External Stimulation Research Articles

Rapid rebalancing of co-tuned ensemble activity in the auditory cortex.

Sensory information is represented by small varying neuronal ensembles in sensory cortices. In the auditory cortex (AC) repeated presentations of the same sound activate differing ensembles indicating high trial-by trial variability in activity even though the sounds activate the same percept. Efficient processing of complex acoustic signals requires that these sparsely distributed neuronal ensembles actively interact in order to provide a constant percept. Thus, the differing ensembles might interact to process the incoming sound inputs. Here, we probe interactions within and across ensembles by combining in vivo 2-photon Ca 2+ imaging and holographic optogenetic stimulation to study how increased activity of single cells level affects the cortical network. We stimulated a small number of neurons sharing the same frequency preference alongside the presentation of a target pure tone, further increasing their tone-evoked activity. We found that other non-stimulated co-tuned neurons decreased their tone-evoked activity when the frequency of the presented pure tone matched to their tuning property, while non co-tuned neurons were unaffected. Activity decrease was greater for non-stimulated co-tuned neurons with higher frequency selectivity. Co-tuned and non co-tuned neurons were spatially intermingled. Our results shows that co-tuned ensembles communicated and balanced their total activity across the larger network. The rebalanced network activity due to external stimulation remained constant. These effects suggest that co-tuned ensembles in AC interact and rapidly rebalance their activity to maintain encoding homeostasis, and that the rebalanced network is persistent.

Serial dependencies for externally and self-generated stimuli.

Our senses are constantly exposed to external stimulation. Part of the sensory stimulation is produced by our own movement, like visual motion on the retina or tactile sensations from touch. Sensations caused by our movements appear attenuated. The interpretation of current stimuli is influenced by previous experiences, known as serial dependencies. Here we investigated how sensory attenuation and serial dependencies interact. In Experiment 1, we showed that temporal predictability causes sensory attenuation. In Experiment 2, we isolated temporal predictability in a visuospatial localization task. Attenuated stimuli are influenced by serial dependencies. However, the magnitude of the serial dependence effects varies, with greater effects when the certainty of the previous trial is equal to or greater than the current one. Experiment 3 examined sensory attenuation's influence on serial dependencies. Participants localized a briefly flashed stimulus after pressing a button (self-generated) or without pressing a button (externally generated). Stronger serial dependencies occurred in self-generated trials compared to externally generated ones when presented alternately but not when presented in blocks. We conclude that the relative uncertainty in stimulation between trials determines serial dependency strengths.

276 - Effects of External Neuromuscular Electrical Stimulation in Women with Urgency Urinary Incontinence: A Randomized Sham-Controlled Study

276 - Effects of External Neuromuscular Electrical Stimulation in Women with Urgency Urinary Incontinence: A Randomized Sham-Controlled Study

Photo-thermal and temperature-regulated sodium alginate-g-mPEG/carbon nanotube hybrid fibers with improved tensile strength

Despite the remarkable potential of phase change fibers for energy storage, their practical deployment has been hindered by two crucial challenges: inadequate external thermal stimulation to induce phase transition and leakage of the phase-change material. In this study, we successfully incorporated carbon nanotubes (CNTs) into a solution of sodium alginate grafted polyethylene glycol monomethyl ether (SA-g-mPEG) and utilized wet spinning processing to fabricate CNTs/SA-g-mPEG hybrid fibers with enhanced photo-thermal conversion and robust solid-solid phase change capabilities. Upon exposure to sunlight for merely 60 s, the hybrid fibers achieved a remarkable peak temperature of 40 °C. Upon cessation of sunlight exposure, these fibers demonstrated a gradual release of thermal energy, thereby underlining their exceptional photothermal conversion and temperature regulation capabilities. Furthermore, DSC analysis revealed that, at an optimal grafting ratio of 36.6 %, the hybrid fibers exhibited ΔHc and ΔHm values of 48.23 J/g and 50.83 J/g, respectively. Notably, hybrid fibers with a grafting ratio of 20.2 % demonstrated substantial enhancements in tensile properties, achieving a maximum breaking strength of approximately 2.02 cN/dtex—an impressive 11.3 % increase compared to SA-g-mPEG composite fibers. Our findings suggest that CNTs/SA-g-mPEG hybrid fibers hold immense promise for applications in body heat storage, fabric temperature regulation, and related fields.

