Electrical Stimulation Research Articles

The Biomimetic Electrical Stimulation System Inducing Osteogenic Differentiations of BMSCs.

Electrical stimulation has been used clinically as an adjunct therapy to accelerate the healing of bone defects, and its mechanism requires further investigations. The complexity of the physiological microenvironment makes it challenging to study the effect of electrical signal on cells alone. Therefore, an artificial system mimicking cell microenvironment in vitro was developed to address this issue. In this work, a novel electrical stimulation system was constructed based on polypyrrole nanowires (ppyNWs) with a high aspect ratio. Synthesized ppyNWs formed a conductive network in the composited hydrogel which contained modified gelatin with methacrylate, providing a conductive cell culture matrix for bone marrow mesenchymal stem cells. The dual-network conductive hydrogel had improved mechanical, electrical, and hydrophilic properties. It was able to imitate the three-dimensional structure of the cell microenvironment and allowed adjustable electrical stimulations in the following system. This hydrogel was integrated with cell culture plates, platinum electrodes, copper wires, and external power sources to construct the artificial electrical stimulation system. The optimum voltage of the electrical stimulation system was determined to be 2 V, which exhibited remarkable biocompatibility. Moreover, this system had significant promotion in cell spreading, osteogenic makers, and bone-related gene expression of stem cells. RNA-seq analysis revealed that osteogenesis was correlated to Notch, BMP/Smad, and calcium signal pathways. It was proven that this biomimetic system could regulate the osteogenesis procedure, and it provided further information about how the electrical signal regulates osteogenic differentiations.

The Management of Children and Adolescents with Overactive Bladder Refractory to Treatment with Parasacral Transcutaneous Electrical Nerve Stimulation.

Although parasacral TENS (pTENS) has been employed in various centers, there is a lack of studies on how children with overactive bladder (OAB) respond after failing to complete pTENS sessions. This study aimed to describe and assess treatments for OAB in children who did not respond to pTENS. This retrospective case series examined patients aged 4-17 years. Patients were given subsequent treatment options, including: behavioral therapies; oxybutynin; imipramine; a combination of oxybutynin and imipramine; parasacral percutaneous electrical nerve stimulation (PENS); or a repeat course of pTENS. Outcomes were evaluated using the Dysfunctional Voiding Scoring System (DVSS) and the Visual Analogue Scale (VAS). Thirty children were included, with a median age of 7 years. Patients received one or more treatments. Of these, 70% underwent monotherapy. Among them, 57% experienced complete resolution of symptoms, 28% had partial resolution and were satisfied with the results, and 14% discontinued treatment. 30% out of the whole sample continued to experience bothersome symptoms. Complete response, according to initial subsequent, was achieved in: 54% with intensified behavioral therapies, 33% with oxybutynin, and 50% with imipramine alone. The median DVSS score decreased from 7.0 to 2.0 (p=0.025), while the median VAS score increased from 80 to 100 (p<0.001). Children with OAB refractory to pTENS who received structured subsequent treatments showed partial response in all cases, with complete symptom resolution in half of the patients. More intensive urotherapy, medications, or repeat pTENS in combination with oxybutinin can be effective for managing this challenging condition.

Enhanced Cochlear Coverage and Hearing Preservation in High-Frequency Hearing Loss via Electric Acoustic Stimulation with Longer Electrode

Enhanced Cochlear Coverage and Hearing Preservation in High-Frequency Hearing Loss via Electric Acoustic Stimulation with Longer Electrode

Design and construction of a GAP-43 reporter system for potential identification of effective therapeutics for peripheral nerve regeneration

