Stimulation Conditions Research Articles

Extending the understanding of Shannon’s safe stimulation limit for platinum electrodes: biphasic charge-balanced pulse trains in unbuffered saline at pH = 1 to pH = 12

Objective.In neural electrical stimulation, safe stimulation guidelines are essential to deliver efficient treatment while avoiding neural damage and electrode degradation. The widely used Shannon's limit,k, gives conditions on the stimulation parameters to avoid neural damage, however, underlying damage mechanisms are not fully understood. Moreover, the translation from bench testing toin vivoexperiments still presents some challenges, including the increased polarisation observed, which may influence charge-injection mechanisms. In this work, we studied the influence on damage mechanisms of two electrolyte parameters that are differentin vivocompared to usual bench tests: solution pH and electrolyte gelation.Approach.The potential of a platinum macroelectrode was monitored in a three-electrode setup during current-controlled biphasic charge-balanced cathodic-first pulse trains. Maximum anodic and cathodic potential excursions during pulse trains were projected on cyclic voltammograms to infer possible electrochemical reactions.Main results.In unbuffered saline of pH ranging from 1 to 12, the maximum anodic potential was systematically located in the oxide formation region, while the cathodic potential was located the molecular oxygen and oxide reduction region whenkapproached Shannon's damage limit, independent of solution pH. The results support the hypothesis that Shannon's limit corresponds to the beginning of platinum dissolution following repeated cycles of platinum oxidation and reduction, for which the cathodic excursion is a key tipping point. Despite similar potential excursions between solution and gel electrolytes, we found a joint influence of pH and gelation on the cathodic potential alone, while we observed no effect on the anodic potential. We hypothesise that gelation creates a positive feedback loop exacerbating the effects of pH ; however, the extent of that influence needs to be examined further.Significance.This work supports the hypothesis of charge injection mechanisms associated with stimulation-induced damage at platinum electrodes. The validity of a major hypothesis explaining stimulation-induced damage was tested and supported on a range of electrolytes representing potential electrode environments, calling for further characterisation of platinum dissolution during electrical stimulation in various testing conditions.

Stimulation conditions leading to electrical vestibular co-stimulation in cochlear implant users.

The study objective was to investigate the influence of electrical stimulus properties on cervical and ocular vestibular-evoked myogenic potentials to electrical stimulation by cochlear implants (e-cVEMPs, e-oVEMPs). E-VEMPs were recorded in adult Nucleus cochlear implant (CI) patients using electric pulse trains (4 biphasic pulses at 1000 Hz burst rate). Ground path and stimulation electrodes were varied between monopolar stimulation at basal electrode contact E3 (MP1 + 2 E3), monopolar stimulation at apical electrode contact E20 (MP1 + 2 E20), and bipolar transmodiolar stimulation between E3 and E14 (BP E3-E14). The electric pulse train was further varied to 2 pulses at 1000 Hz, 2 pulses at 500 Hz, and a single pulse, in patients with present e-VEMP responses. VEMPs to bone-conducted vibration (BCV) were recorded as reference in all participants. Measurements were conducted in 30 ears of 27 participants (mean age 49.3 years, SD 12.7 years). E-VEMPs were present in 13 ears (43%). 5 of the 13 cases showed e-VEMPs but no BCV evoked VEMPs. Response numbers increased with increasing stimulation levels. The highest response rate of 40% was obtained for MP1 + 2 E3 stimulation. Stimulus variation did not affect response numbers. E-VEMP amplitudes were comparable to BCV-stimulated VEMPs. Latencies were up to 3.1 ms shorter for electric stimulation. Some patients showed e-VEMP thresholds close to or below the electric hearing threshold level. The occurrence of e-VEMPs is dependent on current path and stimulation level. Vestibular co-stimulation by the CI is more likely in patients with high stimulation levels and for monopolar stimulation of basal electrode contacts. 4.

Effects of selective stimulation of apical electrodes on temporal pitch perception by cochlear implant recipients.