Effects of Korean red ginseng on auditory, cognitive, and liver functions in a naturally aged mouse model

BackgroundKorean Red Ginseng and ginsenosides have been studied for their efficacy against various diseases, including those related to aging. However, most aging studies use D-galactose to induce aging, which often does not accurately represent natural aging. This study aimed to verify improvements in auditory, cognitive, and liver function through administering red ginseng to an 18-month-old naturally aging mouse model. MethodsAuditory function was assessed using Auditory Brainstem Response (ABR) and Auditory Middle Latency Response (AMLR). Cognitive function was evaluated electrophysiologically with P300 and mismatch negativity (MMN), and behaviorally using the Y-maze. Additionally, biochemical tests and histological analysis were conducted to assess liver function. The effects of red ginseng on gene expression regulation were also examined in the cochlea, auditory cortex, and liver, focusing on age-related disease processes. ResultsRed ginseng significantly decreased hearing thresholds and improved central auditory function. It also enhanced cognitive behavior and function in response to external stimulation. Furthermore, red ginseng regulated alkaline phosphatase (ALP), albumin (Alb), and total protein (TP) levels, notably decreasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Hematoxylin and eosin (H&E) staining of liver tissue showed significant improvement in fat droplets. These effects appear to be mediated by the regulation of aging-related genes Dec, c-Jun, Stat5b, and Lims2. ConclusionThese results suggest that red ginseng improves auditory, cognitive, and liver functions in a naturally aged mouse model.

Combinatorial responsiveness of single chemosensory neurons to external stimulation of mouse explants revealed by DynamicNeuronTracker.

Calcium fluorescence imaging enables us to investigate how individual neurons of live animals encode sensory input or drive specific behaviors. Extracting and interpreting large-scale neuronal activity from imaging data are crucial steps in harnessing this information. A significant challenge arises from uncorrectable tissue deformation, which disrupts the effectiveness of existing neuron segmentation methods. Here, we propose an open-source software, DynamicNeuronTracker (DyNT), which generates dynamic neuron masks for deforming and/or incompletely registered 3D calcium imaging data using patch-matching iterations. We demonstrate that DyNT accurately tracks densely populated neurons, whereas a widely used static segmentation method often produces erroneous masks. DyNT also includes automated statistical analyses for interpreting neuronal responses to multiple sequential stimuli. We applied DyNT to analyze the responses of pheromone-sensing neurons in mice to controlled stimulation. We found that four bile acids and four sulfated steroids activated 15 subpopulations of sensory neurons with distinct combinatorial response profiles, revealing a strong bias toward detecting sulfated estrogen and pregnanolone.

Metasurface Absorber for Blood Hemoglobin Concentration.

In this study, a biosensing scenario is developed for monitoring blood quality based on the detection of blood hemoglobin concentration. The procedure involves considering the blood sample as the dielectric with different refractive indexes for different concentrations of hemoglobin. Usually, the sensitivity to design parameters is the major issue with the metasurface-based detection. To address this issue, a three-layer graphene-based wave absorber is designed and modeled using passive circuit elements. The major idea behind this work is to maximize the device sensitivity against the blood sample. The research methodology involves impedance matching between the device and the surrounding environment, while full-wave simulation is also performed and compared to ensure circuit view accuracy. The findings suggest that the proposed graphene-based absorber can efficiently monitor blood quality via dual absorption peaks. The simulation results extracted from impedance matching and the full-wave method indicate frequency shifts of the second absorption peak. These shift values are interpreted based on hemoglobin concentration. Additionally, ample analyses are provided to show the reliability of the proposed absorber against geometrical aspects, incident angle, external stimulation, and the graphene electron relaxation time.