Background: Peripheral nerve injury (PNI) is a condition that can result in muscle paralysis and sensory disturbances. Electrical stimulation and/or the application of exogenous neurotrophic factors and cytokines are effective at enhancing nerve regeneration and is mediated via the expression of regeneration associated genes (RAGs) such as the growth associated protein GAP-43. Therapeutic upregulation of GAP-43 has potential use as a treatment for improving recovery from PNI. Few studies have investigated the potential of increasing GAP-43 for PNI therapeutic purposes and current methods for measuring GAP-43 expression are limited. Aims and Objectives: The broader aim of this work was to construct a motor neuron-like cell model with a GAP-43 reporter system. Such a model would have potential use in screening for novel therapeutics that upregulate GAP-43 and in the optimisation of electrical stimulation treatment in combination with these therapies. The key aim of the work was to design and construct a Cas9 expressing plasmid bearing a gRNA that targets GAP-43 cleavage and a donor plasmid bearing a reporter GFP or Neo cassette flanked with 5’ and 3’ GAP-43 homology arms (HAs) to facilitate the insertion of the reporter immediately 3’ of the GAP-43 promoter via CRISPR/Cas9 homology directed repair (HDR). Such an insertion would enable quantitative measurement of endogenous expression of the GAP-43 gene. Methods and Results: To guide the Cas9 nuclease to the target location, GAP-43 gRNA oligomers were designed and cloned downstream of the U6 promoter in the Cas9 expression plasmid px330, which also expresses the Cas9 gene and the cloned gRNA when transfected into cells. For CRISPR/Cas9 HDR, the 5’ and 3’ GAP-43 HAs were amplified from mouse genomic DNA and cloned into the donor plasmid using Gibson Assembly so that they flanked the reporter cassette. Results: This work successfully constructed the Cas9 gRNA expressing plasmid to target cleavage of the GAP-43 gene in mouse cell lines and has provided the complete design and construction foundation for generation of the reporter system for the endogenous GAP-43 gene in mice.

Electrohydrodynamic Printing of Microscale Fibrous Scaffolds with a Sinusoidal Structure for Enhancing the Contractility of Cardiomyocytes.

Mimicking the curved collagenous fibers in the cardiac extracellular matrix to fabricate elastic scaffolds in vitro is important for cardiac tissue engineering. Here, we developed sinusoidal polycaprolactone (PCL) fibrous scaffolds with commendable flexibility and elasticity to enhance the contractility of primary cardiomyocytes by employing melt-based electrohydrodynamic (EHD) printing. Microscale sinusoidal PCL fibers with an average diameter of ∼10 μm were printed to mimic the collagenous fibers in the cardiac ECM. The sinusoidal PCL fibrous scaffolds were EHD-printed in a layer-by-layer manner and exhibited outstanding flexibility and elasticity compared with the straight ones. The sinusoidal PCL scaffolds provided an elastic microenvironment for the attaching and spreading of primary cardiomyocytes, which facilitated their synchronous contractive activities. Primary cardiomyocytes also showed improved gene expression and maturation on the sinusoidal PCL scaffolds under electrical stimulation for 5 days. It is envisioned that the proposed flexible fibrous scaffold with biomimetic architecture may serve as a suitable patch for tissue regeneration and repair of damaged hearts after myocardial infarction.

Impact of background input on memory consolidation

Memory consolidation involves repeated replay of new information by the hippocampus, which transfers memories to the neocortex for long-term storage. This occurs mainly during slow wave sleep, a phase characterized in the cortex by low cholinergic tone and low afferent input. High cholinergic tone has been shown to hamper memory consolidation, probably mediated by reduced network excitability (the ease of activity propagation in a network). We used cortical neuronal networks on multi electrode arrays to investigate whether low background input contributes to memory consolidation. Networks received focal electrical stimuli to memorize, with or without background afferent input (global optogenetic stimulation). Background stimulation hampered memory formation and consolidation, confirming the importance of low background input. Moreover, it lowered network excitability, similar to high cholinergic tone. These findings suggest that high network excitability is a critical feature of slow wave sleep that facilitates memory consolidation.

Effect of Electrical Stimulation of Lingual Nerve on Xerostomia: A Randomized Controlled Trial.

