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Vagus nerve stimulation (VNS) is a widely used neuromodulation technique that is currently used or being investigated as therapy for a wide array of human diseases such as epilepsy, depression, Alzheimer’s disease, tinnitus, inflammatory diseases, pain, heart failure and many others. Here, we report a pronounced decrease in brain and core temperature during VNS in freely moving rats. Two hours of rapid cycle VNS (7s on/18s off) decreased brain temperature by around $3^{\circ }$C, while standard cycle VNS (30s on/300s off) was associated with a decrease of around $1^{\circ }$C. Rectal temperature similarly decreased by more than $3^{\circ }$C during rapid cycle VNS. The hypothermic effect triggered by VNS was further associated with a vasodilation response in the tail, which reflects an active heat release mechanism. Despite previous evidence indicating an important role of the locus coeruleus-noradrenergic system in therapeutic effects of VNS, lesioning this system with the noradrenergic neurotoxin DSP-4 did not attenuate the hypothermic effect. Since body and brain temperature affect most physiological processes, this finding is of substantial importance for interpretation of several previously published VNS studies and for the future direction of research in the field.

AIM. Vagus nerve stimulation (VNS) modulates hippocampal dentate gyrus (DG) electrophysiology and induces hypothermia in freely moving rats. This study evaluated whether hippocampal (CA1) electrophysiology is similarly modulated and to what extent this is associated with VNS-induced hypothermia. METHODS. Six freely moving rats received a first 4h session of rapid cycling VNS (7s on/18s off), while CA1 evoked potentials, EEG and core temperature were recorded. In a second 4h session, external heating was applied during the 3rd and 4thh of VNS counteracting VNS-induced hypothermia. RESULTS. VNS decreased the slope of the field excitatory postsynaptic potential (fEPSP), increased the population spike (PS) amplitude and latency, decreased theta (4–12Hz) and gamma (30–100Hz) band power and theta peak frequency. Normalizing body temperature during VNS through external heating abolished the effects completely for fEPSP slope, PS latency and gamma band power, partially for theta band power and theta peak frequency and inverted the effect on PS amplitude. CONCLUSIONS. Rapid cycle VNS modulates CA1 electrophysiology similarly to DG, suggesting a wide-spread VNS-induced effect on hippocampal electrophysiology. Normalizing core temperature elucidated that VNS-induced hypothermia directly influences several electrophysiological parameters but also masks a VNS-induced reduction in neuronal excitability.

Astragaloside IV (AS-IV) is one of the active ingredients in Astragalus membrananceus (Huangqi), a traditional Chinese medicine. The present study investigated the effects of AS-IV on Ca${}^{2+}$ handling in cardiac myocytes to elucidate its possible mechanism in the treatment of cardiac disease. The results showed that AS-IV at 1 and 10$\mu$M reduced KCl-induced [Ca${}^{2+}$]_i increase ($F∕F_0)$ from 1.33$\pm$0.04 (control, $n=$ 28) to 1.22$\pm$0.02 ($P<0.05$, $n=$ 29) and 1.22$\pm$0.02 ($P<$ 0.01, $n=20$), but it enhanced Ca${}^{2+}$ release from SR ($F∕F_0)$ from 1.04$\pm$0.01 (control, $n=30$) to 1.44$\pm$0.03 ($P<0.01$, $n=33$) and 1.60$\pm$0.04 ($P<$ 0.01, $n=3$0), in H9c2 cells. Similar results were obtained in native cardiomyocytes. AS-IV at 1 and 10$\mu$M inhibited L-type Ca${}^{2+}$ current ($I_{\mathrm{\text{CaL}}})$ from $-$4.42$\pm$0.58 pA/pF of control to $-$2.25$\pm$0.12 pA/pF ($P<$ 0.01, $n=$ 5) and $-$1.78$\pm$0.28 pA/pF ($P<$ 0.01, $n=$ 5) respectively, when the interference of [Ca${}^{2+}$]_i was eliminated due to the depletion of SR Ca${}^{2+}$ store by thapsigargin, an inhibitor of Ca${}^{2+}$ ATPase. Moreover, when BAPTA, a rapid Ca${}^{2+}$ chelator, was used, CDI (Ca${}^{2+}$-dependent inactivation) of $I_{\mathrm{\text{CaL}}}$ was eliminated, and the inhibitory effects of AS-IV on I_CaL were significantly reduced at the same time. These results suggest that AS-IV affects Ca${}^{2+}$ homeostasis through two opposite pathways: inhibition of Ca${}^{2+}$ influx through L-type Ca${}^{2+}$ channel, and promotion of Ca${}^{2+}$ release from SR.