Dynamically crosslinked poly(vinyl alcohol)/borax strain sensors for organ motion monitoring

Wearable electronic sensing devices can detect various physiological responses and subtle changes in the skin in real time for the early detection and treatment of potential health problems or diseases. Among them, flexible hydrogel-based sensors are attracting much attention because they can monitor human movements and physiological signals. However, developing hydrogel-based sensors with rapid self-healing, self-adhesion, excellent conductivity and sensitivity characteristics remains a challenge. In this study, a hydrogel with a dynamic reversible network structure was developed using poly(vinyl alcohol) (PVA), hyaluronic acid (HA), borax, and tannic acid (TA). Multiple hydrogen bonds resulting from abundant hydroxyl groups in the hydrogel composed of borax, PVA, and TA improved the self-healing ability of the hydrogel, and the conductivity of this system (∼0.62 S/m) was improved upon immersion in NaCl. The optimum hydrogel exhibited excellent elasticity (∼941 %), biocompatibility, and demonstrated adhesion to porcine skin (dry: 5.3 kPa; wet: 2 kPa) without external stimulation in air and underwater environments. In addition, the fabricated hydrogels exhibited excellent sensitivity (∼300 % strain, gauge factor (GF) = 2.86; 300–900 % strain, GF = 4.95), allowing them to detect and distinguish various large and small human movements. Hydrogels that exhibited stable electrical signals even after 500 cycles were obtained, and the PBHT-N hydrogels were implanted into rabbit hearts to verify their applicability as strain sensors for effective real-time heart rate monitoring during rapid body movement.

Structural Diversity of 2D Molecular Self-Assemblies Arising from Carboxyl Groups Attached to a Molecule: An STM Study at the Liquid-Solid Interface.

Understanding the molecular self-assembly behavior, especially at the microscopic level, sheds light on the rational design of artificial supramolecular systems at surfaces. In this work, scanning tunneling microscopy (STM) and force field simulations were utilized to explore two molecular systems where two and four carboxyl groups are symmetrically modified onto a skeleton. The two target molecules are 4,4'-(ethyne-1,2-diyl) dibenzoic acid (EBA) and 1,1'-ethynebenzene-3,3',5,5,'-tetracarboxylic acid (TCA). The former molecular assembly led to robust close packing, whereas the latter resulted in low-density arrangements that present significant adaption, namely, undergoing phase transformations upon external stimulations, e.g., sensitive to STM-polarity switching and guest molecule incorporations.

A carboxymethyl cellulose/chitosan-based hydrogel harvests robust adhesive, on-demand detachment and self-healing performances for deep burn healing

The irregularities resulting from burns and the discomfort associated with changing dressings during treatment remain challenging to provide effective wound therapy. Hydrogels typically lack the capacity to adhere to tissue and are unable to remain at the wound site for an adequate duration, or fail to detach from tissue when required. In this study, a carboxymethyl cellulose/chitosan-based hydrogel with robust tissue adhesion, self-healing and on-demand detachment was designed via a Schiff-base reaction for deep burn healing. The network structure is self-repairing and does not require external stimulation. The injectable hydrogel fragments undergo self-healing, forming a piece of hydrogel that adapts to the shape of the wound and completely fills the scald wound. The Schiff-base reaction in the hydrogel is formed by the aldehyde group of dialdehyde-modified carboxymethyl cellulose (DCMC) and the amino group of dopamine modified carboxymethyl chitosan (CS-DA), which acts as a dynamic crosslink and endows the hydrogel with self-healing capability and on-demand detachment from tissues by using a benign amino acid solution. Additionally, the incorporation of dopamine has been demonstrated to augment the adhesive properties of the hydrogel. Cytotoxicity assays revealed that the hydrogels exhibit favourable biocompatibility. This research offers a promising approach for the management of burn injuries and represents a significant advancement in the development of cellulose/chitosan hydrogels for biomedical applications.

Engineering exosomes derived from TNF-α preconditioned IPFP-MSCs enhance both yield and therapeutic efficacy for osteoarthritis