Xerostomia is a subjective sensation of dry mouth affecting millions of people worldwide. Current management has limitations, often causing side effects. This study aims to investigate whether electrical stimulation of the lingual nerve could offer effective relief for xerostomia sufferers. Eligible participants were randomly assigned (1:1) to either the experimental or sham group, receiving electrical stimulation of the lingual nerve (n = 24) or sham stimulation (n = 23) for 12 wk. The primary outcome is the changes in xerostomia score using a 100-mm visual analog scale throughout the therapy. Participants assessed their dryness and assigned corresponding scores, with lower scores indicating more severe dry mouth. Secondary outcomes included remission rate in dry mouth frequency, changes in stimulated/unstimulated salivary flow rate (SSFR/USFR), and changes in Oral Health Impact Profile-14 (OHIP-14) questionnaire scores, where higher scores indicate greater impact on oral quality of life. At week 12, the electrical stimulation group showed greater improvement in xerostomia score compared to the sham group, with a mean between-group difference of 13.8 (95% confidence interval [CI], 10.0-17.6). The therapeutic effect of electrical stimulation was also confirmed by secondary outcomes. The remission rate of dry mouth was higher at 12 wk in the electrical stimulation group (61.9% [95% CI, 40.9%-79.3%] vs. 28.6% [95% CI, 13.8%-50.0%]). Participants in the electrical stimulation group also experienced a greater increase in USFR, with a mean difference of 14.5 (6.1-23.0) μL/min. Moreover, they exhibited significant improvement in OHIP-14 score after 12 wk of therapy, with a mean between-group difference of -10.0 (-13.9 to -6.2). No significant difference was observed between the 2 groups for SSFR (P = 0.702). Electric stimulation offers promise as a noninvasive, nonpharmacological strategy for the management of xerostomia. Further research is needed to understand its long-term effectiveness, optimal parameters, and underlying mechanisms. The study confirmed that electrical stimulation of the lingual nerve is a promising noninvasive and nonpharmacological modality for relief of xerostomia.

Investigating the Effect of Polypyrrole-Gelatin/Silk Fibroin Hydrogel Mediated Pulsed Electrical Stimulation for Skin Regeneration.

In clinical practice to treat complex injuries, the application of electrical stimulation (ES) directly to the skin complicates the wound. In this work, the effect of a conductive hydrogel mediated electric field on skin regeneration is investigated. Polypyrrole incorporated matrices of gelatin and silk fibroin were prepared by two-step interfacial polymerization. The maximum electrical conductivity of 10-4 S cm-1 was achieved when 200 mM polypyrrole was loaded. Mechanically stable and cytocompatible hydrogels were evidenced to have antioxidant and blood compatible characteristics. Human dermal fibroblast cells responded to pulsed stimulation of 100 or 300 mV mm-1 as observed from the increased expressions of TGFβ1, αSMA, and COLIAI genes. Further, the increase in the αSMA protein expression with the magnitude of electrical stimulation also suggested transdifferentiation of the fibroblast to myofibroblast. Moreover, Raman spectroscopy identified two fingerprint regions (collagen and lipid) to differentiate ES treated and nontreated samples. Therefore, the combination of hydrogels and electrical stimulation has potential therapeutic effects for accelerating the rate of skin regeneration.

Non-Invasive Muscle Metabolism Assessment with Near-Infrared Spectroscopy and Electrical Muscle Stimulation

Background: Muscle biopsy, the gold standard for assessing muscle aerobic capacity, is an invasive procedure. Noninvasive alternatives, such as 31-phosphorus magnetic resonance spectroscopy (31P-MRS) and near-infrared spectroscopy (NIRS), provide valuable insights, with NIRS providing superior time resolution and ease of use compared with 31P-MRS. Objectives: This study aimed to evaluate muscle metabolism using a 6 s muscle contraction phase with electrical muscle stimulation (EMS) and to assess the impact of EMS on exercise performance under hyperbaric conditions with elevated oxygen pressure. Methods: This study included nine male participants (21 ± 2 years) who underwent 5 min of EMS on the forearm flexor muscle group, with muscle oxygen dynamics assessed using NIRS. For statistical analysis, the mean values between groups were assessed using paired t-tests, and associations were evaluated using Pearson’s correlation coefficient. Results: Spontaneous blood flow interruption during EMS-induced muscle activity indicated the potential for assessing muscle metabolism without disrupting external blood flow. A significant negative correlation was observed between oxygen consumption and changes in oxygenated hemoglobin levels during muscle activity under hyperbaric conditions. Conclusions: This study demonstrates that skeletal muscle metabolism can be measured using a brief 6 s quantitative EMS. Furthermore, hyperbaric exercise appears to enhance aerobic capacity by increasing the rate and availability of oxygen consumption during exercise.

Investigating premotor corticospinal excitability in fast and slow voluntary contractions of the elbow flexors.

