until plantar flexion (measurement level I = ML I), and an additional mean 4 mA intensity (ML II), utilizing TTE and MPE. PVV was measured with Doppler ultrasound in the popliteal and femoral veins at baseline, ML I and II. Discomfort was assessed with a numerical rating scale (NRS, 0-10). Significance was set to p < 0.05., Results: TTE and MPE both induced significant increases in PVV from baseline to ML I and significantly higher increases to ML II, in both the popliteal and femoral veins (all p < 0.001). The popliteal increases of PVV from baseline to both ML I and II were significantly higher with TTE versus MPE (p < 0.05). The femoral increases of PVV from baseline to both ML I and II were not significantly different between TTE and MPE. TTE versus MPE resulted at ML I in higher mA and NRS (p < 0.001), and at ML II in higher mA (p = 0.005) while NRS was not significantly different., Conclusion: TTE integrated in a sock produces intensity-dependent increases of popliteal and femoral hemodynamics comparable to MPE, but results in more discomfort at plantar flexion due to higher current required. TTE exhibits in the popliteal vein higher increases of PVV compared to MPE., Trial Registration: Trial&#95;ID: ISRCTN49260430. Date: 11/01/2022. Retrospectively registered., (© 2023. The Author(s).)

Olfactory disorders may be temporary or permanent and can have various causes. Currently, many COVID-19 patients report a reduced or complete loss of olfactory function. A wide range of treatment options have been investigated in the past, such as olfactory training, acupuncture, medical therapy, transcranial magnetic stimulation, or surgical excision of olfactory epithelium, e.g., in severe qualitative smell disorders. The development of a bioelectric nose, e.g., in connection with direct electrical stimulation or transplantation of olfactory epithelium or stem cells, represent treatment options of the future. The basis of these developments and the state of knowledge is discussed in the following work., (© 2023. The Author(s).)

Dysphagia is a serious cause of morbidity and mortality in stroke survivors. Electrical stimulation is often included as part of the treatment plan for dysphagia and can be applied at a sensory or motor level intensity. However, evidence to support these different modes of stimulation is lacking. This study compared the effectiveness of sensory and motor level stimulation on post-stroke dysphagia. This is a randomized trial conducted in an inpatient rehabilitation facility. Thirty-one participants who had dysphagia caused by stroke within 6 months prior to enrolment were included. Participants were excluded if they had a contraindication for electrical stimulation, previous stroke, psychiatric disorder, contraindications for modified barium swallow study (MBSS), or pre-morbid dysphagia. Each patient received ten sessions that included 45 min of anterior neck sensory or motor level electrical stimulation in addition to traditional dysphagia therapy. Motor stimulation was administered at an intensity sufficient to produce muscle contractions. Sensory stimulation was defined as the threshold at which the patient feels a tingling sensation on their skin. Swallow functional assessment measure (FAM), dysphagia outcome severity scale (DOSS), national outcome measurement system (NOMS), penetration aspiration scale (PAS), diet change, and the swallowing quality of life questionnaire (SWAL-QOL). Clinical outcomes were analyzed using a Wilcoxon signed-rank test, Mann-Whitney U test, RM ANOVA, or chi-square analysis. There was no significant difference in age, length of stay, or initial swallow FAM between groups. Patients in the sensory group showed significant improvement on swallow FAM, DOSS, and NOMS, while those in the motor group did not (Sensory: Swallow FAM (S = 48, p = 0.01), DOSS (S = 49.5, p = 0.001), NOMS (S = 52.5, p = 0.006); Motor: Swallow FAM (S = 20.5, p = 0.2), DOSS (S = 21, p = 0.05), NOMS (S = 29.5, p = 0.2)). When the groups were combined, there was statistically significant improvement on all measures except the PAS (Swallow FAM (S = 138.5, p = 0.003), DOSS (S = 134.5, p < 0.001), NOMS (S = 164, p = 0.0004)). When comparing motor to sensory NMES, there was no significant difference between groups for Swallow FAM (p = .12), DOSS (p = 0.52), or NOMS (p = 0.41). There was no significant difference in diet change for solid food or liquids among the groups, although 50% more participants in the sensory group saw improvement in diet. This study supports the use of electrical stimulation as part of the treatment plan for post-stroke dysphagia. Sensory-level stimulation was associated with greater improvement on outcome measures compared to motor level stimulation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Osteoporosis is mainly a geriatric disease with a high incidence, and the resulting spinal fractures and hip fractures cause great harm to patients. Anti-osteoporosis drugs are the main treatment for osteoporosis currently, but these drugs have potential clinical limitations and side effects, so the development of new therapies is of great significance to patients with osteoporosis. Electrical stimulation therapy mainly includes pulsed electromagnetic fields (PEMF), direct current (DC), and capacitive coupling (CC). Meanwhile, electrical stimulation therapy is clinically convenient without side effects. In recent years, many researchers have explored the use of electrical stimulation therapy for osteoporosis. Based on this, the role of electrical stimulation therapy in osteoporosis was summarized. In the future, electrical stimulation might become a new treatment for osteoporosis.

Electrical stimulation (ES) is effective for disuse-induced muscle atrophy. However, the acute effect of ES on muscle protein synthesis (MPS) and muscle protein breakdown (MPB) remains unclear. We investigated the effect of a single-session ES treatment on mTORC1 signaling, MPS, and MPB in the soleus muscle of 2-week hindlimb unloaded rats. Sprague Dawley rats (n = 12 male) were randomly divided into control (CON) and hindlimb unloaded (HU) groups. After 2 weeks, the right soleus muscle was percutaneously stimulated and underwent supramaximal isometric contractions. The left soleus muscle served as an internal control. We collected soleus muscle samples 6 h after ES. Two weeks of HU decreased p70S6K and S6rp activation, downstream factors for mTORC1 signaling, and SUnSET method-assessed MPS, but increased the LC3-II/I ratio, an indicator of autophagy. ES on disused muscle successfully activated mTORC1 signaling but did not affect MPS. Contrary, ES decreased ubiquitinated proteins expression and LC3B-II/I ratio. HU might affect mTORC1 activation and MPS differently in response to acute ES possibly due to excessive ROS production caused by ES. Our findings suggest that ES applied to disused skeletal muscles may suppress MPB, but its effect on MPS appears to be attenuated.

Introduction: Dysphagia as a consequence of multiple sclerosis (MS) puts individuals at higher risk of dehydration, malnutrition, and aspiration pneumonia. This study intended to investigate the effects of a combined program of neuromuscular electrical stimulation (NMES) and conventional swallowing therapy to improve swallow safety and efficiency, oral intake, and physical, emotional, and functional impacts of dysphagia in people with dysphagia and MS., Methods: In this single-case experimental study with ABA design, two participants with dysphagia caused by MS underwent 12 sessions therapy during 6 weeks following a baseline of 4 evaluation sessions. They were evaluated 4 more times in the follow-up phase after therapy sessions. Scores of Mann Assessment of Swallowing Ability (MASA), DYsphagia in MUltiple Sclerosis (DYMUS), and timed test of swallowing capacity were obtained at baseline, during treatment, and in the follow-up phases. The Dysphagia Outcome and Severity Scale (DOSS) based on videofluoroscopic swallow studies, Persian-Dysphagia Handicap Index (Persian-DHI), and Functional Oral Intake Scale (FOIS) were also completed before and after treatment. Visual analysis and percentage of nonoverlapping data were calculated., Results: MASA, DYMUS, FOIS, and DHI scores indicated significant improvement in both participants. Although the scores of the timed test of swallowing capacity in participant 1 (B.N.) and DOSS in participant 2 (M.A.) showed no changes, considerable improvements including reducing the amount of residue and the number of swallows required to clear bolus were seen in the posttreatment videofluoroscopic records of both participants., Conclusion: NMES in conjunction with conventional dysphagia therapy based on motor learning principles could improve the swallowing function and decrease disabling effects of dysphagia on different aspects of life in participants with dysphagia caused by MS., (© 2023 S. Karger AG, Basel.)