This study investigated whether selective apical stimulation improves temporal pitch perception in eight MED-EL cochlear implant recipients and whether any such improvement relates to auditory-nerve survival. Three stimulation conditions differing in the place and width of excitation were evaluated: single-electrode stimulation of (i) the most apical, (ii) a mid-array electrode, and (iii) multi-electrode stimulation of the four most apical electrodes. Stimulation-current-induced non-stimulating electrode voltages were recorded to identify extracochlear electrodes and gauge insertion depth. The pitches of the four most apical electrodes were compared using place-pitch ranking. Rate-pitch ranking was assessed between 80 and 981 pulses per second for the three stimulation conditions, to estimate the "upper limit" of temporal pitch. Single-electrode apical stimulation did not increase the upper limit relative to other conditions. The polarity effect (PE), defined as the difference between thresholds obtained for triphasic pulse trains with their central high-amplitude phase either anodic or cathodic, was obtained to evaluate peripheral neural health. The PE did not differ between apical and mid-array stimulation or correlate with the upper limit. In conclusion, we found no improvement of temporal pitch perception with single-electrode apical stimulation, and discuss possible explanations for this observation.

Physiology-inspired bifocal fronto-parietal tACS for working memory enhancement

Aging populations face significant cognitive challenges, particularly in working memory (WM). Transcranial alternating current stimulation (tACS) offer promising avenues for cognitive enhancement, especially when inspired by brain physiology. This study (NCT04986787) explores the effect of multifocal tACS on WM performance in healthy older adults, focusing on fronto-parietal network modulation. Individualized physiology-inspired tACS applied to the fronto-parietal network was investigated in two blinded cross-over experiments. The first experiment involved monofocal/bifocal theta-tACS to the fronto-parietal network, while in the second experiment cross-frequency theta-gamma interactions between these regions were explored. Participants have done online WM tasks under the stimulation conditions. Network connectivity was assessed via rs-fMRI and multichannel electroencephalography. Prefrontal monofocal theta tACS modestly improved WM accuracy over sham (d = 0.30). Fronto-parietal stimulation enhanced WM task processing speed, with the strongest effects for bifocal in-phase theta tACS (d = 0.41). Cross-frequency stimulations modestly boosted processing speed with or without impairing task accuracy depending on the stimulation protocol. This research adds to the understanding of physiology-inspired brain stimulation for cognitive enhancement in older subjects.

Targeting APT2 improves MAVS palmitoylation and antiviral innate immunity

Innate immunity serves as the primary defense against viral and microbial infections in humans. The precise influence of cellular metabolites, especially fatty acids, on antiviral innate immunity remains largely elusive. Here, through screening a metabolite library, palmitic acid (PA) has been identified as a key modulator of antiviral infections in human cells. Mechanistically, PA induces mitochondrial antiviral signaling protein (MAVS) palmitoylation, aggregation, and subsequent activation, thereby enhancing the innate immune response. The palmitoyl-transferase ZDHHC24 catalyzes MAVS palmitoylation, thereby boosting the TBK1-IRF3-interferon (IFN) pathway, particularly under conditions of PA stimulation or high-fat-diet-fed mouse models, leading to antiviral immune responses. Additionally, APT2 de-palmitoylates MAVS, thus inhibiting antiviral signaling, suggesting that its inhibitors, such as ML349, effectively reverse MAVS activation in response to antiviral infections. These findings underscore the critical role of PA in regulating antiviral innate immunity through MAVS palmitoylation and provide strategies for enhancing PA intake or targeting APT2 for combating viral infections.

Differential Effects of Continuous Theta Burst Stimulation over the Bilateral and Unilateral Cerebellum on Working Memory.