Corticospinal excitability (CSE) increases prior to a voluntary contraction; however, the relative contributions of premotor cortical and spinal mechanisms are poorly understood. It is unknown whether the intended voluntary contractile rate affects CSE. Eighteen young, healthy participants (nine females) completed isometric elbow flexion contractions targeting 50% maximal voluntary contraction (MVC) torque, at either fast (fast as possible) or slow (25% MVC/s) contractile rates. Participants were cued to contract with warning (red) and "GO" (green) visual signals. Magnetic and electric stimulations were applied to elicit motor evoked potentials (MEPs), cervicomedullary evoked potentials (CMEPs), and M-waves, in the surface electromyogram (EMG) recorded over the biceps brachii. MEPs and CMEPs were collected at 0, 25, 50 and 75% premotor reaction time (RT - defined as the time between the "GO" cue and onset of biceps brachii EMG) and compared to a resting baseline. MEP amplitude was greater than baseline at 75% RT (p=0.009), and CMEP amplitude was significantly increased at all RT points relative to baseline (p≤0.001). However, there were no differences in MEP and CMEP amplitudes when compared between fast and slow conditions (p≥0.097). Normalized to the CMEP, there was no difference in MEP amplitude from baseline in either contractile condition (p≥0.264). These results indicate that increased premotor CSE is a spinally-mediated response. Furthermore, premotor CSE is not influenced by the intended voluntary contractile rate. CMEP amplitudes were larger for females than males within the premotor RT period (p=0.038), demonstrating that premotor spinal excitability responses may be influenced by sex.

Reinforced Magnetic-Responsive Electro-Ionic Artificial Muscles by 3D Laser-Induced Graphene Nano-Heterostructures.

Efficient ion transport and enriched responsive modals via modulating electrochemical properties of conductivity and capacitance are essential for soft electro-ionic actuators. However, cost-effective and straightforward approaches to achieve expedited fabrication of active electrode materials capable of multimodal-responsiveness remain limited. Herein, this work reports the one-step ultrafast laser direct patterning method, to readily synthesize electro- and magneto-active electrode material, derived from the unique cobalt-phosphorus co-doped core-shell heterostructures within 3D graphene frameworks, for fulfilling the dual-mode responsive electro-ionic actuators. The designed nanofiber-structured heterointerfaces across electrodes and electrolytes further promote highly efficient electron/ion transfer. The developed soft actuator exhibits superior actuation performance of peak-to-peak displacement to 13.08mm under an ultra-low ±0.5V, with doubled direct current deflection under 200 mT at 1V, an ultrafast response of 1.38 s and long-term stability (>90% retention for ≈106000 cycles), even detectable bending to ≈280µm under exceptional ±10mV. The promising demonstration of promoting differentiation and proliferation of stem cells under mechanical strain and electrical stimuli, sheds more light as well on the possibility of facilitating biomedical soft robotics with ultrahigh actuation performance.

Analog‐Digital Hybridity of Resistive Switching in Ion‐Irradiated BiFeO3 Memristor for Synergistic Neuromorphic Functionality and Artificial Learning

AbstractMemristors‐based neuromorphic devices represent emerging computing architectures to perform complex tasks by outpacing the traditional Von‐Neumann architectures in terms of speed, and energy efficiency. In this work, the resistive switching (RS) behavior of sol‐gel grown and ion‐irradiated BFO films is investigated under electrical stimulus. The Ag/BFO/FTO memristors emulate a combination of digital and analog RS behavior within a single device. The possible mechanism of analog digital hybridity is addressed by considering the formation of the conducting filament by oxygen vacancies, Ag+ ions and Schottky barrier height modulation. The ion‐irradiated BFO samples are analyzed using the Raman, XRD, and XPS studies. To uphold bioinspired synaptic actions, crucial synaptic functionalities like pair‐pulse facilitation and long‐term potentiation/depression are effectively achieved. More intricate synaptic behaviors are also demonstrated such as spike‐time‐dependent plasticity and Pavlovian classical conditioning, which represent the prominent attributes of both learning and forgetting behavior. Additionally, high pattern recognition accuracy (96.1%) is achieved in an artificial neural network simulation by using the synaptic weights of the memristors. This synergistic effect of digital and analog RS in ion‐irradiated BFO can be beneficial for the emulation of complex learning behavior as well as its incorporation into low‐power neuromorphic computing.

Clinical Efficacy of Auricular Vagus Nerve Stimulation in the Treatment of Chronic and Acute Pain: A Systematic Review and Meta-analysis.