Background: Ventricular arrhythmia inducibility is one of the ideal endpoints of ventricular tachycardia (VT) ablation. However, it may be challenging to implement programmed electrical stimulation (PES) at the end of the procedure under several circumstances. The long-term outcome of patients who did not undergo PES after VT ablation remains largely unknown., Purpose: To investigate the details and long-term outcome of VT ablation in patients who did not undergo PES at the end of the ablation procedure., Methods: Among 183 VT ablation procedures in patients with structural heart disease who underwent VT ablation using an irrigated catheter, we enrolled those who did not undergo PES after VT ablation. VT ablation strategy involved targeting clinical VT plus pacemap-guided substrate ablation if inducible. When VT was not inducible, substrate-based ablation was performed. The primary endpoint was VT recurrence., Results: In 58 procedures, post-ablation VT inducibility was not assessed. The causes were non-inducibility of sustained VT before ablation (27/58, 46.6%), long procedure time (27.6%, mean 392 min), complications (10.3%), intolerant hemodynamic state (10.3%), and inaccessible or unsafe target (6.9%). With regard to the primary endpoint, 23 recurrences (39.7%) were observed during a mean follow-up period of 2.5 years. Patients with non-inducibility before ablation showed less VT recurrences (4/27, 14.8%) during follow-up than patients with other causes of untested PES after ablation (19/31, 61.2%) (Log-rank < 0.001)., Conclusions: VT recurrence was not observed in approximately 60% of the patients who did not undergo PES at the end of the ablation procedure. PES after VT ablation may be not needed among patients with pre-ablation non-inducibility., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

It is unknown whether watching other people in high pain increases mechanical hypersensitivity induced by pain. We applied high-frequency electrical stimulation (HFS) on the skin of healthy volunteers to induce pinprick mechanical hypersensitivity. Before HFS participants were randomly allocated to 2 groups: in the low pain group, which was the control condition, they watched a model expressing and reporting lower pain scores, in the high pain group the model expressed and reported higher scores. The 2 videos were selected on the basis of a pilot/observational study that had been conducted before. We tested the differences in perceived intensity of the HFS procedure, in the development of hypersensitivity and the role of fear and empathy. The high pain group reported on average higher pain ratings during HFS. The perceived intensity of hypersensitivity, but not the unpleasantness or the length of the area was higher in the high pain group. Our results suggest that watching a person expressing more pain during HFS increases one's own pain ratings during HFS and may weakly facilitate the development of secondary mechanical hypersensitivity, although this latter result needs replication. PERSPECTIVE: Observing a person in high pain can influence the perceived pain intensity of a procedure leading to secondary mechanical hypersensitivity, and has a weak effect on hypersensitivity itself. The role of fear remains to be elucidated., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Galvanic vestibular stimulation has been evaluated in the context of vestibular rehabilitation. The objective was to identify evidence in the scientific literature about the clinical applications of galvanic vestibular stimulation., Methods: In this systematic review, the articles describing the applications of galvanic vestibular stimulation were extracted from PubMed, Web of Science, MEDLINE, Scopus, LILACS and SciELO databases. The survey was limited to articles published in English, Portuguese and Spanish. All the articles about the clinical applications of galvanic vestibular stimulation were compiled. Repeated articles in the databases, literature review articles, case reports, letters and editorials were excluded. The descriptors included: galvanic vestibular stimulation, postural balance, central nervous system diseases, vestibular diseases, spinal cord diseases and cognition., Results: The search strategy resulted in the initial selection of 994 articles; the reading of titles and abstracts was accomplished in 470 articles and the complete reading in 23 articles. Clinical applications of galvanic vestibular stimulation included Ménière's disease, vestibular neuritis, bilateral vestibular disorders, vestibular schwannoma, Parkinson's disease, ischemic central lesions, motor myelopathies, anxiety disorders, cognition and memory., Conclusion: Galvanic vestibular stimulation has been considered a potentially useful strategy for balance rehabilitation, since it has the effect of stimulating the central connections related to the postural balance, favoring new neuronal synapses that allow the partial or total recovery of postural imbalance., (Copyright © 2022 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: Critical Illness Neuromyopathy (CIPNM) is a complication in sepsis patients with still enigmatic disease mechanisms. We investigated a novel electrical stimulation method to better define neuromuscular dysfunction in patients with CIPNM., Methods: We studied 18 sepsis CIPNM patients on intensive care units, 13 at an early and 5 at a later disease stage, 7 sepsis control, and 8 neuropathy control patients. We applied slow conditioning electrical pulses at motor nerves and directly at the muscle to investigate a facilitation phenomenon (FP) of small or absent compound motor action potentials (CMAPs)., Results: Serial pulses induced a 2 to 490-fold increase in CMAP amplitudes in 17/18 Intensive Care Unit (ICU)-CIPNM patients (p < 0.001). These effects were short lived and reproducible. Direct muscle stimulation in the tibialis anterior muscle resulted in up to 130-fold FP in 7/9 patients tested (p < 0.01). In 4/5 post-ICU CIPNM patients FP was up to 10-fold. None of the 7 ICU sepsis control patients without CIPNM with similar disease severity and none of 8 neuropathy patients showed FP (p < 0.001). On needle EMG only 5/16 ICU patients tested revealed spontaneous activity., Conclusions: Conditioning electrical stimulation detected a functional component of the disease process showing temporary improvement in sepsis-associated CIPNM., Significance: New test differentiates functional from degenerative pathology., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to review systematically the literature and to investigate the effects of electrical stimulation in treating dysphonia., Study Design: This is a systematic review., Methods: The publications indexed on the MEDLINE, LILACS, PubMed, Web of Science, and SciELO databases were searched. Original articles with experimental, clinical trial and randomized studies involving a control group and approaching dysphonia treatment with electrical stimulation in humans, regardless of age, gender, or race were included. Those excluded were theses, editorials, comments and opinions, reflexive articles, case studies, experimental studies with animals, models, projects, reports and technical reports, and review articles, as well as articles approaching other alterations, not related to dysphonia., Results: Eleven articles were found and it evaluated the effects of neuromuscular electrical stimulation (NMES) and transcutaneous electrical nerve stimulation on dysphonia caused by vocal fold paralysis, spasmodic dysphonia, behavioral dysphonia, and in patients with vocal fold nodules. The methodological analysis of the articles through the PEDro scale resulted in a mean score of 5.18; the studies were classified as either high quality (N = 3) or fair quality (N = 8). The results indicated that electrical stimulation had a therapeutic effect on various aspects of dysphonia. However, due to the high risk of bias and the heterogeneity of the studies, it is not possible to state the effectiveness of electrical stimulation in treating dysphonia., Conclusion: Using electrical stimulation as an evidence-based conventional rehabilitation therapy in the treatment of dysphonia cannot yet be done., (Copyright © 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Mouse models of genetic and acquired risk factors for atrial fibrillation (AF) have proven valuable in investigating the molecular determinants of AF. Programmed electrical stimulation can be performed using transesophageal atrial pacing as a survival procedure, thus enabling serial testing in the same animal. However, numerous pacing protocols exist, which complicates the reproducibility. The present protocol aims to provide a standardized strategy to develop model-specific experimental parameters to improve reproducibility between studies. Preliminary studies are performed to optimize the experimental methods for the specific model under investigation, including age at the time of the study, sex, and parameters of the pacing protocol (e.g., mode of pacing and definition of AF susceptibility). Importantly, care is taken to avoid high stimulus energies, as this can cause stimulation of the ganglionic plexi with inadvertent parasympathetic activation, manifested by exaggerated atrioventricular (AV) block during pacing and often associated with artifactual AF induction. Animals demonstrating this complication must be excluded from the analysis.

