Trains Of Electrical Stimulation Research Articles

893 Psychophysical Pain Encoding in the Cingulate Cortex Predicts Responsiveness of Electrical Stimulation

INTRODUCTION: The anterior cingulate cortex (ACC) plays an important role in pain's cognitive and emotional processing. Prior studies have used deep brain stimulation (DBS) to treat chronic pain, but results have been inconsistent. This may be due to network adaptation over time and variable causes of chronic pain. Identifying patient-specific pain network features may be necessary to determine patients' candidacy for DBS. METHODS: Four patients who underwent intracranial monitoring for epilepsy (stereo-electroencephalography) participated in a pain task. Subjects placed their hand on a device capable of eliciting thermal pain for five seconds and rated their pain. Current-controlled biphasic trains of electrical stimulation were applied to a random subset of trials for each subject. Thermal pain thresholds with and without electrical stimulation were determined. To evaluate whether patients had neural activity susceptible to modulation, generalized linear mixed-effects models assessed the relationship between broadband high-frequency local field potential amplitude within the cingulate cortex (HFA; 70-150 Hz) and the resulting psychophysical pain evaluations. RESULTS: The pain threshold for each patient was determined from the psychometric probability density function. Two patients had a higher pain threshold with stimulation than without, while the others had no difference. We also evaluated the relationship between neural activity and pain responses. We found that patients who responded to stimulation had specific time windows where high-frequency activity was associated with increased pain ratings. CONCLUSIONS: Stimulation of cingulate regions with increased pain-related neural activity was more effective at modulating pain perception than stimulating non-encoding regions. Personalized evaluation of neural activity biomarkers could help identify the best target for stimulation and predict its effectiveness in future studies evaluating DBS.

The first and second phases of the muscle compound action potential in the thumb are differently affected by electrical stimulation trains.

Sarcolemmal membrane excitability is often evaluated by considering the peak-to-peak amplitude of the compound muscle action potential (M wave). However, the first and second M-wave phases represent distinct properties of the muscle action potential, which are differentially affected by sarcolemma properties and other factors such as muscle architecture. Contrasting with previous studies in which voluntary contractions have been used to induce muscle fatigue, we used repeated electrically induced tetanic contractions of the adductor pollicis muscle and assessed the kinetics of M-wave properties during the course of the contractions. Eighteen participants (24 ± 6 yr; means ± SD) underwent 30 electrically evoked tetanic contractions delivered at 30 Hz, each lasting 3 s with 1 s intervals. We recorded the amplitudes of the first and second M-wave phases for each stimulation. During the initial stimulation train, the first and second M-wave phases exhibited distinct kinetics. The first phase amplitude showed a rapid decrease to reach ∼59% of its initial value (P < 0.001), whereas the second phase amplitude displayed an initial transient increase of ∼19% (P = 0.007). Within subsequent trains, both the first and second phase amplitudes consistently decreased as fatigue developed with a reduction during the last train reaching ∼47% of its initial value (P < 0.001). Analyzing the first M wave of each stimulation train unveiled different kinetics for the first and second phases during the initial trains, but these distinctions disappeared as fatigue progressed. These findings underscore the interplay of factors affecting the M wave and emphasize the significance of separately scrutinizing its first and second phases when assessing membrane excitability adjustments during muscle contractions.NEW & NOTEWORTHY Our understanding of how the first and second phases of the compound muscle action potential (M wave) behave during fatigue remains incomplete. Using electrically evoked repeated tetanic contractions of the adductor pollicis, we showed that the first and second phases of the M wave followed distinct kinetics only during the early stages of fatigue development. This suggests that the factors affecting the M-wave first and second phases may change as fatigue develops.

Responsive deep brain stimulation for the treatment of Tourette syndrome.

To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

Reduction and recovery of self-sustained muscle activity after fatiguing plantar flexor contractions.