We follow a formal homogenization approach to investigate the effects of mechanical deformations in electrophysiology models relying on a bidomain description of ionic motion at the microscopic level. To that purpose, we extend these microscopic equations to take into account the mechanical deformations, and proceed by recasting the problem in the framework of classical two-scale homogenization in periodic media, and identifying the equations satisfied by the first coefficients in the formal expansions. The homogenized equations reveal some interesting effects related to the microstructure — and associated with a specific cell problem to be solved to obtain the macroscopic conductivity tensors — in which mechanical deformations play a nontrivial role, i.e. they do not simply lead to a standard bidomain problem posed in the deformed configuration. We then present detailed numerical illustrations of the homogenized model with coupled cardiac electrical–mechanical simulations — all the way to ECG simulations — albeit without taking into account the abundantly-investigated effect of mechanical deformations in ionic models, in order to focus here on other effects. And in fact our numerical results indicate that these other effects are numerically of a comparable order, and therefore cannot be disregarded.

The advent of multiple electrodes surface recording during the seventies has contributed importantly to improve our understanding of ventricular tachycardias (VT) mechanisms [1–7]. It has been also used to localise the arrhythmogenic substratum during open-chest surgery [8–11]. In the typical setting used at Sacré-Coeur Hospital [2], unipolar signals are collected by a set of electrodes positioned both on the epicardial surface (63 to 127 leads fixed to a sock pulled over the heart) and on the endocardial surface of the left ventricule (64 to 127 leads fixed on a balloon which is introduced through the mitral valve and inflated).

During the surgery, long sequences of VT induced by burst pacing (driving at a fixed frequency, followed by a discharge of premature stimuli) are recorded. In the standard procedure, a few beats are selected for analysis. The activation times are determined for each electrode. They should correspond to the moments where an electrical front of activation travels through the tissue beneath the electrode. From these, isochronal maps are constructed describing the spatial propagation of the activation. In this analysis, many details of possible clinical relevance may be disregarded concerning the spatiotemporal evolution and the global features of the VT's.

This paper presents some approaches to analyse globally protracted VT episodes. The first section describes some methods to speed up the determination of the activation times. The second section shows how principal component analysis [12] can be used to extract global features of the activation sequences.

Purpose: This study was aimed to investigate the presence of dysphagia with multidimensional objective tests in FM female patients with and without dysphagia symptom compared to healthy female subjects.

Methods: A case control study was conducted on 165 subjects (21 FM patients with dysphagia symptom, 62 FM patients without dysphagia symptom and 82 healthy subjects). All subjects were evaluated with a clinical screening test, endoscopy, electrophysiology of swallowing (dysphagia limit and swallowing intervals) and musculoskeletal ultrasound (cross-sectional thickness and area of swallowing muscles). Patients (with and without dysphagia symptom) and healthy subjects were compared in terms of all evaluation parameters.

Results: The mean age of 165 subjects was $49.86\pm 12.18$ years and all subjects ($n=165$, 100%) were female. Endoscopic evaluation results were similar among three groups ($p=1.000$). Both the functional evaluation of swallowing measured by swallowing intervals ($p$-value between 0.001 and 0.004) and the structural features assessed by the ultrasound ($p$-value between 0.001 and 0.007) were significantly impaired in patient groups compared to healthy subjects. FM patients without dysphagia symptom also had significant impairments in function ($p$-value between 0.001 and 0.004 for swallowing intervals) and structural features ($p$-value between 0.001 and 0.007 for cross-sectional thickness and area of swallowing muscles) compared to healthy subjects.