Recent functional MRI studies have implicated the cerebellum in working memory (WM) alongside the prefrontal cortex. Some findings indicate that the right cerebellum is activated during verbal tasks, while the left is engaged during visuospatial tasks, suggesting cerebellar lateralization in WM function. The cerebellum could be a potential target for non-invasive brain stimulation (NIBS) to enhance WM function in cognitive disorders. However, the comprehensive influence of cerebellar lateralization on different types of WM and the effect of stimulation over the unilateral or bilateral cerebellum remain uncertain. This study was to investigate the cerebellum's functional lateralization and its specific impact on various aspects of WM in a causal manner using unilateral or bilateral cerebellar continuous theta burst stimulation (cTBS), a form of inhibitroy NIBS. Twenty-four healthy participants underwent four sessions of cTBS targeting the left, right, or bilateral Crus I of the cerebellum, or a sham condition, in a controlled cross-over design. WM performance was assessed pre- and post-stimulation using neuropsychological tests, including the 3-back task, spatial WM task, and digit span task. Results indicated that cTBS over the bilateral and right cerebellum both led to a greater improvement in 3-back task performance compared to sham stimulation. Additionally, active cTBS over the bilateral cerebellum yielded better performance in the spatial WM task than sham stimulation. However, no significant differences were observed between stimulation conditions for the auditory digit span task. This study may provide novel causal evidence highlighting the specific involvement of the right and bilateral cerebellum in various types of WM. Specifically, the right cerebellum appears crucial for updating and tracking 3-back WM content, while spatial WM processes require the coordinated engagement of both cerebellar hemispheres.

Impact of Stimulation Duration in taVNS-Exploring Multiple Physiological and Cognitive Outcomes.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that modulates the noradrenergic activity of the locus coeruleus (LC). Yet, there is still uncertainty about the most effective stimulation and reliable outcome parameters. In a double blind, sham-controlled study including a sample of healthy young individuals (N = 29), we compared a shorter (3.4 s) and a longer (30 s) stimulation duration and investigated the effects of taVNS (real vs. sham) on saliva samples (alpha amylase and cortisol concentration), pupil (pupillary light reflex and pupil size at rest) and EEG data (alpha and theta activity at rest, ERPs for No-Go signals), and cognitive tasks (Go/No-Go and Stop Signal Tasks). Salivary alpha amylase concentration was significantly increased in the real as compared to sham stimulation for the 30 s stimulation condition. In the 3.4 s stimulation condition, we found prolonged reaction times and increased error rates in the Go/No-Go task and increased maximum acceleration in the pupillary light reflex. For the other outcomes, no significant differences were found. Our results show that prolonged stimulation increases salivary alpha-amylase, which was expected from the functional properties of the LC. The finding of longer response times to short taVNS stimulation was not expected and cannot be explained by an increase in LC activity. We also discuss the difficulties in assessing pupil size as an expression of taVNS-mediated LC functional changes.

Abnormal activation patterns in MT+ during visual motion perception in major depressive disorder.

Previous studies have found that patients with Major Depressive Disorder (MDD) exhibit impaired visual motion perception capabilities, and multi-level abnormalities in the human middle temporal complex (MT+), a key brain area for processing visual motion information. However, the brain activity pattern of MDD patients during the perception of visual motion information is currently unclear. In order to study the effect of depression on the activity and functional connectivity (FC) of MT+ during the perception of visual motion information, we conducted a study combining task-state fMRI and psychophysical paradigm to compare MDD patients and healthy control (HC). Duration threshold was examined through a visual motion perception psychophysical experiment. In addition, a classic block-design grating motion task was utilized for fMRI scanning of 24 MDD patients and 25 HC. The grating moved randomly in one of eight directions. We examined the neural activation under visual stimulation conditions compared to the baseline and FC. Compared to HC group, MDD patients exhibited increased duration threshold. During the task, MDD patients showed decreased beta value and percent signal change in left and right MT+. In the sample comprising MDD and HC, there was a significant negative correlation between beta value in right MT+ and duration threshold. And in MDD group, activation in MT+ were significantly correlated with retardation score. Notably, no such differences in activation were observed in primary visual cortex (V1). Furthermore, when left MT+ served as the seed region, compared to the HC, MDD group showed increased FC with right calcarine fissure and surrounding cortex and decreased FC with left precuneus. Overall, the findings of this study highlight that the visual motion perception function impairment in MDD patients relates to abnormal activation patterns in MT+, and task-related activity are significantly connected to the retardation symptoms of the disease. This not only provides insights into the potential neurobiological mechanisms behind visual motion perception disorder in MDD patients from the aspect of task-related brain activity, but also supports the importance of MT+ as a candidate biomarker region for MDD.