BackgroundThe pathogenesis of osteoarthritis (OA) involves the progressive degradation of articular cartilage. Exosomes derived from mesenchymal stem cells (MSC-EXOs) have been shown to mitigate joint pathological injury by attenuating cartilage destruction. Optimization the yield and therapeutic efficacy of exosomes derived from MSCs is crucial for promoting their clinical translation. The preconditioning of MSCs enhances the therapeutic potential of engineered exosomes, offering promising prospects for application by enabling controlled and quantifiable external stimulation. This study aims to address these issues by employing pro-inflammatory preconditioning of MSCs to enhance exosome production and augment their therapeutic efficacy for OA.MethodsThe exosomes were isolated from the supernatant of infrapatellar fat pad (IPFP)-MSCs preconditioned with a pro-inflammatory factor, TNF-α, and their production was subsequently quantified. The exosome secretion-related pathways in IPFP-MSCs were evaluated through high-throughput transcriptome sequencing analysis, q-PCR and western blot analysis before and after TNF-α preconditioning. Furthermore, exosomes derived from TNF-α preconditioned IPFP-MSCs (IPFP-MSC-EXOsTNF−α) were administered intra-articularly in an OA mouse model, and subsequent evaluations were conducted to assess joint pathology and gait alterations. The expression of proteins involved in the maintenance of cartilage homeostasis within the exosomes was determined through proteomic analysis.ResultsThe preconditioning with TNF-α significantly enhanced the exosome secretion of IPFP-MSCs compared to unpreconditioned MSCs. The potential mechanism involved the activation of the PI3K/AKT signaling pathway in IPFP-MSCs by TNF-α precondition, leading to an up-regulation of autophagy-related protein 16 like 1(ATG16L1) levels, which subsequently facilitated exosome secretion. The intra-articular administration of IPFP-MSC-EXOsTNF−α demonstrated superior efficacy in ameliorating pathological changes in the joints of OA mice. The preconditioning of TNF-α enhanced the up-regulation of low-density lipoprotein receptor-related protein 1 (LRP1) levels in IPFP-MSC-EXOsTNF−α, thereby exerting chondroprotective effects.ConclusionTNF-α preconditioning constitutes an effective and promising method for optimizing the therapeutic effects of IPFP-MSCs derived exosomes in the treatment of OA.Graphical

Developing the Attentive Brain: Contribution of Cognitive Neuroscience to a Theory of Attentional Development

Attention is a fundamental cognitive mechanism whose primary function is to regulate and organize the flow of perceptions and actions shaping our mental life. Early cognitive models have highlighted aspects of sustained, selective, and executive control as essential components of attention. These three broad aspects can be further subdivided into subordinate operations, depending on whether the particular function is mostly driven by external stimulation (bottom-up attention) or relies on endogenous processes such as voluntary intentions or expectations (top-down attention). After several decades of cognitive neuroscience research, these different functions have been associated with specific circuits of brain regions. Based on the cognitive neuroscience framework, this paper presents a theory of attention development and discusses behavioral and brain evidence regarding the development of attention function during the first years of life.

Memristors-coupled neuron models with multiple firing patterns and homogeneous and heterogeneous multistability

Abstract Memristors are extensively used to estimate the external electromagnetic stimulation and synapses for neurons. In this paper, two distinct scenarios, i.e., an ideal memristor serves as external electromagnetic stimulation and a locally active memristor serves as a synapse, are formulated to investigate the impact of a memristor on a two-dimensional Hindmarsh–Rose neuron model. Numerical simulations show that the neuronal models in different scenarios have multiple burst firing patterns. The introduction of the memristor makes the neuronal model exhibit complex dynamical behaviors. Finally, the simulation circuit and DSP hardware implementation results validate the physical mechanism, as well as the reliability of the biological neuron model.

Construction and Performance Study of a Dual-Network Hydrogel Dressing Mimicking Skin Pore Drainage for Photothermal Exudate Removal and On-Demand Dissolution.

In recent years, negative pressure wound dressings have garnered widespread attentions. However, it is challenging to drain the accumulated fluid under negative pressures for hydrogel dressings. To address this issue, this study prepared a chemical/physical duel-network PEG-CMCS/AG/MXene hydrogel composed by chemical disulfide crosslinked network of four-arm polyethylene glycol/carboxymethyl chitosan (4-Arm-PEG-SH/CMCS), and the physical network of hydrogen bond of agar (AG). Under near-infrared light (NIR) irradiation, the PEG-CMCS/AG/MXene hydrogel undergoes photothermal heating due to integrate of MXene, which destructs the hydrogen bond network and allows the removal of exudate through a mechanism mimicking the sweat gland-like effect of skin pores. The photothermal heating effect also enables the antimicrobial activity to prevent wound infections. The excellent electrical conductivity of PEG-CMCS/AG/MXene can promote cell proliferation under the external electrical stimulation (ES) in vitro. The animal experiments of full-thickness skin defect model further demonstrate its ability to accelerate wound healing. The conversion between thioester and thiol achieved with L-cysteine methyl ester hydrochloride (L-CME) can provides the on-demand dissolution of the dressing in situ. This study holds promises to provide a novel solution to the issue of fluid accumulations under hydrogel dressings and offers new approaches to alleviating or avoiding the significant secondary injuries caused by frequent dressing changes.