Conclusion: The structure and function of swallowing may be affected in patients with FM, even without dysphagia symptoms.

Hereditary motor and sensory neuropathy type V (HMSN V) is a rare disorder characterized by the clinical features of spastic paraplegia with peroneal muscular atrophy. A patient with progressive deformity of the feet due to HMSN V underwent clinical, electrophysiological, histopathological examinations, and surgical treatments. Physical examination revealed bilateral pes equinovarus and peroneal muscular atrophy with pyramidal tract features. In the lower limbs, motor nerve conduction velocity could not be determined, and sensory nerve conduction velocity was decreased. In contrast, the results of both the conduction studies were normal for the upper limbs. A sural nerve biopsy revealed a decrease in the number of myelinated fibers and in the diameter of the unmyelinated fibers, and axonal and myelin regeneration was found on light and electron microscopic examinations, suggesting an axonopathy. Since the patient had pyramidal tract features, the same pathological changes may be present in the spinal cord. In the surgical treatment to correct deformity of the feet in this patient, triple arthrodesis was necessary.

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Human heart is elegantly articulated to mechanically contract in response to electrical excitation. Cardiac electrical activity may be described as a multiscale process from sub-cellular to cellular to tissue level. Ion movement at the cellular level through ion channels results in an action potential that propagates as an electrical wave in tissue. A first-principles-based mathematical description of the cellular-level dynamics of cardiac electrophysiological behavior provides a better understanding of the functioning of the heart.

The mathematical models describing cellular dynamics often involve a coupled system of ordinary differential equations (ODEs) with variables including transmembrane voltage, ion concentrations and ion channel gating variables, whose evolution describes activation/inactivation of ion channels. In this study we discuss a mathematical model of the human ventricular myocyte (O’Hara–Rudy model), defined as a system of 41 ODEs, with variables involving membrane voltage, 29 gating variables describing activation of Na${}^{+}$, K${}^{+}$, Ca${}^{2+}$ channels, 11 variables describing ion concentrations and Ca${}^{2+}$ related flux. Runge–Kutta method with variable order and variable time step was adopted to solve the system numerically. We discuss the action potential (AP) profile of a healthy human ventricular myocyte and corresponding dominant ionic currents. We present a phase plot that describes the change in voltage and its rate as the system evolves over time. The phase plot seems to provide more details of the underlying events than the AP curve.

The role of cotransmission by α-amino-3-hydroxy-5-methyl-4-isoxalose propionic acid (AMPA), L-aspartate, N-methyl-D-aspartate (NMDA), and acetylcholine (ACh) as well as the coexpression of AMPA, NMDA, and nicotinic ACh (nACh) receptors on the electrophysiological activity of the primary sensory (AH) and motor (S) neurons of the enteric nervous system are numerically assessed. Results of computer simulations showed that AMPA and L-Asp alone can induce fast action potentials of short duration on AH and S neurons. Costimulation of nACh and AMPA receptors on the soma of the S neuron resulted in periodic spiking activity. A characteristic biphasic response was recorded from the AH neuron after coactivation of AMPA and NMDA receptors. Glutamate alone acting on NMDA receptors caused prolonged depolarization of the AH neuron and failed to depolarize the S neuron. Cojoint stimulation of the AMPA or nACh receptors was required to produce the effect of glutamate. The overall electrical response of neurons to the activation of NMDA receptors was long-term depolarization. Acetylcholine, AMPA, and glutamate acting alone or cojointly enhanced phasic contraction of the longitudinal smooth muscle. Treatment of neurons with AMPA, NMDA, and nACh receptor antagonists revealed intricate properties of the AH and S neurons. Application of MK-801, D-AP5, and CPP reduced the excitability of the AH neuron and totally abolished electrical activity in the S neuron. The information gained into the cotransmission by excitatory amino acids and acetylcholine in the enteric nervous system may be beneficial in the development of novel effective therapeutics to treat diseases associated with altered visceral nociception, i.e. irritable bowel syndrome.