The Effects of Single and Dual Transcranial Direct Current Stimulation on Motor and Cognitive Functions in Male Gymnasts

Background: The better performance of elite athletes than others may be due to their better mental and psychological advantages. Transcranial direct current stimulation (tDCS) is an attractive technique to improve the physical and mental functions in recent years. Objectives: This study aimed to examine the effects of single and dual tDCS of M1 and DLPFC regions on motor and cognitive functions in male gymnasts. Methods: Sixteen male gymnasts (age mean = 21.70 ± 0.66 years) who were selected randomly, exposed to 4 different intervention conditions in 4 separate sessions with a one-week interval between the sessions, including (1) anodal stimulation of the M1 area; (2) anodal stimulation of the left DLPFC area; (3) simultaneous stimulation of M1 and DLPFC areas; (4) sham stimulation. After ensuring the normal distribution using shapiro-whilk test, gathered data were analyzed with two- way repeated measures ANOVA. Results: The results showed that single and dual tDCS of M1 and DLPFC regions had a significant effect on improving bimanual coordination, eye-hand coordination, reaction time, working memory, and selective attention of male gymnasts. Also, considering the observed effect size, the M1& DLPFC stimulation condition had a greater effect than other stimulation conditions. Conclusions: Based on present findings coaches and sports physiologists can improve the performance of their athletes with inclusion single and dual tDCS into their training routines.

High-definition transcranial direct current stimulation of the parietal cortices modulates the neural dynamics underlying verbal working memory.

Verbal working memory (vWM) is an essential limited-capacity cognitive system that spans the fronto-parietal network and utilizes the subprocesses of encoding, maintenance, and retrieval. With the recent widespread use of noninvasive brain stimulation techniques, multiple recent studies have examined whether such stimulation may enhance cognitive abilities such as vWM, but the findings to date remain unclear in terms of both behavior and critical brain regions. In the current study, we applied high-definition direct current stimulation to the left and right parietal cortices of 39 healthy adults in three separate sessions (left anodal, right anodal, and sham). Following stimulation, participants completed a vWM task during high-density magnetoencephalography (MEG). Significant neural responses at the sensor-level were imaged using a beamformer and whole-brain ANOVAs were used to identify the specific neuromodulatory effects of the stimulation conditions on neural responses serving distinct phases of vWM. We found that right stimulation had a faciliatory effect relative to left stimulation and sham on theta oscillations during encoding in the right inferior frontal, while the opposite pattern was observed for left supramarginal regions. Stimulation also had a faciliatory effect on theta in occipital regions and alpha in temporal regions regardless of the laterality of stimulation. In summary, our data suggest that parietal HD-tDCS both facilitates and interferes with neural responses underlying both the encoding and maintenance phases of vWM. Future studies are warranted to determine whether specific tDCS parameters can be tuned to accentuate the facilitation responses and attenuate the interfering aspects.

TDCS-enhanced cognitive training improves attention and alters connectivity in control and somatomotor networks: A triple blind study

BackgroundExecutive dysfunction such as inattention or forgetfulness can lead to disruptions in a person's daily functioning and quality of life. Objective/HypothesisThis triple-blinded randomized clinical trial assessed the efficacy of bifrontal (over the forehead) transcranial direct current stimulation (tDCS) concurrent with cognitive training to improve cognitive performance in a healthy sample. MethodsFifty-eight participants were randomly assigned to one of three stimulation conditions (2 mA left anode–right cathode, 2 mA right anode–left cathode, or sham), which was administered with cognitive training tasks 3x/week over 12 weeks with assessments at baseline, midpoint (6 weeks), and post-training (12 weeks). We assessed cognitive performance, functional connectivity, and the influence of individual differences in training advancement. ResultsForty participants completed training. We found that at midpoint and post, all groups improved significantly on overall cognitive performance. The left anode group's attention & vigilance score improved significantly at post, but the other two groups did not. Greater attention training advancement predicted attention improvement by post, most notably in the left anode group. Finally, within-network connectivity decreased in the control network and increased in the somatomotor network across all groups. ConclusionsThese results suggest that, given cognitive training, the left anode montage is more effective at improving attention than the right anode montage and sham. Future research may focus on the application of the left anode montage during cognitive training to assess its effectiveness in improving cognition in neuropsychiatric disorders.