Background: Stroke is the main cause of oropharyngeal neurogenic dysphagia. Electrostimulation has been used as a therapeutic tool in these cases. However, there are few studies that prove its effectiveness. We evaluated the effect of functional electrostimulation as a complement to conventional speech therapy in patients with dysphagia after a stroke in a stroke unit., Methods: We performed a clinical, randomized, and controlled trial divided into intervention group (IG) (n = 16) and control group (CG) (n = 17). All patients were treated with conventional speech therapy, and the IG also was submitted to the functional electrotherapy. Primary outcomes were Functional Oral Ingestion Scale (FOIS) and Swallowing videoendoscopy (FEES). The degree of dysphagia was scored in functional, mild, moderate and severe dysphagia according to FEES procedure. Dysphagia Risk Evaluation Protocol (DREP) was considered a secondary outcome., Results: There was a significant difference regarding FOIS scores after 5 days of intervention in groups. Both groups also showed a tendency to improve dysphagia levels measured by FEES, although not statistically significant. Improvements on oral feeding was seen in both groups. No significant differences between groups before and after the intervention were detected by DREP scores. Electrical stimulation did not show additional benefits beyond conventional therapy when comparing outcomes between groups., Conclusion: Conventional speech therapy improved oral ingestion even regardless the use of electrostimulation in a stroke unit., Trial Registration: This research was registered in ClinicalTrials.gov (Identifier: NCT03649295 ) in 28/08/2018 and in the Brazilian Registry of Clinical Trials (ReBEC) (Register Number: RBR-56QK5J), approval date: 18/12/2018. HGF Ethics Committee Approval Number: N. 2.388.931., (© 2022. The Author(s).)

Background: Neuromuscular electrical stimulation (NMES) has been used as a treatment option in the therapy of dysphagia for several years. In a previous review of the literature, it was concluded that NMES might be a valuable adjunct in patients with dysphagia and in patients with vocal fold paresis. However, due to different stimulation protocols, electrode positioning and various underlying pathological conditions, it was difficult to compare the studies which were identified and it was concluded that more empirical data is needed to fully understand the benefits provided by NMES. The purpose of this systematic review is, therefore, to evaluate recent studies regarding a potential effectiveness of transcutaneous NMES applied to the anterior neck as a treatment for dysphagia considering these different aspects., Method: For this systematic review, a selective literature research in PubMed has been carried out on 5 th May 2021 using the terms electrical stimulation AND dysphagia and screened for inclusion criteria by two reviewers in Rayyan. The search resulted in 62 hits., Results: Studies were excluded due to their publication language; because they did not meet inclusion criteria; because the topical focus was a different one; or because they did not qualify as level 2 studies. Eighteen studies were identified with varying patient groups, stimulation protocols, electrode placement and therapy settings. However, 16 studies have reported of beneficial outcomes in relation with NMES., Discussion: The purpose of this systematic review was to evaluate the most recent studies regarding a potential effectiveness of NMES as a treatment for oropharyngeal dysphagia considering different aspects. It could generally be concluded that there is a considerable amount of level 2 studies which suggest that NMES is an effective treatment option, especially when combined with TDT for patients with dysphagia after stroke and patients with Parkinson's disease, or with different kinds of brain injuries. Further research is still necessary in order to clarify which stimulation protocols, parameters and therapy settings are most beneficial for certain patient groups and degrees of impairment., Competing Interests: The authors work on a project concerning electrical stimulation and dysphagia (KK5093801TS0), which is funded by the Federal Ministry for Economic Affairs and Energy. This project is based on a cooperation with Physiomed Elektromedizin., (Copyright © 2022 Miller et al.)

Purpose: To investigate whether Neuromuscular Electrical Stimulation (NMES) simultaneously applied on the quadriceps (Q) and gluteal (G) muscles, as compared to single Q-stimulation alters the knee extensor force production and discomfort., Methods: A total of 11 healthy participants (6 females), with normal weight and age between 19 and 54 years were included. The unilateral, isometric maximal voluntary contraction (MVC) was assessed for each participant in an isokinetic dynamometer (Biodex, system 3). NMES was, in a randomized order, applied only on the Q-muscle and on the Q- and G-muscles (QG) simultaneously. NMES-intensity was increased stepwise until the maximal tolerable level was reached regarding discomfort, graded according to the visual analogue scale (VAS). VAS and the % of MVC produced by NMES, were registered for each level, expressed as median (inter-quartile range)., Results: The maximum tolerated NMES-intensity applied on Q compared to QG resulted in equally high discomfort, 8.0 (6.0-9.0) vs 8.0 (6.3-9.0), and in equivalent knee extensor force production, 36.7 (29.9-47.5) and 36.2 (28.9-49.3), respectively, in % of MVC. At 20% of MVC, NMES applied on Q compared to QG resulted in equal acceptable discomfort, 3.0 (2.0-4.5) vs 3.0 (3-5.5), and comparable intensity levels, 41.5 (38.0-45.8) vs 43.5 (37.0-48.8), respectively., Conclusions: Simultaneous QG-NMES, as compared to single Q-NMES, does not seem to affect the knee extensor force production or discomfort. Q-NMES, without voluntary muscle contraction, can with an acceptable level of discomfort result in at least 20% of MVC., (© 2022. The Author(s).)

Objectives: To describe the influence of stimulus parameters on aberrant facial nerve stimulation in cochlear implant users., Methods: Retrospective case series (three ears - two patients). Cochlear implant patients with severe facial nerve stimulation and degraded speech comprehension who underwent re-implantation with Neuro Zti EVO (Oticon Medical)., Results: In all three ears, side effects evoked by aberrant facial nerve stimulation could be resolved and thereby speech comprehension was improved., Conclusions: Aberrant facial nerve stimulation in cochlear implant patients was successfully resolved by re-implantation. We hypothesize that one or more of the specific stimulus paramet ers are responsible for this success: combined common ground and monopolar stimulation mode, asymmetric pulse waveform with active anodic leading first phase followed by slow capacitive discharge, and pulse width modulation for loudness coding.