Current guidelines for pain treatment recommend a personalized, multimodal and interdisciplinary approach as well as the use of a combination of drug and non-drug therapies. Risk factors for chronification should already be reduced in patients with acute pain, e.g., after surgery or trauma. Auricular vagus nerve stimulation (aVNS) could be an effective non-drug therapy in the multimodal treatment of chronic and acute pain. The aim of this systematic review and meta-analysis is to evaluate the clinical efficacy and safety of aVNS in treating chronic and acute pain conditions. A systematic literature search was performed regarding the application of auricular electrical stimulation in chronic and acute pain. Studies were classified according to their level of evidence (Jadad scale), scientific validity and risk of bias (RoB 2 tool) and analyzed regarding indication, method, stimulation parameters, duration of treatment and efficacy and safety. A meta-analysis on (randomized) controlled trials (using different comparators) was performed for chronic and acute pain conditions, respectively, including subgroup analysis for percutaneous (pVNS-needle electrodes) and transcutaneous (tVNS-surface electrodes) aVNS. The visual analog pain scale (VAS) was defined as primary efficacy endpoint. A total of n = 1496 patients were treated with aVNS in 23 identified and analyzed studies in chronic pain, 12 studies in acute postoperative pain and 7 studies in experimental acute pain. Of these, seven studies for chronic pain and six studies for acute postoperative pain were included in the meta-analysis. In chronic pain conditions, including back pain, migraine and abdominal pain, a statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control treatment with an effect size Hedges' g/mean difference of - 1.95 (95% confidence interval [CI]: - 3.94 to 0.04, p = 0.008) could be shown and a more favorable effect in pVNS compared to tVNS (- 5.40 [- 8.94; - 1.85] vs. - 1.00 [- 1.55; - 0.44]; p = 0.015). In acute pain conditions, single studies showed significant improvements with aVNS, e.g., in kidney donor surgery or tonsillectomy but, overall, a non-statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control with - 0.70 [- 2.34; 0.93] (p = 0.15) could be observed in the meta-analysis. In acute pain results vary greatly between studies depending especially on co-medication and timepoints of assessment after surgery. A significant reduction in analgesics or opiate intake was documented in most studies evaluating this effect in chronic and acute pain. In 3 of the 12 randomized controlled trials in patients with chronic pain, a sustainable pain reduction over a period of up to 12months was shown. Overall, aVNS was very well tolerated. This systematic review and meta-analysis indicate that aVNS can be an effective and safe non-drug treatment in patients with specific chronic and acute postoperative pain conditions. Further research is needed to identify the influence of simulation parameters and find optimal and standardized treatment protocols while considering quality-of-life outcome parameters and prolonged follow-up periods. A more standardized approach and harmonization in study designs would improve comparability and robustness of outcomes.

Visual placebo and nocebo effects.

Placebo and nocebo effects modulate symptom perception through expectations and learning processes in various domains. Predominantly, their impact has been investigated on pain and physical performance. However, the influence of placebos and nocebos on visual system functionality has yet to be explored. The present study aimed to test whether placebo and nocebo effects can intervene in altering participants' performance outcomes during a novel visual accuracy task and to examine the underlying neural mechanisms through EEG. After performing a baseline session, visual accuracy was said to be enhanced or disrupted by a sham transcranial electrical stimulation over the occipital lobe. Behavioural results showed a significant increase in visual accuracy for the placebo group, from the baseline session to the test session, whereas the nocebo group showed a decrease in visual accuracy. EEG analyses on the event-related potential P300 component, conducted on both a centro-parietal electrode patch and a parieto-occipital, one displayed an increase in the amplitude of P300 for the placebo group, and a decrease in the nocebo group. These findings suggest for the first time that placebo and nocebo effects can influence visual perception and attentional processes linked to it. Overall, the present study contributes to understanding how expectations affect sensory perception beyond pain and the motor system, paving the way for investigating these phenomena in other sensory modalities such as auditory or olfactory perception. KEY POINTS: Placebo and nocebo effects have been studied predominantly in pain and motor performance fields. In a novel visual task, the impact of placebo and nocebo effects on the visual system has been evaluated, in both early components (stimuli-related) and late components (attention-related). The placebo group showed an increase in visual accuracy and EEG-evoked potential amplitudes, whereas the nocebo group showed a decrease in both. This study shows how expectations and the related placebo and nocebo effects can shape basic stimuli sensory perception in the visual domain.