Attraction is altered via modulation of the medial prefrontal cortex without explicit knowledge.

Previous studies have demonstrated that brain stimulation can alter an individual's physical appearance via dysregulation of the medial prefrontal cortex (MPFC). In this study, we attempted to determine if individuals who receive repetitive transcranial magnetic stimulation (rTMS) delivered to the MPFC were rated as more attractive by others. It has been previously reported that 1 hertz (Hz) (inhibitory) TMS can alter one's facial expressions such that frontal cortex inhibition can increase expressiveness. These alterations, detected by external observation, remain below the level of awareness of the subject itself. In Phase I, subjects (N = 10) received MPFC rTMS and had their photographs taken after each of the five stimulation conditions, in addition to making self-ratings across a number of variables, including attractiveness. In Phase II, participants (N = 430) rated five pictures of each of the Phase 1 individuals on attractiveness. It was found that there were no significant differences in self-assessment following rTMS (Phase I). However, attractiveness ratings differed significantly in Phase II. There was a significant difference found between 10 Hz TMS delivered to the MPFC (p < 0.001), such that individuals were rated as less attractive. Furthermore, 1 Hz TMS to the MPFC increased the number of 'Most Attractive' ratings, while 10Hz TMS decreased the number of 'Most Attractive' ratings (p < 0.001). These results suggest that the MPFC plays a role in attractiveness ratings to others. These data also support research showing that one's appearance can be altered below the level of awareness via rTMS. To our knowledge, this is the first investigation to examine how brain stimulation influences one's attractiveness.

Development and optimization of a diluted whole blood ELISpot assay to test immune function

Sepsis remains a leading cause of death worldwide with no proven immunomodulatory therapies. Stratifying Patient Immune Endotypes in Sepsis (‘SPIES’) is a prospective, multicenter observational study testing the utility of ELISpot as a functional bioassay specifically measuring cytokine-producing cells after stimulation to identify the immunosuppressed endotype, predict clinical outcomes in septic patients, and test potential immune stimulants for clinical development. Most ELISpot protocols call for the isolation of PBMC prior to their inclusion in the assay. In contrast, we developed a diluted whole blood (DWB) ELISpot protocol that has been validated across multiple laboratories. Heparinized whole blood was collected from healthy donors and septic patients and tested under different stimulation conditions to evaluate the impact of blood dilution, stimulant concentration, blood storage, and length of stimulation on ex vivo IFNγ and TNFα production as measured by ELISpot. We demonstrate a dynamic range of whole blood dilutions that give a robust ex vivo cytokine response to stimuli. Additionally, a wide range of stimulant concentrations can be utilized to induce cytokine production. Further modifications demonstrate anticoagulated whole blood can be stored up to 24 h at room temperature without losing significant functionality. Finally, we show ex vivo stimulation can be as brief as 4 h allowing for a substantial decrease in processing time. The data demonstrate the feasibility of using ELISpot to measure the functional capacity of cells within DWB under a variety of stimulation conditions to inform clinicians on the extent of immune dysregulation in septic patients.

The influence of transcranial direct current stimulation to the trigeminal nerve on attention and arousal.