Background: Pressure ulcers (PUs) on the buttocks are among the most common secondary complications in individuals with chronic spinal cord injury (SCI). PUs can result from sitting for extended periods, disuse atrophy, increased sitting pressure and reduced circulation. Compared with usual care, activation of paralysed muscles using electrical stimulation (ES) has been shown to markedly increase paralysed muscle mass, improve circulation of skin and muscle and improve sitting pressure distribution. ES might therefore be a useful method to reduce PU incidence., Methods: A multicentre randomized controlled trial (SCI PREVOLT) will be conducted with an economic and process evaluation alongside. One hundred participants with a SCI in the chronic phase and a minimal incidence of 1 PU in the last 5 years will be recruited from rehabilitation centres across the Netherlands. Participants will be stratified by centre and age and randomized to the intervention or control group. The intervention group will use ES at least 1 h/day during at least 4 times a week for 1 year next to usual care. The control group will only receive usual care. The primary outcome is the incidence of PUs, measured by a blinded person assessing the presence or absence of a PU on the buttocks on a photo made by the participant or his/her caregiver. The incidence of a PU will be evaluated every 2 weeks. Secondary outcomes include interface pressure distribution, blood flow in the profunda femoris artery, muscle thickness of the hamstrings and gluteal muscles and questionnaires about different dimensions of life, e.g. participation and quality of life. Secondary outcomes will be measured at baseline and 3, 6, 9 and 12 months after randomization., Discussion: This study will assess if electrical stimulation is a (cost-)effective method to prevent PUs and reduce the risk factors of getting PUs. If ES is effective and cost-effective compared with usual care, ES could be implemented in daily treatment of individuals with a SCI., Trial Registration: Netherlands Trials Register NTR NL9469 . Registered on 26 May 2021., (© 2022. The Author(s).)

Neuromuscular electrical stimulation (NMES) can be delivered in a conventional form (CONV NMES ) and using relatively wide-pulses and high-frequencies (WPHF NMES ). WPHF NMES is proposed to reduce contraction fatigability and generate larger contractions with less discomfort than CONV NMES ; however, there are no systematic reviews to guide the selection of NMES types. This systematic review compared the effects of CONV NMES versus WPHF NMES on contraction fatigability, strength adaptations, and perceived discomfort in clinical and non-clinical populations. Eight studies were included. When averaged across all non-clinical participants in individual short- and long-term studies, there was either no difference between CONV NMES and WPHF NMES for all outcomes or WPHF NMES produced more fatigability. In a subset of non-clinical participants ("responders"), however, WPHF NMES reduced contraction fatigability during a single session. Long-term studies found no differences between protocols for strength adaptations in non-clinical participants and those with multiple sclerosis. We concluded that WPHF NMES reduces contraction fatigability only in the short-term studies and in non-clinical responder participants and may exacerbate fatigability in non-responders. This review was registered in the prospective international registry of systematic reviews/PROSPERO (Registration Number: CRD42020153907). Novelty: WPHF NMES may reduce fatigue in some participants and exacerbate fatigue in others. There were no differences in long-term studies between WPHF and CONV NMES on strength adaptations. Future high-quality research is needed to optimize outcomes of NMES-based programs.

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that develops from exposure to trauma, mostly when normal psychological mechanisms fail. Studies have shown that people who have PTSD are susceptible to developing dementia, mostly Alzheimer's disease (AD), suggesting common underlying risk factors in the comorbidity. However, data elucidating links between these conditions is scarce. Here we show that footshock stress exacerbates AD-like pathology. To induce a trauma-like condition, the rats were exposed to multiple intense footshocks followed by a single reminder. This was followed by bilateral intrahippocampal lesions with amyloid-beta (Aβ) (1-42), to model AD-like pathology. We found that footshocks increased anxiety behavior and impaired fear memory extinction in Aβ(1-42) lesioned rats. We also found a reduced expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD (P) H: quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and an increased expression of Kelch-like ECH-associated protein 1 (Keap1) in the amygdala and hippocampus. Furthermore, oxidative stress level was sustained, which was associated with increased apoptosis in the amygdala and hippocampus. Our finding suggests that AD-like pathology can induce oxidative changes in the amygdala and hippocampus, which can be exaggerated by footshock stress., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Post-traumatic stress disorder (PTSD) is a debilitating and chronic fear-based disorder. Pavlovian fear conditioning protocols have long been utilised to manipulate and study these fear-based disorders. Contextual fear conditioning (CFC) is a particular Pavlovian conditioning procedure that pairs fear with a particular context. Studies on the neural mechanisms underlying the development of contextual fear memories have identified the medial prefrontal cortex (mPFC), or more specifically, the pre-limbic cortex (PL) of the mPFC as essential for the expression of contextual fear. Despite this, little research has explored the role of the PL in contextual fear memory maintenance or examined the role of neuronal mitogen-activated protein kinase (pMAPK; ERK 1/2), brain-derived neurotrophic factor (BDNF), and IBA-1 in microglia in the PL as a function of Pavlovian fear conditioning. The current study was designed to evaluate how the maintenance of two different long-term contextual fear memories leads to changes in the number of immune-positive cells for two well-known markers of neural activity (phosphorylation of MAPK and BDNF) and microglia (IBA-1). Therefore, the current experiment is designed to assess the number of immune-positive pMAPK and BDNF cells, microglial number, and morphology in the PL following CFC. Specifically, 2 weeks following conditioning, pMAPK, BDNF, and microglia number and morphology were evaluated using well-validated antibodies and immunohistochemistry ( n = 12 rats per group). A standard CFC protocol applied to rats led to increases in pMAPK, BDNF expression and microglia number as compared to control conditions. Rats in the unpaired fear conditioning (UFC) procedure, despite having equivalent levels of fear to context, did not have any change in pMAPK, BDNF expression and microglia number in the PL compared to the control conditions. These data suggest that alterations in the expression of pMAPK, BDNF, and microglia in the PL can occur for up to 2 weeks following CFC. Together the data suggest that MAPK, BDNF, and microglia within the PL of the mPFC may play a role in contextual fear memory maintenance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chaaya, Wang, Jacques, Beecher, Chaaya, Battle, Johnson, Chehrehasa, Belmer and Bartlett.)

Noisy galvanic vestibular stimulation (nGVS) at imperceptible levels has been shown to reduce body sway. This reduction was commonly attributed to the mechanism of stochastic resonance (SR). However, it has never been explicitly tested whether nGVS-induced effects on body sway consistently follow a SR-like bell-shaped performance curve with maximal reductions in a particular range of noise intensities. To test this, body sway in 21 young healthy participants was measured during varying nGVS amplitudes while standing with eyes closed in 3 conditions (quiet stance, sway referencing, sinusoidal platform tilts). Presence of SR-like response dynamics in each trial was assessed (1) by a goodness-of-fit analysis using an established SR-curve model and (2) by ratings from 3 human experts. In accordance to theory, we found reductions of body sway at one nGVS amplitude in most trials (75-95%). However, only few trials exhibited SR-like bell-shaped performance curves with increasing noise amplitudes (10-33%). Instead, body sway measures rather fluctuated randomly across nGVS amplitudes. This implies that, at least in young healthy adults, nGVS effects on body sway are incompatible with SR. Thus, previously reported reductions of body sway at particular nGVS intensities more likely result from inherent variations of the performance metric or by other yet unknown mechanisms.