Persistent inward calcium and sodium currents (PICs) are crucial for initiation and maintenance of motoneuron firing, and thus muscular force. However, there is a lack of data describing the effects of fatiguing exercise on PIC activity in humans. We simultaneously applied tendon vibration and neuromuscular electrical stimulation (VibStim) before and after fatiguing exercise. VibStim induces self-sustained muscle activity that is proposed to result from PIC activation. Twelve men performed 5-s maximal isometric plantar flexor contractions (MVC) with 5-s rests until joint torque was reduced to 70%MVC. VibStim trials consisted of five 2-s trains of neuromuscular electrical stimulation (20 Hz, evoking 10% MVC) of triceps surae with simultaneous Achilles tendon vibration (115 Hz) without voluntary muscle activation. VibStim was applied before (PRE), immediately (POST), 5-min (POST-5), and 10-min (POST-10) after exercise completion. Sustained torque (Tsust) and soleus electromyogram amplitudes (EMG) measured 3 s after VibStim were reduced (Tsust: -59.0%, p<0.001; soleus EMG: -38.4%, p<0.001) but largely recovered by POST-5, and changes in MVC and Tsust were correlated across the four time points (r=0.69; p<0.001). After normalisation to values obtained at the end of the vibration phase to control for changes in fibre-specific force and EMG signal characteristics, decreases in Tsust (-42.9%) and soleus EMG (-22.6%) remained significant and were each correlated with loss and recovery of MVC (r=0.41 and 0.46, respectively). The parallel changes observed in evoked self-sustained muscle activity and force generation capacity provide motivation for future examinations on the potential influence of fatigue-induced PIC changes on motoneuron output.

Effect of epiretinal electrical stimulation on the glial cells in a rabbit retinal eyecup model.

We examined how pulse train electrical stimulation of the inner surface of the rabbit retina effected the resident glial cells. We used a rabbit retinal eyecup preparation model, transparent stimulus electrodes, and optical coherence tomography (OCT). The endfeet of Müller glia processes line the inner limiting membrane (ILM). To examine how epiretinal electrode stimulation affected the Müller glia, we labeled them post stimulation using antibodies against soluble glutamine synthetase (GS). After 5 min 50 Hz pulse train stimulation 30 μm from the surface, the retina was fixed, immunostained for Müller glia, and examined using confocal microscopic reconstruction. Stimulus pulse charge densities between 133-749 μC/cm2/ph were examined. High charge density stimulation (442-749 μC/cm2/ph) caused significant losses in the GS immunofluorescence of the Müller glia endfeet under the electrode. This loss of immunofluorescence was correlated with stimuli causing ILM detachment when measured using OCT. Müller cells show potassium conductances at rest that are blocked by barium ions. Using 30 msec 20 μA stimulus current pulses across the eyecup, the change in transretinal resistance was examined by adding barium to the Ringer. Barium caused little change in the transretinal resistance, suggesting under low charge density stimulus pulse conditions, the Müller cell radial conductance pathway for these stimulus currents was small. To examine how epiretinal electrode stimulation affected the microglia, we used lectin staining 0-4 h post stimulation. After stimulation at high charge densities 749 μC/cm2/ph, the microglia under the electrode appeared rounded, while the local microglia outside the electrode responded to the stimulated retina by process orientation inwards in a ring by 30 min post stimulation. Our study of glial cells in a rabbit eyecup model using transparent electrode imaging suggests that epiretinal electrical stimulation at high pulse charge densities, can injure the Müller and microglia cells lining the inner retinal surface in addition to ganglion cells.

Towards personalized and optimized fitting of cochlear implants.