One mechanism by which transcranial direct current stimulation (tDCS) has been proposed to improve attention is by transcutaneous stimulation of cranial nerves, thereby activating the locus coeruleus (LC). Specifically, placement of the electrodes over the frontal bone and mastoid is thought to facilitate current flow across the face as a path of least resistance. The face is innervated by the trigeminal nerve, and the trigeminal nerve is interconnected with the LC. In this study, we tested whether stimulating the trigeminal nerve impacts indices of LC activity and performance on a sustained attention task. We replicated previous research that shows deterioration in task performance, increases in the rate of task-unrelated thoughts, and reduced pupil responses due to time on task irrespective of tDCS condition (sham, anodal, and cathodal stimulation). Importantly, tDCS did not influence pupil dynamics (pretrial or stimulus-evoked), self-reported attention state, nor task performance in active versus sham stimulation conditions. The findings reported here are consistent with theories about arousal centered on a hypothesized link between LC activity indexed by pupil size, task performance, and self-reported attention state but fail to support hypotheses that tDCS over the trigeminal nerve influences indices of LC function.

Redox Regulation of K+ Channel: Role of Thioredoxin.

Significance: Potassium channels regulate the influx and efflux of K+ ions in various cell types that generate and propagate action potential associated with excitation, contraction, and relaxation of various cell types. Although redox active cysteines are critically important for channel activity, the redox regulation of K+ channels by thioredoxin (Trx) has not been systematically reviewed. Recent Advances: Redox regulation of K+ channel is now increasingly recognized as drug targets in the pathological condition of several cardiovascular disease processes. The role of Trx in regulation of these channels and its implication in pathological conditions have not been adequately reviewed. This review specifically focuses on the redox-regulatory role of Trx on K+ channel structure and function in physiological and pathophysiological conditions. Critical Issues: Ion channels, including K+ channel, have been implicated in the functioning of cardiomyocyte excitation-contraction coupling, vascular hyperpolarization, cellular proliferation, and neuronal stimulation in physiological and pathophysiological conditions. Although oxidation-reduction of ion channels is critically important in their function, the role of Trx, redox regulatory protein in regulation of these channels, and its implication in pathological conditions need to be studied to gain further insight into channel function. Future Directions: Future studies need to map all redox regulatory pathways in channel structure and function using novel mouse models and redox proteomic and signal transduction studies, which modulate various currents and altered excitability of relevant cells implicated in a pathological condition. We are yet at infancy of studies related to redox control of various K+ channels and structured and focused studies with novel animal models. Antioxid. Redox Signal. 00, 00-00.

Contact-Electro-Catalysis Through Electret Behavior to Facilitate Electron Transfer.

Contact-electro-catalysis (CEC) usually uses polymer dielectrics as its catalysts under mechanical stimulation conditions, which although has a decent catalytic dye degradation effect still warrants performance improvement. A carrier separation promotion strategy based on an internal electric field by polarization can effectively improve ferroelectric material performance in photocatalysis and piezocatalysis. Therefore, carrier separation as a necessary process of CEC also can be promoted and is largely expected to improve CEC performance theoretically. However, the carrier separation enhancement by the internal electric field strategy has not been achieved in the CEC experiment yet, because of the difficulty of building an internal electric field in an inert polymer dielectric. Herein, a polytetrafluoroethylene (PTFE) dielectric was charged through an electret process, which was believed to establish an internal electric field for CEC catalysts proved by KPFM, XPS, and triboelectric nanogenerator voltage output analysis. The fastest degradation rate of methyl orange reached over 90% at 1.5 h, while the hydroxyl free radical (•OH) yield of the PTFE electret was nearly three times that of the original PTFE. Density functional theory (DFT) calculations verified that the potential barrier of interatomic electron transfer between PTFE and H2O was reduced by 37% under the internal electric field. The electret strategy used herein to optimize the PTFE catalyst provides a base for the use of other general plastics in CEC and facilitates the production of easily prepared, easily recyclable, and inexpensive polymer dielectric catalysts that can promote large-scale pollutant degradation via CEC.

Tape-assisted fabrication method for constructing PDMS membrane-containing culture devices with cyclic radial stretching stimulation.