Memories of adverse events can be maladaptive when they lead to exaggerated fear, as observed in post-traumatic stress disorder (PTSD). Fear conditioning and fear sensitization are learning processes thought to play a role in fear-related disorders, and only few animal studies have evaluated the relationship between the associative and non-associative fear memory components on the development and maintenance of PTSD-like behavioral changes. Here we assessed the effects of a single dose of propranolol (10 mg/kg) or saline after fear memory retrieval on the long-term behavioral responses induced by severe stress in male rats. Animals were submitted to contextual fear conditioning (delayed shock group) or not (non-shock group) and underwent fear memory retrieval followed by propranolol or saline administration two weeks later. Rats were then evaluated in different behavioral tests to assess the expression of the conditioned fear response, anxiety-like and exploratory behaviors, and fear response after the presentation of unknown acoustic stimulus. Post-retrieval propranolol did not disrupt the subsequent expression of neither conditioned fear response nor the exploratory deficit and fear sensitization response, indicating that propranolol failed to mitigate long-term behavioral changes induced by severe stress in rats., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study is to investigate changes in autonomic activities and systemic circulation generated by surgical manipulation or electrical stimulation to the human brain stem., Methods: We constructed a system that simultaneously recorded microsurgical field videos and heart rate variability (HRV) that represent autonomic activities. In 20 brain stem surgeries recorded, HRV features and sites of surgical manipulation were analyzed in 19 hypertensive epochs, defined as the periods with transient increases in the blood pressure. We analyzed the period during electrical stimulation to the ponto-medullary junction, performed for the purpose of monitoring a cranial nerve function., Results: In the hypertensive epoch, HRV analysis showed that sympathetic activity predominated over the parasympathetic activity. The hypertensive epoch was more associated with surgical manipulation of the area in the caudal pons or the rostral medulla oblongata compared to controls. During the period of electrical stimulation, there were significant increases in blood pressures and heart rates, accompanied by sympathetic overdrive., Conclusions: Our results provide physiological evidence that there is an important autonomic center located adjacent to the ponto-medullary junction., Significance: A large study would reveal a candidate target of neuromodulation for disorders with autonomic imbalances such as drug-resistant hypertension., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Cortico-cortical evoked potential (CCEP) by single-pulse electrical stimulation (SPES) is useful to investigate effective connectivity and cortical excitability. We aimed to clarify the safety of CCEPs., Methods: We retrospectively analyzed 29 consecutive patients with intractable partial epilepsy undergoing chronic subdural grid implantation and CCEP recording. Repetitive SPES (1 Hz) was systematically applied to a pair of adjacent electrodes over almost all electrodes. We evaluated the incidences of afterdischarges (ADs) and clinical seizures., Results: Out of 1283 electrode pairs, ADs and clinical seizures were observed in 12 and 5 pairs (0.94% and 0.39%, per electrode pair) in 7 and 3 patients (23.3% and 10.0%, per patient), respectively. Of the 18-82 pairs per patient, ADs and clinical seizures were induced in 0-4 and 0-3 pairs, respectively. Stimulating 4 SOZ (seizure onset zone) (2.5%) and 8 non-SOZ pairs (0.75%) resulted in ADs. We observed clinical seizures in stimulating 4 SOZ (2.5%) and 1 non-SOZ pair (0.09%). The incidence of clinical seizures varied significantly between SOZ and non-SOZ stimulations (p = 0.001), while the difference in AD incidence tended towards significance (p = 0.058)., Conclusion: Although caution should be taken in stimulating SOZ, CCEP is a safe procedure for presurgical evaluation., Significance: CCEP is safe under the established protocol., Competing Interests: Declaration of Competing Interest Department of Epilepsy, Movement Disorders and Physiology (Kyoto University Graduate School of Medicine) is the Industry-Academic Collaboration Courses, supported by Eisai Co., Ltd., NIHON KOHDEN CORPORATION, Otsuka Pharmaceutical Co., and UCB Japan Co., Ltd., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Animal studies have shown that the prediction error (PE) signal that drives fear extinction learning is encoded by phasic activity of midbrain dopamine (DA) neurons. Thus, the extinction PE resembles the appetitive PE that drives reward learning. In humans, fear extinction learning is less well understood. Using computational neuroimaging, a previous study from our group reported hemodynamic activity in the left ventral putamen, a subregion of the ventral striatum (VS), to correlate with a PE function derived from a formal associative learning model. The activity was modulated by genetic variation in a DA-related gene. To conceptually replicate and extend this finding, we here asked whether an extinction PE (EPE) signal in the left ventral putamen can also be observed when genotype information is not taken into account. Using an optimized experimental design for model estimation, we again observed EPE-related activity in the same striatal region, indicating that activation of this region is a feature of human extinction learning. We further observed significant EPE signals across wider parts of the VS as well as in frontal cortical areas. These results may suggest that the prediction errors during extinction learning are available to larger parts of the brain, as has also been observed in human neuroimaging studies of reward PE signaling. Conclusive evidence that the human EPE signal is of DAergic nature is still outstanding., Competing Interests: Declaration of Competing interest The authors declare no financial and non-financial conflicts of interest. R.K. receives advisory honoraria from JoyVentures, Herzlia, Israel., (Copyright © 2021. Published by Elsevier Inc.)

Probable mechanism behind the neuronal ephaptic coupling is investigated based on the introduction of "Brain"-triggered potential excitation signal smartly with a specific very low frequency (VLF) waves as a neuronal motor toolkit. Detection of this electric motor toolkit is attributed to in-vitro precise analyses of a neural network of snail, along to the disconnected snail's neuronal network as a control. This is achieved via rapid (real-time) electrical signals acquisition by blind patch-clamp method during micro-electrode implanting in the neurons at the gigaseal conditions by the surgery operations. This process is based on its waveform (potential excitation signal) detection by mathematical curve fitting process. The characterized waveform of this electrical signal is "Saw Tooth" that is smartly stimulated, alternatively, by the brain during triggering the action potential's (AP's) hyperpolarization zone at a certain time interval at the several µs levels. Triggering the neuron cells results in (1) observing a positive shift (10.0%, depending on the intensity of the triggering wave), and (2) major promotion in the electrical current from sub nano (n) to micro (µ) amper (nA, µA) levels. Direct tracing the time domain (i.e., electrical signal vs. time) and estimation of the frequency domain (diagram of electrical response vs. the applied electrical frequencies) by the "Discrete Fast Fourier Transform" algorithm approve the presence of bilateral and reversible electrical currents between axon and dendrite. This mechanism therefore opens a novel view about the neuronal motor toolkit mechanism, versus the general knowledge about the unilateral electrical current flow from axon to dendrite operations in as neural network. The reliability of this mechanism is evaluated via (1) sequential modulation and demodulation of the snail's neuron network by a simulation electrical functions and sequentially evaluation of the neuronal current sensitivity between pA and nA (during the promotion of the signal-to-noise ratio, via averaging of 30 ± 1 (n = 15) and recycling the electrical cycles before any neuronal response); and (2) operation of the process on the differentiated stem cells. The interstice behavior is attributed to the effective role of Ca 2+ channels (besides Na + and K + ionic pumping), during hyper/hypo calcium processes, evidenced by inductively coupled plasma as the selected analytical method. This phenomenon is also modeled during proposing quadrupole well potential levels in the neuron systems. This mechanism therefore points to the microprocessor behavior of neuron networks. Stimulation of the neuronal system based on this mechanism, not only controls the sensitivity of neuron electrical stimulation, but also would open a light window for more efficient operating the neuronal connectivity during providing interruptions by phenomena such as neurolysis as well as an efficient treatment of neuron-based disorders.

Foot electrical stimulation (FES) has been considered as a classic stressor that can disturb homeostasis. Acute anemia was observed in the model induced by FES. The aim of this study was to explore the role of inflammatory cytokines underlying the acute anemia and gastrointestinal (GI) mucosal injury in the FES. Twenty-four male Kunming mice (20 ± 2 g) were randomly divided into control group and experimental group. The mice were placed in a footshock chamber that can generate 0.5 mA electrical impulse periodically for 0.5 h. After the process, red blood cell count, hemoglobin concentration and hematocrit, the levels of corticotropin releasing hormone (CRH) in serum and hypothalamus, and adrenocorticotropic hormone (ACTH) in serum and pituitary were detected separately. In addition, we investigated the expressions of inflammatory cytokines (IL-1, IL-6, TNF-α, iNOS, and IL-10) in the hypothalamus and duodenum by Polymerase Chain Reaction (PCR). Results showed that this FES model induced anemia, increased CRH and ACTH activity in the serum after the FES. Moreover, the expressions of IL-1β, IL-6, TNF-α, and iNOS were significantly increased following the process, while IL-10 was not activated. These findings suggest that anemia, the inflammatory cytokines in the hypothalamus and duodenum of the mice in the model induced by FES is closely related to GI mucosal injury/bleeding. Taken together, these results underscore the importance of anemia, GI mucosal injury/bleeding and stress, future studies would be needed to translate these findings into the benefit of affected patients.