A cochlear implant (CI) is a neurotechnological device that restores total sensorineural hearing loss. It contains a sophisticated speech processor that analyzes and transforms the acoustic input. It distributes its time-enveloped spectral content to the auditory nerve as electrical pulsed stimulation trains of selected frequency channels on a multi-contact electrode that is surgically inserted in the cochlear duct. This remarkable brain interface enables the deaf to regain hearing and understand speech. However, tuning of the large (>50) number of parameters of the speech processor, so-called "device fitting," is a tedious and complex process, which is mainly carried out in the clinic through 'one-size-fits-all' procedures. Current fitting typically relies on limited and often subjective data that must be collected in limited time. Despite the success of the CI as a hearing-restoration device, variability in speech-recognition scores among users is still very large, and mostly unexplained. The major factors that underly this variability incorporate three levels: (i) variability in auditory-system malfunction of CI-users, (ii) variability in the selectivity of electrode-to-auditory nerve (EL-AN) activation, and (iii) lack of objective perceptual measures to optimize the fitting. We argue that variability in speech recognition can only be alleviated by using objective patient-specific data for an individualized fitting procedure, which incorporates knowledge from all three levels. In this paper, we propose a series of experiments, aimed at collecting a large amount of objective (i.e., quantitative, reproducible, and reliable) data that characterize the three processing levels of the user's auditory system. Machine-learning algorithms that process these data will eventually enable the clinician to derive reliable and personalized characteristics of the user's auditory system, the quality of EL-AN signal transfer, and predictions of the perceptual effects of changes in the current fitting.

Mechanisms involved in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox)-derived reactive oxygen species (ROS) modulation of muscle function in human and dog bladders.

Roles of redox signaling in bladder function is still under investigation. We explored the physiological role of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) in regulating bladder function in humans and dogs. Mucosa-denuded bladder smooth muscle strips obtained from 7 human organ donors and 4 normal dogs were mounted in muscle baths, and trains of electrical field stimulation (EFS) applied for 20 minutes at 90-second intervals. Subsets of strips were incubated with hydrogen peroxide (H2O2), angiotensin II (Ang II; Nox activator), apocynin (inhibitor of Noxs and ROS scavenger), or ZD7155 (specific inhibitor of angiotensin type 1 (AT1) receptor) for 20 minutes in continued EFS trains. Subsets treated with inhibitors were then treated with H2O2 or Ang II. In human and dog bladders, the ROS, H2O2 (100μM), caused contractions and enhanced EFS-induced contractions. Apocynin (100μM) attenuated EFS-induced strip contractions in both species; subsequent treatment with H2O2 restored strip activity. In human bladders, Ang II (1μM) did not enhance EFS-induced contractions yet caused direct strip contractions. In dog bladders, Ang II enhanced both EFS-induced and direct contractions. Ang II also partially restored EFS-induced contractions attenuated by prior apocynin treatment. In both species, treatment with ZD7155 (10μM) inhibited EFS-induced activity; subsequent treatment with Ang II did not restore strip activity. Collectively, these data provide evidence that ROS can modulate bladder function without exogenous stimuli. Since inflammation is associated with oxidative damage, the effects of Ang II on bladder smooth muscle function may have pathologic implications.

The spatio-temporal properties of calcium transients in hippocampal pyramidal neurons in vitro.

The spatio-temporal properties of calcium signals were studied in cultured pyramidal neurons of the hippocampus using two-dimensional fluorescence microscopy and ratiometric dye Fura-2. Depolarization-induced Ca2+ transients revealed an asynchronous delayed increase in free Ca2+ concentration. We found that the level of free resting calcium in the cell nucleus is significantly lower compared to the soma, sub-membrane, and dendritic tree regions. Calcium release from the endoplasmic reticulum under the action of several stimuli (field stimulation, high K+ levels, and caffeine) occurs in all areas studied. Under depolarization, calcium signals developed faster in the dendrites than in other areas, while their amplitude was significantly lower since larger and slower responses inside the soma. The peak value of the calcium response to the application of 10 mM caffeine, ryanodine receptors (RyRs) agonist, does not differ in the sub-membrane zone, central region, and nucleus but significantly decreases in the dendrites. In the presence of caffeine, the delay of Ca2+ signals between various areas under depolarization significantly declined. Thirty percentage of the peak amplitude of Ca2+ transients at prolonged electric field stimulation corresponded to calcium release from the ER store by RyRs, while short-term stimulation did not depend on them. 20 μM dantrolene, RyRs inhibitor, significantly reduces Ca2+ transient under high K+ levels depolarization of the neuron. RyRs-mediated enhancement of the Ca2+ signal is more pronounced in the central part and nucleus compared to the sub-membrane or dendrites regions of the neuron. In summary, using the ratiometric imaging allowed us to obtain additional information about the involvement of RyRs in the intracellular dynamics of Ca2+ signals induced by depolarization or electrical stimulation train, with an underlying change in Ca2+ concentration in various regions of interest in hippocampal pyramidal neurons.