Advanced in vitro culture systems have emerged as alternatives to animal testing and traditional cell culture methods in biomedical research. Polydimethylsiloxane (PDMS) is frequently used in creating sophisticated culture devices owing to its elastomeric properties, which allow mechanical stretching to simulate physiological movements in cell experiments. We introduce a straightforward method that uses three types of commercial tape-generic, magic and masking-to fabricate PDMS membranes with microscale thicknesses (47.2 µm for generic, 58.1 µm for magic and 89.37 µm for masking) in these devices. These membranes are shaped as the bases of culture wells and can perform cyclic radial movements controlled via a vacuum system. In experiments with A549 cells under three mechanical stimulation conditions, we analysed transcriptional regulators responsive to external mechanical stimuli. Results indicated increased nuclear yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) activity in both confluent and densely packed cells under cyclically mechanical strains (Pearson's coefficient (PC) of 0.59 in confluent and 0.24 in dense cells) compared with static (PC = 0.47 in confluent and 0.13 in dense) and stretched conditions (PC = 0.55 in confluent and 0.20 in dense). This technique offers laboratories without microfabrication capabilities a viable option for exploring cellular behaviour under dynamic mechanical stimulation using PDMS membrane-equipped devices.

Comparison of modulation efficiency between normal and degenerated primate retina.

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

Theoretical investigation of threshold pressure gradient in hydrate-bearing clayey-silty sediments under combined stress and local thermal stimulation conditions

Due to the characteristics of smaller grain size and higher clay mineral content, the threshold pressure gradient (TPG) exists in multi-phase flow within hydrate-bearing clayey-silty sediments (HBCSS), which significantly affects the gas production from hydrate reservoirs. However, multi-phase flow through HBCSS relates to thermal-hydrological-mechanical coupling, leading to the understanding of TPG in HBCSS with complex pore structures and hydrate distribution is unclear. In this study, a theoretical TPG model of HBCSS is developed by considering the combined influences of effective stress, temperature increase, pore structures, hydrate saturation and its growth patterns. The proposed TPG model has been thoroughly validated using available experimental data. Moreover, the parameter sensitivity analysis is conducted based on this derived model, revealing a positive correlation between TPG and both effective stress and temperature increase. While TPG generally increases with higher hydrate saturation when other parameters are held constant, the relationship between TPG and hydrate saturation is non-monotonic. This observation suggests that TPG is impacted not only by hydrate saturation but also by other factors, including hydrate growth patterns and pore structures. The findings of this study establish a theoretical foundation for characterizing the nonlinear flow behavior during hydrate exploitation.

Interactions between arm and leg neuronal circuits following paired cervical and lumbosacral transspinal stimulation in healthy humans.

Transspinal (or transcutaneous spinal cord) stimulation is a promising noninvasive method that may strengthen the intrinsic spinal neural connectivity in neurological disorders. In this study we assessed the effects of cervical transspinal stimulation on the amplitude of leg transspinal evoked potentials (TEPs), and the effects of lumbosacral transspinal stimulation on the amplitude of arm TEPs. Control TEPs were recorded following transspinal stimulation with one cathode electrode placed either on Cervical 3 (21.3 ± 1.7mA) or Thoracic 10 (23.6 ± 16.5mA) vertebrae levels. Associated anodes were placed bilaterally on clavicles or iliac crests. Cervical transspinal conditioning stimulation produced short latency inhibition of TEPs recorded from left soleus (ranging from - 6.11 to -3.87% of control TEP at C-T intervals of -50, -25, -20, -15, -10, 15 ms), right semitendinosus (ranging from - 11.1 to -4.55% of control TEP at C-T intervals of -20, -15, 15 ms), and right vastus lateralis (ranging from - 13.3 to -8.44% of control TEP at C-T intervals of -20 and - 15 ms) (p < 0.05). Lumbosacral transspinal conditioning stimulation produced no significant effects on arm TEPs. We conclude that in the resting state, cervical transspinal stimulation affects the net motor output of leg motoneurons under the experimental conditions used in this study. Further investigations are warranted to determine whether this protocol may reactivate local spinal circuitry after stroke or spinal cord injury and may have a significant effect in synchronization of upper and lower limb muscle synergies during rhythmic activities like locomotion or cycling.