Deep brain stimulation is a promising treatment for severe depression, but lack of efficacy in randomized trials raises questions regarding anatomical targeting. We implanted multi-site intracranial electrodes in a severely depressed patient and systematically assessed the acute response to focal electrical neuromodulation. We found an elaborate repertoire of distinctive emotional responses that were rapid in onset, reproducible, and context and state dependent. Results provide proof of concept for personalized, circuit-specific medicine in psychiatry.

The nucleus accumbens (NAc) plays a crucial role in various mental activities, including positive and negative reinforcement. We previously hypothesized that a balance between dopamine (DA) and adenosine signals regulates the PKA-Rap1 pathway in medium spiny neurons expressing DA D1 receptors (D1R-MSNs) or D2 receptors (D2R-MSNs) and demonstrated that the PKA-Rap1 pathway in D1R-MSNs is responsible for positive reinforcement. Here, we show the role of the PKA-Rap1 pathway in accumbal D2R-MSNs in negative reinforcement. Mice were exposed to electric foot shock as an aversive stimulus. We monitored the phosphorylation level of Rap1gap S563, which leads to the activation of Rap1. Electric foot shocks increased the phosphorylation level of GluN1 S897 and Rap1gap S563 in the NAc. The aversive stimulus-evoked phosphorylation of Rap1gap S563 was detected in accumbal D2R-MSNs and inhibited by pretreatment with adenosine A2a receptor (A2aR) antagonist. A2aR antagonist-treated mice showed impaired aversive memory in passive avoidance tests. AAV-mediated inhibition of PKA, Rap1, or MEK1 in accumbal D2R-MSNs impaired aversive memory in passive avoidance tests, whereas activation of this pathway potentiated aversive memory. Optogenetic inactivation of mesolimbic DAergic neurons induced place aversion in real-time place aversion tests. Aversive response was attenuated by inhibition of PKA-Rap1 signaling in accumbal D2R-MSNs. These results suggested that accumbal D2R-MSNs regulate aversive behaviors through the A2aR-PKA-Rap1-MEK pathway. Our findings provide a novel molecular mechanism for regulating negative reinforcement., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Alteration of immune status in the central nervous system (CNS) has been implicated in the development of post-traumatic stress disorder (PTSD). However, the nature of overall changes in brain immunocyte landscape in PTSD condition remains unclear., Methods: We constructed a mouse PTSD model by electric foot-shocks followed by contextual reminders and verified the PTSD-related symptoms by behavior test (including contextual freezing test, open-field test, and elevated plus maze test). We examined the immunocyte panorama in the brains of the naïve or PTSD mice by using single-cell mass cytometry. Microglia number and morphological changes in the hippocampus, prefrontal cortex, and amygdala were analyzed by histopathological methods. The gene expression changes of those microglia were detected by quantitative real-time PCR. Genetic/pharmacological depletion of microglia or minocycline treatment before foot-shocks exposure was performed to study the role of microglia in PTSD development and progress., Results: We found microglia are the major brain immune cells that respond to PTSD. The number of microglia and ratio of microglia to immunocytes was significantly increased on the fifth day of foot-shock exposure. Furthermore, morphological analysis and gene expression profiling revealed temporal patterns of microglial activation in the hippocampus of the PTSD brains. Importantly, we found that genetic/pharmacological depletion of microglia or minocycline treatment before foot-shock exposure alleviated PTSD-associated anxiety and contextual fear., Conclusion: Our results demonstrated a critical role for microglial activation in PTSD development and a potential therapeutic strategy for the clinical treatment of PTSD in the form of microglial inhibition.

We examined the neural mechanisms for increases in regional cerebral blood flow (rCBF) in the neocortex associated with mastication, focusing on the cortical vasodilative system derived from the nucleus basalis of Meynert (NBM). In pentobarbital-anesthetized rats, parietal cortical rCBF was recorded simultaneously with electromyogram (EMG) of jaw muscles, local field potentials of frontal cortex, multi-unit activity of NBM neurons, and systemic mean arterial pressure (MAP). When spontaneous rhythmic EMG activity was observed with cortical desynchronization, an increase in NBM activity and a marked rCBF increase independent of MAP changes were observed. A similar rCBF increase was elicited by repetitive electrical stimulation of unilateral cortical masticatory areas. The magnitude of rCBF increase was partially attenuated by administration of the GABAergic agonist muscimol into the NBM. The rCBF increase persisted after immobilization with systemic muscle relaxant (vecuronium). rCBF did not change when jaw muscle activity was induced by electrical stimulation of the pyramidal tract. The results suggest that activation of NBM vasodilator neurons contributes at least in part to the rCBF increase associated with masticatory muscle activity, and that the NBM activation is induced by central commands from the motor cortex, independently of feedback from brainstem central pattern generator or contracting muscles.

Aim: Fear conditioning tests are intended to elucidate a subject's ability to associate a conditioned stimulus with an aversive, unconditioned stimulus, such as footshock. Among these tests, a paradigm related to precise cortical functions would be increasingly important in drug screening for disorders such as schizophrenia and dementia. Therefore, we established a new fear conditioning paradigm using a visual cue in mice. In addition, the validity of the test was evaluated using a genetically engineered mouse, heterozygous deficient in Mdga1 (Mdga1+/-), which is related to schizophrenia., Results: Mice were given footshocks associated with a visual cue of moving gratings at training in 25-minute sessions. The mice showed the conditioned response of freezing behavior to the visual stimulus at testing 24 hours after the footshocks. In the test for validation, the Mdga1+/- deficient mice showed significantly less freezing than wild-type mice., Conclusion: The visually cued fear conditioning paradigm with moving gratings has been established, which is experimentally useful to evaluate animal cortical functions. The validity of the test was confirmed for Mdga1-deficient mice with possible deficiency in cortical functions., (© 2020 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Society of NeuropsychoPharmacology.)