Motor-evoked potentials after focal electrical stimulation predict drug-induced convulsion potentials in rats

Drug-induced convulsions—often caused by the inhibition of GABA receptors and stimulation of glutamate receptors—are difficult to predict in animals. In this study, we attempted to detect the proconvulsant potential using motor-evoked potentials (MEPs) after focal electrical stimulation or upon using a functional observational battery (FOB). Pentylenetetrazole, kainic acid, and pilocarpine were used as convulsion-inducing drugs, and baclofen was used as a negative control. First, each compound was administered to male rats, and the FOB tests were performed. All drugs induced behavioral changes, but no commonality was found. Single electrical stimulation train MEPs were recorded under anesthesia for 60 min (at 5 min intervals) after administration of each drug. A dose-dependent increase in MEPs was observed for each convulsion-inducing drug. Moreover, paired electrical stimulation (conditioned and test) of the cerebral motor cortex was conducted with a 1–15 ms interstimulus interval (ISI), 10 min after administration of the drug. All convulsion-inducing drugs inhibited the short-interval intracortical inhibition (ISI: 3 ms), which may be associated with GABA. Intracortical facilitation (ISI: 11 ms), related to glutamate, was not enhanced by any drug but was inhibited by pilocarpine. Dose correlation was not found in short-interval intracortical inhibition or intracortical facilitation in any drugs. No changes in MEPs were observed after baclofen administration. These results suggest that it is possible to evaluate the convulsion potential and associated mechanisms using MEP, independent of the behavioral changes. The early identification of convulsion potential using this model will lead to more efficient drug development.

MP07-17 MECHANISMS INVOLVED IN NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE (NADPH) OXIDASE (NOX)-DERIVED REACTIVE OXYGEN SPECIES (ROS) MODULATION OF MUSCLE FUNCTION IN HUMAN BLADDERS.