How distributed subcortical integration of reward and threat may inform subsequent approach-avoidance decisions.

Healthy and successful living involves carefully navigating rewarding and threatening situations by balancing approach and avoidance behaviours. Excessive avoidance to evade potential threats often leads to forfeiting potential rewards. However, little is known about how reward and threat information is integrated neurally to inform approach or avoidance decisions. In this preregistered study, participants (Nbehaviour=31, 17F; NMRI=28, 15F) made approach-avoidance decisions under varying reward (monetary gains) and threat (electrical stimulations) prospects during functional MRI scanning. In contrast to theorized parallel subcortical processing of reward and threat information before cortical integration, Bayesian Multivariate Multilevel analyses revealed subcortical reward and threat integration prior to indicating approach-avoidance decisions. This integration occurred in the ventral striatum, thalamus, and bed nucleus of the stria terminalis (BNST). When reward was low, risk-diminishing avoidance decisions dominated, which was linked to more positive tracking of threat magnitude prior to indicating avoidance than approach decisions across these regions. In contrast, the amygdala exhibited dual sensitivity to reward and threat. While anticipating outcomes of risky approach decisions, we observed positive tracking of threat magnitude within the salience network (dorsal anterior cingulate cortex, thalamus, periaqueductal gray, BNST). Conversely, after risk-diminishing avoidance, characterized by reduced reward prospects, we observed more negative tracking of reward magnitude in the ventromedial prefrontal cortex and ventral striatum. These findings shed light on the temporal dynamics of approach-avoidance decision-making. Importantly, they demonstrate the role of subcortical integration of reward and threat information in balancing approach and avoidance, challenging theories positing predominantly separate subcortical processing prior to cortical integration.Significance statement When deciding whether to approach or avoid situations, our decision-making involves balancing potential rewards and threats. Widespread theories of decision-making in humans propose parallel processing of reward and threat information in subcortical regions, followed by cortical integration. Challenging these notions, we found evidence for dual and integrated processing of reward and threat in subcortical regions during decision-making. In contrast, after decision-making, we observed the expected parallel processing while anticipating decision outcomes. These findings advance our understanding of approach-avoidance decision-making processes, opposing traditional views that segregate brain regions as predominantly reward-sensitive or threat-sensitive, thereby paving the way for a more nuanced perspective that takes into account the stage of decision-making.

A bioabsorbable mechanoelectric fiber as electrical stimulation suture.

In surgical medicine, suturing is the standard treatment for large incisions, yet traditional sutures are limited in functionality. Electrical stimulation is a non-pharmacological therapy that promotes wound healing. In this context, we designed a passive and biodegradable mechanoelectric suture. The suture consists of multi-layer coaxial structure composed of (poly(lactic-co-glycolic acid), polycaprolactone) and magnesium to allow safe degradation. In addition to the excellent mechanical properties, the mechanoelectrical nature of the suture grants the generation of electric fields in response to movement and stretching. This is shown to speed up wound healing by 50% and reduce the risk of infection. This work presents an evolution of the conventional wound closure procedures, using a safe and degradable device ready to be translated into clinical practice.

Deep brain stimulation versus vagus nerve stimulation for the motor function of poststroke hemiplegia: study protocol for a multicentre randomised controlled trial

IntroductionDeep brain stimulation (DBS) and vagus nerve stimulation (VNS) can improve motor function in patients with poststroke hemiplegia. No comparison study exists.Methods and analysisThis is a randomised, double-blind, controlled clinical...

HCN1 hyperpolarization-activated cyclic nucleotide–gated channels enhance evoked GABA release from parvalbumin-positive interneurons