Systematic Experimental Evaluation of Aeroelastic Characteristics of a Highly Flexible Wing Demonstrator

This paper presents a comprehensive experimental analysis of the evolutionary modal characteristics of a highly flexible wing that exhibits bending–torsion coupling-driven instability. By implementing operational modal analysis on responses triggered by a combination of an external pulse-like stimulation and turbulence within the flow, this paper presents the airspeed-driven variations of the modal frequencies, damping ratios, and the underlying modal coupling behavior, leading to instability. This analysis is extended to varying the wing root pitch angles through which the effects of geometrical nonlinearity are exercised. Their effects are particularly noted on the hump feature of the airspeed-driven damping ratio locus of the mode responsible for instability. The decreasing critical damping ratio is shown to result in amplified turbulence-driven responses, which pose significant challenges to identification procedures by masking the visibility of other modes. Furthermore, through a novel technique used to analyze the modal coupling, the relative phase and magnitude properties of the coupled bending–torsion composition of the critical mode before and at flutter onset are evidenced experimentally. It is demonstrated that these relative participation measures provide a strong indication of the response content of the limit cycle oscillations that emerge after the flutter speed.

Genetic patterning in hippocampus of rat undergoing impaired spatial memory induced by long-term heat stress

The organism's normal physiological function is greatly impacted in a febrile environment, leading to the manifestation of pathological conditions including elevated body temperature, dehydration, gastric bleeding, and spermatogenic dysfunction. Numerous lines of evidence indicate that heat stress significantly impacts the brain's structure and function. Previous studies have demonstrated that both animals and humans experience cognitive impairment as a result of exposure to high temperatures. However, there is a lack of research on the effects of prolonged exposure to high-temperature environments on learning and memory function, as well as the underlying molecular regulatory mechanisms. In this study, we examined the impact of long-term heat stress exposure on spatial memory function in rats and conducted transcriptome sequencing analysis of rat hippocampal tissues to identify the crucial molecular targets affected by prolonged heat stress exposure. It was found that the long-term heat stress impaired rats' spatial memory function due to the pathological damages and apoptosis of hippocampal neurons at the CA3 region, which is accompanied with the decrease of growth hormone level in peripheral blood. RNA sequencing analysis revealed the signaling pathways related to positive regulation of external stimulation response and innate immune response were dramatically affected by heat stress. Among the verified differentially expressed genes, the knockdown of Arhgap36 in neuronal cell line HT22 significantly enhances the cell apoptosis, suggesting the impaired spatial memory induced by long-term heat stress may at least partially be mediated by the dysregulation of Arhgap36 in hippocampal neurons. The uncovered relationship between molecular changes in the hippocampus and behavioral alterations induced by long-term heat stress may offer valuable insights for the development of therapeutic targets and protective drugs to enhance memory function in heat-exposed individuals.

Acoustic deep brain modulation: Enhancing neuronal activation and neurogenesis

BackgroundNon-invasive deep brain modulation (DBM) stands as a promising therapeutic avenue to treat brain diseases. Acoustic DBM represents an innovative and targeted approach to modulate the deep brain, employing techniques such as focused ultrasound and shock waves. Despite its potential, the optimal mechanistic parameters, the effect in the brain and behavioral outcomes of acoustic DBM remains poorly understood. ObjectiveTo establish a robust protocol for the shock wave DBM by optimizing its mechanistic profile of external stimulation, and to assess its efficacy in preclinical settings. MethodsWe used shockwaves due to their capacity to leverage a broader spectrum of peak intensity (10–127 W/mm2) in contrast to ultrasound (0.1–5.0 W/mm2), thereby enabling a more extensive range of neuromodulation effects. We established various types of shockwave pressure profiles of DBM and compared neural and behavioral responses. To ascertain the anticipated cause of the heightened neural activity response, numerical analysis was employed to examine the mechanical dynamics within the brain. ResultsAn optimized profile led to an enhancement in neuronal activity within the hypothalamus of mouse models. The optimized profile in the hippocampus elicited a marked increase in neurogenesis without neuronal damage. Behavioral analyses uncovered a noteworthy reduction in locomotion without significant effects on spatial memory function. ConclusionsThe present study provides an optimized shock wave stimulation protocol for non-invasive DBM. Our optimized stimulation profile selectively triggers neural functions in the deep brain. Our protocol paves the way for new non-invasive DBM devices to treat brain diseases.