You have accessJournal of UrologyCME1 May 2022MP07-17 MECHANISMS INVOLVED IN NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE (NADPH) OXIDASE (NOX)-DERIVED REACTIVE OXYGEN SPECIES (ROS) MODULATION OF MUSCLE FUNCTION IN HUMAN BLADDERS. Nagat Frara, Dania Giaddui, Alan S. Braverman, Mary F. Barbe, Changhao Wu, and Michael R. Ruggieri Nagat FraraNagat Frara More articles by this author , Dania GiadduiDania Giaddui More articles by this author , Alan S. BravermanAlan S. Braverman More articles by this author , Mary F. BarbeMary F. Barbe More articles by this author , Changhao WuChanghao Wu More articles by this author , and Michael R. RuggieriMichael R. Ruggieri More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002529.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Generation of reactive oxygen species (ROS) by the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) is a highly regulated process that constitutes one of the main redox signaling components. Excessive ROS production may cause oxidative damage to tissue and organ. Although, the role of redox signaling in different pathological processes has been of intense interest, its importance in bladder pathology remains unexplored. This aim was to use ex vivo muscle strip contractility studies to further explore the physiological role of ROS/Nox in regulating bladder function in humans. METHODS: Mucosa-denuded bladder muscle strips were obtained from human organ transplant donors; three males and two females were mounted in muscle baths. The maximal contractile responses to 120 mM potassium chloride were measured. Trains of electrical field stimulation (EFS) of 1 ms pulse duration, 12 V, 8 Hz at 90 s intervals were applied to each strip for about 20 minutes. Then, subsets of strips were incubated with ROS/Nox agonists or antagonists for 20 minutes in continued trains of EFS. Next, same subsets of strips that were treated with antagonists were retreated with agonists and their responses were detected. All responses are expressed in milli Newtons (mN) or as percentages of control. RESULTS: In male and female human bladders, exogenous application of ROS (hydrogen peroxide; H2O2), at the physiological concentration of 100μM, enhanced EFS-induced smooth muscle strip contractions. Apocynin (100μM), the inhibitor of ROS generating enzyme Nox, attenuated intrinsic muscle strip activity. However, treatment with H2O2 brings the EFS-induced muscle activity back to control level. Application of a key Nox activator and a pro-inflammatory peptide angiotensin II (1μM) augmented EFS-induced smooth muscle contractions. Treatment with AT1 receptor specific antagonist ZD7155 (1μM) inhibited EFS-induced activity, while retreatment with angiotensin II after ZD7155 blockade restores muscle activity to control level. CONCLUSIONS: The enhancement of EFS-evoked contractions by H2O2 and the inhibition of these contractions by the Nox inhibitor apocynin demonstrates the functional relevance of ROS in regulating human bladder smooth muscle activity and suggests that endogenous Nox-derived ROS regulates smooth muscle function. The augmentation of contractions by angiotensin II suggests that activation of Nox via a receptor by its ligand can also enhance smooth muscle activity and that the effect of angiotensin II is mediated by AT1, which was further supported by the inhibitory effect of the selective antagonist ZD7155. Collectively, these data provide evidence for the functional significance of Nox-derived ROS in human bladder and that ROS can modulate bladder function without exogenous stimuli. Since, inflammation is an important mechanism associated with oxidative damage, the effects of angiotensin II on bladder smooth muscle function may have significant pathologic implications. Source of Funding: NIA 1R01AG049321-01A1 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e122 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nagat Frara More articles by this author Dania Giaddui More articles by this author Alan S. Braverman More articles by this author Mary F. Barbe More articles by this author Changhao Wu More articles by this author Michael R. Ruggieri More articles by this author Expand All Advertisement PDF DownloadLoading ...

The residence of synaptically released dopamine on D2 autoreceptors.

SUMMARYNeuromodulation mediated by synaptically released endogenous transmitters acting in G-protein-coupled receptors (GPCRs) is slow primarily because of multistep downstream signaling. What is less well understood is the spatial and temporal kinetics of transmitter and receptor interaction. The present work uses the combination of the dopamine sensor, dLight, to detect the spatial release and diffusion of dopamine and a caged form of a D2-dopamine receptor antagonist, CyHQ-sulpiride, to rapidly block the D2 autoreceptors. Photoactivation of the CyHQ-sulpiride blocks receptors in milliseconds such that the time course of dopamine/receptor interaction is mapped onto the downstream signaling. The results show that highly localized release, but not dopamine diffusion, defines the time course of the functional interaction between dopamine and D2 autoreceptors, which determines downstream inhibition.

Direct and indirect methods to optimize the muscular force response to a pulse train of electrical stimulation

Recent force-fatigue mathematical models in biomechanics [7] allow to predict the muscular force response to functional electrical stimulation (FES) and leads to the optimal control problem of maximizing the force. The stimulations are Dirac pulses and the control parameters are the pulses amplitudes and times of application, the number of pulses is physically limited and the model leads to a sampled data control problem. The aim of this article is to present and compare two methods. The first method is a direct optimization scheme where a further refined numerical discretization is applied on the dynamics. The second method is an indirect scheme: first-order Pontryagin type necessary conditions are derived and used to compute the optimal sampling times.