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels generate the cationic Ih current in neurons and regulate the excitability of neuronal networks. The function of HCN channels depends, in part, on their subcellular localization. Of the four HCN isoforms (HCN1-4), HCN1 is strongly expressed in the dendrites of pyramidal neurons (PNs) in hippocampal area CA1 but also in presynaptic terminals of parvalbumin-positive interneurons (PV+ INs), which provide strong inhibitory control over hippocampal activity. Yet, little is known about how HCN1 channels in these cells regulate the evoked release of the inhibitory transmitter GABA from their axon terminals. Here, we used genetic, optogenetic, electrophysiological, and imaging techniques to investigate how the electrophysiological properties of PV+ INs are regulated by HCN1, including how HCN1 activity at presynaptic terminals regulates the release of GABA onto PNs in CA1. We found that application of HCN1 pharmacological blockers reduced the amplitude of the inhibitory postsynaptic potential recorded from CA1 PNs in response to selective optogenetic stimulation of PV+ INs. Homozygous HCN1 knockout mice also show reduced IPSCs in postsynaptic cells. Finally, two-photon imaging using genetically encoded fluorescent calcium indicators revealed that HCN1 blockers reduced the probability that an extracellular electrical stimulating pulse evoked a Ca2+ response in individual PV+ IN presynaptic boutons. Taken together, our results show that HCN1 channels in the axon terminals of PV+ interneurons facilitate GABAergic transmission in the hippocampal CA1 region.

Recruitment of Abdominal and Neck Muscles During Four Different Exercises in Healthy Adults

Background and Purpose: Prolonged mechanical ventilation can greatly increase morbidity and mortality. Diaphragm weakness has been identified as a major contributor for 50% of patients; however, other muscles besides the diaphragm contribute to efficient ventilatory function. The purpose of this study was to compare the change in deoxyhemoglobin (ΔHHb) and muscle oxygen saturation (ΔSmO2) (markers of muscle recruitment) of 3 extra-diaphragmatic muscles across 4 different bed exercises. Methods: Using a pretest–posttest design, healthy participants (n = 18) performed 3 minutes of 30 repetitions of 4 exercises: resisted trunk flexion (TF), resisted neck flexion (NF), expiratory threshold loading (ETL), and neuromuscular electrical stimulation (NMES) of the rectus abdominis and external obliques. Near infrared spectroscopy was used to measure ΔHHb, and ΔSmO2 in the sternocleidomastoid, rectus abdominis, and external obliques during these exercises. Results: Increases of ΔHHb were highest for the sternocleidomastoid during NF and for rectus abdominis and external obliques during TF (P &lt; .010). The opposite pattern was shown for ΔSmO2; decreases of ΔSmO2 were largest for the sternocleidomastoid during NF and for rectus abdominis and external obliques during TF (P &lt; .005). No significant differences were observed in ΔHHb and ΔSmO2 for rectus abdominis and external obliques during ETL versus NF or NMES nor were there differences when comparing NF versus NMES for these 2 muscles. Conclusion: TF and NF are most effective for recruiting abdominal muscles and sternocleidomastoid, respectively, whereas ETL showed a variable response. Stimulation parameters of NMES and its tolerance can limit outcomes.

Secondary Sarcopenia in Patients with Locomotor Disorders: Prevalence, Diagnosis and Medical Rehabilitation. A Review

INTRODUCTION. The development of rehabilitation methods for patients with sarcopenia, a generalized age-associated loss of skeletal muscle mass and strength, is important, since sarcopenia leads to pronounced weakness, functional and motor disorders and an increased risk of death in the elderly. AIM. To analyze the prevalence, features of pathogenesis, diagnosis of secondary sarcopenia, including against the background of motor disorders due to stroke, as well as methods of treatment and medical rehabilitation of such patients. MAIN CONTENT. Among the secondary forms, sarcopenia is of the greatest clinical importance against the background of the consequences of acute cerebrovascular accident (ACA), due to muscular atrophy associated with paralysis and immobility, spasticity, inflammation and denervation of muscles, malnutrition and intestinal absorption of protein and vitamin D. Recent studies show that the prevalence of sarcopenia in stroke patients in emergency hospitals is 8.5–33.8 %, according to other data — more than 42 %. Muscle weakness after a stroke contributes to a decrease in physical functions and the development of disability, and sarcopenia leads to adverse outcomes 90 days after a stroke. According to the meta-analysis, which included 7 cohort studies with a total sample of 1,774 patients who underwent ACA, 27.1 % of them had sarcopenia. Moreover, the presence of sarcopenia negatively affected the clinical and functional outcomes of ACA, as well as the results of medical rehabilitation (odds ratio: 2.42, 95 % confidence interval: 1.76–3.33, p 0.001). CONCLUSION. Despite the prevalence and relevance of this pathology, rehabilitation programs for patients with sarcopenia against the background of the consequences of ACA have not been developed. Isolated foreign publications demonstrate the effectiveness of certain methods of physical therapy and electrical stimulation, but the evidence base for their effectiveness is low.