A water strider-inspired intestinal stent actuator for controllable adhesion and unidirectional biofluid picking

Soft-bodied aquatic organisms exhibit extraordinary navigation and mobility in liquid environments which inspiring the development of biomimetic actuators with complex movements. Stimulus-responsive soft materials including hydrogels and shape-memory polymers are replacing traditional rigid parts that leading to dynamic and responsive soft actuators. In this study, we took inspiration from water strider to develop a biomimetic actuator for targeted stimulation and pH sensing in the gastrointestinal tract. We designed a soft and water-based Janus adhesive hydrogel patch that attaches to specific parts of the intestine and responds to pH changes through external stimulation. The hydrogel patch that forms the belly of the water strider driver incorporates an inverse opal microstructure that enables pH responsive behavior. The hydrogel patch on the water strider's leg uses a sandwich structure of Cu particles to convert light into heat and bend under infrared light to mimic the water strider's leg simulating the efficient and steady movement of the water strider's leg which transporting the biological fluid in one direction. This miniature bionic actuator demonstrates controlled adhesion and unidirectional biofluid delivery capabilities, proving its potential for targeted stimulus response and pH sensing in the gastrointestinal tract, thus opening up new possibilities for medical applications in the growing field of soft actuators.

Enhanced Energy Storage Properties of Highly Polarized BMT-Based Thin Films through the Multiscale Structure Synergistic Regulation Strategy.

For solving the trade-off relationship of the polarization and breakdown electric field, ferroelectric films with high polarization are playing a critical role in energy storage capacitor applications, especially at moderate/low electric fields. In this work, we propose a multiscale structure (including defect, domain, and grain structures) synergetic optimization strategy to optimize the polarization behavior and energy storage performances of BiMg0.5Ti0.5O3 (BMT) ferroelectric films by introducing Sr0.7La0.2TiO3 (SLT) without compromising the breakdown strength. At a moderate electric field of 2917 kV/cm, a high discharge density of 72.2 J/cm3 has been achieved in 0.9BMT-0.1SLT films, together with good frequency, thermal, and cycle stabilities for energy storage. Importantly, the phase difference Δφ is utilized to quantitatively evaluate the polarization switching mobility of the ferroelectric domain/PNRs at an external electric field stimulation. This research demonstrates that a multiscale structure optimization strategy could effectively regulate the energy storage performance, and ecofriendly BMT-based materials are promising candidates for next-generation energy storage capacitors, especially at moderate/low electric fields.

Recent Advances in Nanomaterials for Modulation of Stem Cell Differentiation and Its Therapeutic Applications.

Challenges in directed differentiation and survival limit the clinical use of stem cells despite their promising therapeutic potential in regenerative medicine. Nanotechnology has emerged as a powerful tool to address these challenges and enable precise control over stem cell fate. In particular, nanomaterials can mimic an extracellular matrix and provide specific cues to guide stem cell differentiation and proliferation in the field of nanotechnology. For instance, recent studies have demonstrated that nanostructured surfaces and scaffolds can enhance stem cell lineage commitment modulated by intracellular regulation and external stimulation, such as reactive oxygen species (ROS) scavenging, autophagy, or electrical stimulation. Furthermore, nanoframework-based and upconversion nanoparticles can be used to deliver bioactive molecules, growth factors, and genetic materials to facilitate stem cell differentiation and tissue regeneration. The increasing use of nanostructures in stem cell research has led to the development of new therapeutic approaches. Therefore, this review provides an overview of recent advances in nanomaterials for modulating stem cell differentiation, including metal-, carbon-, and peptide-based strategies. In addition, we highlight the potential of these nano-enabled technologies for clinical applications of stem cell therapy by focusing on improving the differentiation efficiency and therapeutics. We believe that this review will inspire researchers to intensify their efforts and deepen their understanding, thereby accelerating the development of stem cell differentiation modulation, therapeutic applications in the pharmaceutical industry, and stem cell therapeutics.