Effect of oral rehydration solution versus spring water intake during exercise in the heat on muscle cramp susceptibility of young men

BackgroundMuscle cramp is a painful, involuntary muscle contraction, and that occurs during or following exercise is referred to as exercise-associated muscle cramp (EAMC). The causes of EAMC are likely to be multifactorial, but dehydration and electrolytes deficits are considered to be factors. This study tested the hypothesis that post-exercise muscle cramp susceptibility would be increased with spring water ingestion, but reduced with oral rehydration solution (ORS) ingestion during exercise.MethodsTen men performed downhill running (DHR) in the heat (35–36 °C) for 40–60 min to reduce 1.5–2% of their body mass in two conditions (spring water vs ORS) in a cross-over design. The body mass was measured at 20 min and every 10 min thereafter during DHR, and 30 min post-DHR. The participants ingested either spring water or ORS for the body mass loss in each period. The two conditions were counter-balanced among the participants and separated by a week. Calf muscle cramp susceptibility was assessed by a threshold frequency (TF) of an electrical train stimulation to induce cramp before, immediately after, 30 and 65 min post-DHR. Blood samples were taken before, immediately after and 65 min after DHR to measure serum sodium, potassium, magnesium and chroride concentrations, hematocrit (Hct), hemoglobin (Hb), and serum osmolarity. Changes in these varaibles over time were compared between conditions by two-way repeated measures of analysis of variance.ResultsThe average (±SD) baseline TF (25.6 ± 0.7 Hz) was the same between conditions. TF decreased 3.8 ± 2.7 to 4.5 ± 1.7 Hz from the baseline value immediately to 65 min post-DHR for the spring water condition, but increased 6.5 ± 4.9 to 13.6 ± 6.0 Hz in the same time period for the ORS condition (P < 0.05). Hct and Hb did not change significantly (P > 0.05) for both conditions, but osmolarity decreased (P < 0.05) only for the spring water condition. Serum sodium and chloride concentrations decreased (< 2%) at immediately post-DHR for the spring water condition only (P < 0.05).ConclusionsThese results suggest that ORS intake during exercise decreased muscle cramp susceptibility. It was concluded that ingesting ORS appeared to be effective for preventing EAMC.

Effects of transcranial direct current stimulation on electrical train stimulation of the retina

Effects of transcranial direct current stimulation on electrical train stimulation of the retina

Object Shape and Surface Topology Recognition Using Tactile Feedback Evoked through Transcutaneous Nerve Stimulation.

Tactile feedback is critical for distinguishing different object properties. In this article, we determined if tactile feedback evoked by transcutaneous nerve stimulation can be used to detect objects of different shape and surface topology. To evoke tactile sensation at different fingers, a 2x8 electrode grid was placed along the subject's upper arm, and two concurrent electrical stimulation trains targeted the median and ulnar nerve bundles, which evoked individually modulated sensations at different fingers. Fingertip forces of the prosthetic hand were transformed to stimulation current amplitude. Object shape was encoded based on finger-object contact timing. Surface topology represented by ridge height and spacing was encoded through current amplitude and stimulation time interval, respectively. The elicited sensation allowed subjects to determine object shape with success rates >84%. Surface topology recognition resulted in success rates >81%. Our findings suggest that tactile feedback evoked from transcutaneous nerve stimulation allows the recognition of object shape and surface topology. The ability to recognize these properties may help improve object manipulation and promote fine control of a prosthetic hand.

Analysis of electro-mechanical relationship in human iPS cell-derived cardiomyocytes sheets under proarrhythmic condition assessed by simultaneous field potential and motion vector recordings

We investigated the electro-mechanical relationship of human iPS cell-derived cardiomyocyte sheets under arrhythmic condition, which was induced by digitalis intoxication along with the electrical train stimulation (n = 4). We adopted motion vector analysis by high-speed video microscopy and extracellular field potential recording by 64-microelectrode array system. The motion vector analysis uncovered local contractile events at resting phase, at which the field potential analysis showed no deflection in any cell sheet. Thus, motion vector analysis may provide supplemental information over field potential recording in detecting Ca2+-triggered arrhythmias, which may become a new strategy for assessing arrhythmic liability of test articles.