In exposure for chronic pain, avoidance is often forbidden (extinction with response prevention; RPE) to prevent misattributions of safety. Although exposure is an effective treatment, relapse is common. Little is known about the underlying mechanisms of return of pain-related avoidance. We hypothesized that pain-related avoidance would recover when becoming available again after RPE and after unexpected pain episodes ("reinstatement"), especially when restricting avoidance during RPE (compared to instructing not to use it). In an operant pain-related avoidance conditioning paradigm, healthy volunteers used a robotic arm to perform various arm reaching movements differing in pain-effort trade-off. During acquisition, participants learned to avoid pain by performing more effortful movements. During RPE they only performed the formerly pain-associated movement under extinction, and were either forbidden (Restricted group) or merely instructed (Instructed group) not to perform other movements. One day later, we tested spontaneous recovery and reinstatement of pain-related fear and avoidance with availability of all movements. Results showed that pain-related fear and avoidance re-emerge after RPE, though not to pretreatment levels. The reinstatement manipulation had no additional effect. No group differences were observed. We discuss findings in the context of learning processes in (chronic) pain disability and relapse prevention in chronic pain treatment. Perspective: Using experimental models of relapse, we investigated the return of pain-related avoidance behavior after extinction with response prevention. Findings are potentially informative for clinicians performing exposure treatment with chronic pain patients., (Copyright © 2020 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Avoidance behavior is protective, yet in the absence of genuine bodily threat, it may become disabling. Therefore, we investigated whether avoidance generalizes to novel safe contexts based on the similarity with the acquisition context. Healthy participants performed arm movements using a robotic arm to reach a target. Three trajectories (T1-3) led to the target. During acquisition, a painful stimulus could be partly/completely prevented by performing more effortful trajectories (ie, longer and more force needed), T2/T3, in the pain-avoidance context (eg, black background); in the yoked context (eg, white background), the same reinforcement schedule was applied irrespective of the chosen trajectories. Generalization of avoidance was tested in 2 novel contexts (eg, shades of gray backgrounds). We assessed self-reported pain-expectancy and pain-related fear for all trajectories, and avoidance behavior (ie, maximal deviation from T1). Results confirm that fear and expectancy ratings reflect the response-outcome contingencies and differential learning selectively generalized to the novel context resembling the original pain-avoidance context. Furthermore, a linear trend in avoidance behavior across contexts emerged, which is indicative of a generalization gradient. Participants avoided more in the context resembling the original pain-avoidance context than in the one resembling the yoked context, but this effect was not statistically significant. PERSPECTIVE: Perspective: We demonstrated acquisition of pain-related avoidance behavior in a within-subjects design, showing modulation of pain-related fear and pain-expectancy by context and providing limited evidence that avoidance selectively generalizes to novel, similar contexts. These results provide insight regarding the underlying mechanisms of the spreading of protective behavior in chronic pain patients., (Copyright © 2020 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Although relatively rare, human-shark interactions and sharks bites are increasing globally, which has led to the development of various mitigation measures. Electric shark deterrents (ESDs) have, so far, been the most effective personal deterrents, but have only been scientifically tested on one of the species most frequently responsible for shark bites, i.e. white shark (Carcharodon carcharias). We tested the effectiveness of five ESDs (E-Shark Force, NoShark, Rpela v2, Freedom + Surf, Freedom + Surf-Shortboard) on bull sharks, Carcharhinus leucas, over a period of 21 days in September 2019, in New Caledonia. Standardised bait was attached 30 cm below an experimental board that had an active ESD for up to 15 min, or until a bull shark touched the bait or the board. We compared the numbers of baits taken, numbers of passes and reactions around the board, as well as the distance between the sharks and the board among ESDs and against a control board with bait and no active ESD. The Freedom + Surf was the most effective ESD, reducing the amounts of baits taken by 42.3%, while the Rpela v2 and Freedom + Surf-Shortboard also significantly reduced the number of baits taken by 16.5% and 16.2% respectively. Mean distance between sharks and the bait was not affected by the ESDs, but the number of approaches and the proportion of reactions were both significantly higher when the Freedom + Surf was active compared to other ESDs. The effectiveness of all ESDs decreased over time, with the likelihood of the bait being taken increasing and the number of approaches and distance between sharks and the bait decreasing. Our findings show that the ability of ESDs to deter bull shark varies between products, with the Freedom + Surf resulting in the most behavioural changes, followed by the Rpela v2 and Freedom + Surf-Shortboard. However, none of the products tested completely stopped sharks from taking the bait.

Purpose: In this study, the aim was to evaluate the safety of transcorneal electrical stimulation (TES) treatment in retinitis pigmentosa (RP) patients and to investigate the effect of TES to the visual acuity (VA), visual field (VF), and multifocal electroretinogram (mfERG) findings. Methods: Two hundred two eyes of 101 RP patients with different stages were studied. TES was applied for 30 min once a week for 8 consecutive weeks. Two hundred eyes of 100 RP patients were enrolled as control. After the 2-month TES therapy sessions, patients were followed for 4 months without treatment. Examinations were done at the baseline before TES treatment and 1 and 6 months after the treatment. Best-corrected VA (BCVA), color fundus photography, VF test, optical coherence tomography, and mfERG tests were done at each visit. Results: The mean BCVA and VF tests improved 1 month after the beginning of TES treatment and the improvements were statistically significant ( P  < 0.05). There was an improvement in p1 wave amplitude in rings 1, 2, and 3 at the first month. The latency of the p1 wave showed a statistically significant shortening in rings 1 and 2. These improvements partially disappeared at 6-month follow-up. There were no serious ocular side effects related to the therapy. Mild dry eye symptoms were observed, which were revealed by artificial tears. Conclusions: TES is a safe therapy without any serious advers effects. Although it can improve VA and VF of RP patients, the beneficial effects could be transient and repeated sessions can be necessary for maintaining the efficiency.

Anxiety patients overgeneralize fear responses, possibly because they cannot distinguish between cues never been associated with a threat (i.e., safe) and threat-associated cues. However, as contexts and not cues are discussed as the relevant triggers for prolonged anxiety responses characterizing many anxiety disorders, we speculated that it is rather overgeneralization of contextual anxiety, which constitutes a risk factor for anxiety disorders. To this end, we investigated generalization of conditioned contextual anxiety and explored modulatory effects of anxiety sensitivity, a risk factor for anxiety disorders. Fifty-five participants underwent context conditioning in a virtual reality paradigm. On Day 1 (acquisition), participants received unpredictable mildly painful electric stimuli (unconditioned stimulus, US) in one virtual office (anxiety context, CTX+), but never in a second office (safety context, CTX-). Successful acquisition of conditioned anxiety was indicated by aversive ratings and defensive physiological responses (i.e., SCR) to CTX+ vs CTX-. On Day 2 (generalization), participants re-visited both the anxiety and the safety contexts plus three generalization contexts (G-CTX), which were gradually dissimilar to CTX+ (from 75 to 25%). Generalization of conditioned anxiety was evident for ratings, but less clear for physiological responses. The observed dissociation between generalization of verbal and physiological responses suggests that these responses depend on two distinct context representations, likely elemental and contextual representations. Importantly, anxiety sensitivity was positively correlated with the generalization of reported contextual anxiety. Thus, this study demonstrates generalization gradients for conditioned contextual anxiety and that anxiety sensitivity facilitates such generalization processes suggesting the importance of generalization of contextual anxiety for the development of anxiety disorders.

Lack of control over significant events may induce a state of learned helplessness that is characterized by cognitive, motivational, and affective deficits. Although highly relevant in the pathogenesis of several mental disorders, the extent of the cognitive deficits induced by experiences of uncontrollability and the neural mechanisms underlying such deficits in humans remain poorly understood. Using functional magnetic resonance imaging (fMRI), we tested here whether uncontrollability over aversive events impairs subsequent working memory performance and, if so, which neural processes are involved in such deficits. We assessed working memory and the involved neurocircuitry in the MRI scanner before and after participants underwent a task in which they could either learn to avoid electric shocks or had no instrumental control over shocks. Our results show that subjective, but not objective, uncontrollability over aversive events impaired working memory performance. This impact of subjective uncontrollability was linked to altered prefrontal and parahippocampal activities and connectivity as well as decreased crosstalk between frontoparietal executive and salience networks. Our findings show that the perceived uncontrollability over aversive events, rather than the aversive events themselves or the actual, objective control over them, disrupts subsequent working memory processes, most likely through altered crosstalk between prefrontal, temporal, and parietal areas., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