Accurate positioning of endocardial catheters inside cardiovascular structures is crucial in electrophysiology (EP) procedures. Improvements in cardiac mapping are required for a better understanding and treatment of arrhythmias. The proposed Electroloc system is a simple, fast and accurate method for endocardial catheters localization. The key features of Electroloc are the use of conventional EP catheters and the simple data processing for providing localization. Electroloc is able to locate any conventional EP mapping catheter with respect to a noncontact EP catheter used as reference, by sequentially passing a sub-threshold current between the mapping electrode (ME) of the mapping catheter and each electrode of the reference catheter. This creates different potential gradients across the reference catheter used to compute two spatial coordinates (horizontal and vertical coordinates) intended for positioning the ME in the cardiac chamber. In vitro experiments demonstrated that Electroloc is a reliable and sensitive system for localizing the ME with a spatial resolution of 2 mm in the vertical localization and of 5 mm in the horizontal localization. Further studies will be required to improve Electroloc accuracy and to extend its sensitivity range.

Ionic currents across neuron and glial cells membranes lie at the origin of the entire brain electrophysiology. They are the common root of functional brain dynamics and mesoscopic or macroscopic phenomena such as extracellular fields. In particular, they provide the relevant basis to relate cellular electrophysiology and macroscopic dipole models. In order to derive robust features and to envision the multi-scale approaches required to connect the different levels of observation, an essential prerequisite is to have minimal model of elementary ionic motions. In this paper, we propose a general cellular automata framework allowing to investigate the distribution of ionic currents in heterogeneous media interspersed with membranes, from which follows the local electromagnetic field.

The present study sought to determine a profile of integrated behavioral, brain and autonomic alterations in PTSD. Previous findings suggest that PTSD is associated with changes across electrophysiological (EEG and ERP), autonomic and cognitive/behavioral measures. In particular, PTSD has been associated with reduced cognitive performance, altered cortical arousal (measured by EEG), diminished late ERP component to oddball task targets (reduced P3 amplitude) and increased autonomic arousal relative to healthy controls. The present study examined measures of cognitive function, auditory oddball ERP components, autonomic function (heart rate and skin conductance) and EEG during resting conditions in 44 individuals with PTSD and 44 non-trauma-exposed controls, and predicted that an integrated profile of changes across a number of these measures would show a high level of sensitivity and specificity in discriminating PTSD from controls. Nine variables showing strongly significant (p < 0.002) between-group differences were entered into a discriminant function analysis. Four of these measures successfully discriminated the PTSD and non-PTSD groups: change in tonic arousal, duration of attention switching, working memory reaction time and errors of commission during visuospatial maze learning. Tonic arousal change contributed the most variance in predicting group membership. These results extend previous findings and provide an integrated biomarker profile that characterizes both PTSD and non-PTSD groups with a high degree of sensitivity and specificity. This outcome provides a platform for future studies to test how this profile of disturbances in autonomic and information processing may be unique to PTSD or may occur generically across clinical and/or other anxiety disorders.

Using a standardized database of EEG data, recorded during the habituation and oddball paradigms, changes in the auditory event-related potential (ERP) are demonstrated on the time scale of seconds and minutes. Based on previous research and a mathematical model of neural activity, neural mechanisms that could account for these changes are proposed. When the stimulus tones are not relevant to a task, N100 magnitude decreases substantially for the first repetition of a stimulus pattern and increases in response to a variant tone. It is argued these short-term changes are consistent with the hypothesis that there is a refractory period in the neural elements underlying the ERP. In the oddball paradigm, when the stimulus tones are task-relevant, the magnitudes of both N100 and P200 for backgrounds decrease over the entire six-minute recording session. It is argued that these changes are mediated by a decreasing arousal level, and consistent with this, a subject's electrodermal activity (EDA) is shown to reduce over the recording session. By fitting ERPs generated by a biophysical model of neural activity, it is shown that the changes in the background ERPs over the recording session can be reproduced by changing the strength of connections between populations of cortical neurons. For ERPs elicited by infrequent stimuli, there is no corresponding trend in the magnitudes of N100 or P300 components. The effects of stimuli serial order on ERPs are also assessed, showing that the N100 for background ERPs and the N100 and P300 for target ERPs increases as the probability, and expectancy, of receiving a task relevant stimulus increases. Cortical neuromodulation by acetylcholine (ACh) is proposed as a candidate mechanism to mediate the ERP changes associated with attention and arousal.