Water intake after dehydration makes muscles more susceptible to cramp but electrolytes reverse that effect

ObjectiveNo previous study has compared water and oral rehydration solution (ORS) intake after dehydration induced by exercise in the heat for the effect on muscle cramps. The present study tested...

Neuronal Development and Onset of Electrical Activity in the Human Enteric Nervous System

The enteric nervous system (ENS) is the largest branch of the peripheral nervous system, comprising complex networks of neurons and glia, which are present throughout the gastrointestinal tract. Although development of a fully functional ENS is required for gastrointestinal motility, little is known about the ontogeny of ENS function in humans. We studied the development of neuronal subtypes and the emergence of evoked electrical activity in the developing human ENS. Human fetal gut samples (obtained via the MRC-Wellcome Trust Human Developmental Biology Resource-UK) were characterized by immunohistochemistry, calcium imaging, RNA sequencing, and quantitative real-time polymerase chain reaction analyses. Human fetal colon samples have dense neuronal networks at the level of the myenteric plexus by embryonic week (EW) 12, with expression of excitatory neurotransmitter and synaptic markers. By contrast, markers of inhibitory neurotransmitters were not observed until EW14. Electrical train stimulation of internodal strands did not evoke activity in the ENS of EW12 or EW14 tissues. However, compound calcium activation was observed at EW16, which was blocked by the addition of 1 μmol/L tetrodotoxin. Expression analyses showed that this activity was coincident with increases in expression of genes encoding proteins involved in neurotransmission and action potential generation. In analyses of human fetal intestinal samples, we followed development of neuronal diversity, electrical excitability, and network formation in the ENS. These processes are required to establish the functional enteric circuitry. Further studies could increase our understanding of the pathogenesis of a range of congenital enteric neuropathies.

The Single Word Auditory Comprehension (SWAC) test: A simple method to identify receptive language areas with electrical stimulation

ObjectivesResective surgery for medically refractory epilepsy in proximity to speech receptive areas requires balancing adequate resection of the epileptogenic zone for optimal seizure control with preservation of function. We develop a simple test (Single Word Auditory Comprehension or SWAC) to localize speech receptive areas by evaluating patients' ability to comprehend a single word. MethodsPatients were studied during presurgical or intraoperative assessment for epilepsy with intracranial electrodes. They were asked to listen to a common word (target word) and to describe what it meant without saying the target word. Electrical stimulation (trains of biphasic 2-ms pulses, 50 Hz for 3 s) was delivered while the patient listened to the target word, not while the patient explained the meaning of the word. In six patients, SWAC test was carried out during extraoperative chronic recordings, and in one patient in the operating theater under local anesthesia. ResultsAmong the 7 patients where the test identified deficits, 6 underwent resection (4 temporal, 1 supramarginal, and 1 occipital). Two patients showed temporary minor speech deficits after resection. No patient showed permanent speech deficits after resection. Conclusion/significanceThe SWAC test is reliable, simple and fast to implement, and suitable for intraoperating mapping. It could be used as a simple initial test to identify receptive language areas where more complex additional tests can be performed.

Effect of hypercapnia on self-sustained muscle activity

The aim of the present study was to determine the effect of hypercapnia on motor neuromuscular activity of the human triceps surae muscle. Nine subjects participated in trials in a normal breathing condition and a CO2 rebreathing condition. In both conditions, in order to provoke self-sustained muscle activity, percutaneous electrical train stimulation was applied to the tibial nerve while each subject lay on a bed. Self-sustained muscle activity, which is an indirect observation of plateau potentials in spinal motoneurons, was measured for 30 s after the train stimulation by using surface electromyography. The sustained muscle activity was increased by CO2 rebreathing (P < 0.05). This finding suggests that motor neuromuscular activity may be linked to the respiratory system that is activated during hypercapnia.