(1) The primary involvement in stress-induced disturbances in skeletal muscles is assigned to the release of glucocorticoids (GCs). The current study aims to investigate the impact of the biphasic action of the chronic stress response (CSR) induced by the electrical stimulation of the bed nucleus of the stria terminalis (BST) effects on muscle atrophy and aerobic energy metabolism in soleus (SOL) and extensor digitorum longus (EDL) muscles. (2) Male Wistar rats ( n = 17) were used. The rats were divided randomly into three groups: the BST two weeks (ST2), four weeks (ST4), and the sham (SHM) electrically stimulated group. The plasma corticosterone (CORT) and irisin concentration were measured. Glucocorticoid and mineralocorticoid receptors (GR and MR), 11β-hydroxysteroid dehydrogenase type 1 and 2 (HSD11B1 and HSD11B2), atrogin-1, and insulin-like growth factor-1 (IGF-1) level were determined in SOL and EDL muscles. Citrate synthase (CS) activity was measured in both muscles. (3) We found elevated plasma concentration of CORT and irisin, raised the level of GR in SOL muscle, and the higher level of MR in both muscles in the ST4 group. The level of HSD11B1 was also higher in the ST4 group compared to the SHM group. Moreover, we observed increased activity of CS in SOL. (4) We suggest that biphasic action of the glucocorticoid induced by the CSR occurs and causes dysregulation of proteins involved in muscle atrophy and aerobic energy metabolism. Our findings potentially contribute to a better understanding of the mechanisms by which GCs and the CSR may regulate muscle atrophy and energy preservation of the red muscle.

Since a rapidly increasing number of neurostimulation devices are used clinically to modulate specific neural functions, the impact of electrical stimulation on targeted neural structure and function has become a key issue. In particular, the specific effect of electrical stimulation via a cochlear implant (CI) on inner hair cell (IHC) synapses remains unclear. Importantly, CI candidacy has recently expanded to include patients with partial hearing loss. Unfortunately, some CI recipients experience progressive hearing loss after activation of electrical stimulation. The mechanism(s) accounting for loss of residual hearing following electrical stimulation is unknown. Here normal-hearing guinea pigs were implanted with customized CIs. Intracochlear electrical stimulation with an intensity equal to or above electrically evoked compound action potential (ECAP) threshold decreased the excitability of auditory nerve. Furthermore, the number of synapses between IHCs and the afferent spiral ganglion neurons (SGNs) also decreased after electrical stimulation with higher intensities. However, no significant change was observed in the packing density and perikaryal area of SGNs as well as the quantity of hair cells. These results carry important implications for use of CIs in patients with residual hearing and for an increasing number of patients treated with other neurostimulation devices. Notably, the results were based on acute electrical stimulation. Considering the complex interaction between CIs and targeted tissues, it is urgent to conduct further research to clarify whether the similar changes could be induced by chronic electrical stimulation., (© 2019 Wiley Periodicals, Inc.)

Primary somatosensory cortex (S1) is involved in pain processing and thus its suppression using neuromodulatory techniques such as continuous theta burst stimulation (cTBS) might be a potential pain management strategy in patients with neuropathic pain. cTBS over S1 is known to elevate pain threshold in young adults. However, the time course of this after-effect is unknown. Furthermore, the effect of cTBS over S1 on pain threshold might be confounded by changes in the excitability of primary motor cortex (M1), an area known to be involved in pain processing, due to spread of current. Therefore, whether S1 plays a role in pain processing independent of M1 also remains unknown. The corticospinal excitability (CSE) can provide a measure of M1 excitability because cTBS over M1 is known to reduce CSE. Here, we studied the time-course of the effects of MRI-guided cTBS over S1 on electrical pain threshold (EPT) and CSE. Ten healthy young adults received cTBS over S1 and sham stimulation in counterbalanced sessions at least 5 days apart. EPT and CSE were recorded before and following cTBS over S1. We assessed each measure once before stimulation and then every 10 min starting immediately after stimulation until 40 min. cTBS over S1 elevated EPT compared to sham stimulation with the after-effect lasting for 40 min. We observed no change in CSE following cTBS and sham stimulation. Our findings suggest that cTBS over S1 can elevate EPT for 40 min without altering M1 excitability., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In mammals, the insular cortex plays an important role in autonomic regulation. In patients with insular epilepsy, seizures are always accompanied by autonomic changes. Accordingly, we aimed to establish an electrical kindling model in autonomic-mediating areas of the insular cortex, and to conduct a long-term observation of epileptic genesis in these animals until sudden unexpected death. To establish this model in adult rats, we implanted stimulation electrodes in the granular cell layer of the insular cortex, which controls the heart rate (HR) and respiratory rate (RR). Subsequently, seizure was induced successfully in 92.3 % of the rats, and typical autonomic changes were observed during these seizures. Interestingly, the model was established more easily in older rats, and the rats in which electrical stimulation led to a greater reduction in the HR. Moreover, death occurred in 25 % of the kindled rats. In conclusion, our kindling model demonstrates the ability of insular cortex stimulation to generate epilepsy. Our model thus offers a practical tool for studies of the role of the insular cortex in sudden unexpected death in epilepsy., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: This paper investigates an ultrasound imaging-based non-invasive methodology to quantitatively assess changes in muscle contractility due to the fatigue induced by neuromuscular electrical stimulation (NMES)., Methods: Knee extension experiments on human participants were conducted to record synchronized isometric knee force data and ultrasound images of the electrically stimulated quadriceps muscle. The data were first collected in a pre-fatigue stage and then in a post-fatigue stage. Ultrasound images were processed using a contraction rate adaptive speckle tracking algorithm. A two-dimensional strain measure field was constructed based on the muscle displacement tracking results to quantify muscle contractility., Results: Analysis of the strain images showed that, between the pre-fatigue and post-fatigue stages, there was a reduction in the strain peaks, a change in the strain peak distribution, and a decrease in an area occupied by the large positive strain., Conclusion: The results indicate changes in muscle contractility due to the NMES-induced muscle fatigue., Significance: Ultrasound imaging with the proposed methodology is a promising tool for a direct NMES-induced fatigue assessment and facilitates new strategies to alleviate the effects of the NMES-induced fatigue.

Clinical observations have often reported that patients with seizures arising from limbic structures on the right side of the brain have a higher incidence of emotional disturbances, such as fear and anxiety, than those who have seizures lateralized to limbic structures on the left side. However, there have been some inconsistent reports regarding the presence of these laterality effects. The use of animal models of epilepsy can help circumvent many of the methodological and ethical issues that arise from human clinical studies. In the present study, we examined the unique contribution of left- or right-sided long-term kindling of the amygdala on the development of interictal emotional disturbances. Following kindling to 99 electrical stimulations, male kindled and control rats were examined on a series of behavioral tests - open-field exploration, elevated plus maze, forced swim, and social interaction. Our results revealed that long-term amygdala kindling, irrespective of the hemisphere stimulated, increased general behavioral hyperactivity and fearful behavior. Interestingly, rats that were kindled from the left amygdala showed greater social avoidance and defensive behaviors during interactions with another kindled conspecific. To examine the brain structures that support long-term kindling, we also examined the expression of the immediate early gene product Fos 1 h after rats received their last electrical stimulation. Compared with control rats, kindled rats had increased Fos expression in several brain regions (e.g., piriform, frontal motor cortex, perirhinal cortex) involved in the generation and development of epilepsy. However, decreased Fos expression was also observed in several subregions of the hippocampus and amygdala that are known to be important fear behavior and memory. These findings suggest that both left and right amygdala kindling produce similar changes in emotional behavior and support the idea that the development of kindled fear may result from reduced activation of specific hippocampal and amygdaloid circuits., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)