Cortical spreading depression (CSD) is a wave of neuronal and glial depolarization that propagates across the cortex at a rate of 2–5 mm/min accompanied by reversible electroencephalogram (EEG) suppression, a negative shift of direct current (DC) potential, and change of optical intrinsic signals (OIS). Propagation velocity of CSD is an important parameter used to study this phenomenon. It is commonly determined in an electrophysiological way that measures the time required for a CSD wave to pass along two electrodes. Since the electrophysiology technique fails to reveal the spreading pattern of CSD, velocity calculated in this manner might be inaccurate. In this study, we combined the electrophysiological recording and OIS imaging (OISI) for detecting changes in DC potential and OIS during CSD simultaneously. An optical method based on OISI to determine the CSD velocity, which is measured by generating a series of regions of interest (ROI) perpendicular to the advancing wavefront along propagation direction of CSD at different time points and then dividing by the distance between ROIs over time, is presented. Comparison of the accuracy of the two approaches in determining the CSD velocity is made as well. The average rate of 33 CSDs is 3.52 ± 0.87 mm/min by use of the optical method and 4.36 ± 1.65 mm/min by use of the electrophysiological method. Because of the information about spreading pattern of CSD provided optically, the velocity determined by OISI is of smaller deviation and higher accuracy.

Background: The aim of this study is to determine the prevalence of Martin-Gruber Anastomosis (MGA) in healthy Egyptian subjects, and to discuss the available literature regarding MGA subtypes and their clinical implications.

Methods: An electrophysiological study was conducted in both forearms of 140 healthy subjects. This included the ulnar and median nerves. Compound muscle action potentials were recorded from abductor pollicis brevis, abductor digiti minimi, and first dorsal interosseous muscles. Other measurements included the compound motor action potential amplitude and its innervation ratio.

Results: MGA was found in 56 of the 280 forearms. This included 20 men and 36 women. Type II MGA subtype was the most frequent in both genders. The MGA was bilateral in 6 subjects and more frequent on the right side. The highest mean amplitude and innervation ratio were recorded at first dorsal interosseus muscle.

Conclusions: The prevalence of MGA in the studied sample of the Egyptian population is 20%. It is important for Hand, Orthopaedic and Neurosurgeons to be aware of this anatomic variation in order to explain paradoxical motor and sensory loss in patients.

Background: Although it is well known that rapid atrial activation causes electrical remodeling, processes of electrical remodeling at different atrial sites are still unclear. In present study, atrial electrophysiologic parameters were monitored at several atrial sites during rapid atrial stimulation for 2weeks to clarify heterogeneity of process of atrial electrical remodeling.

Methods: RAA or LAA was paced with 400bpm for 2weeks. At 4atrial sites of RAA, Bachmann's bundle (BB), IVC and LAA, AERP, AERP dispersion(AERPd) and inducibility of atrial fibrillation were evaluated at several points in pacing and recovery phase.

Results: AERP shortening (Δ AERP)was heterogeneous in 4atrial sites in process of atrial electrical remodeling. In RAA stimulation group, Δ AERP was larger in RAA and LA sites than other sites. In contrast, LAA stimulation group showed larger Δ AERP at BB site than others. Maximal AERPd was larger in LAA than RAA stimulation group. AF inducibility was highest at LA site in both groups, but inducibility was higher in LAA than RAA stimulation group.

Conclusions: In this model, process of the atrial electrical remodeling was heterogeneous in different parts of atria. Δ AERP was largest at LA site regardless of rapid pacing site, but AERPd was larger and AF inducibility was higher in LAA stimulation group than RAA stimulation group. LA seemed to play an important role in causing AF in canine rapid stimulation model of atrial electrical remodeling.