Electrophysiological Mechanisms Research Articles

Diabetes-induced electrophysiological alterations on neurosomes in ganglia of peripheral nervous system.

Diabetes mellitus (DM) leads to medical complications, the epidemiologically most important of which is diabetic peripheral neuropathy (DPN). Electrophysiology is a major component of neural functioning and several studies have been undertaken to elucidate the neural electrophysiological alterations caused by DM and their mechanisms of action. Due to the importance of electrophysiology for neuronal function, the review of the studies dealing predominantly with electrophysiological parameters and mechanisms in the neuronalsomata of peripheral neural ganglia of diabetic animals during the last 45 years is here undertaken. These studies, using predominantly techniques of electrophysiology, most frequently patch clamp for voltage clamp studies of transmembrane currents through ionic channels, have investigated the experimental DPN. They also have demonstrated that various cellular and molecular mechanisms of action of diabetic physiopathology at the level of biophysical electrical parameters are affected in DPN. Thus, they have demonstrated that several passive and active transmembrane voltage parameters, related to neuronal excitability and neuronal functions, are altered in diabetes. The majority of the studies agreed that DM produces depolarization of the resting membrane potential; alters excitability, increasing and decreasing it in dorsal root ganglia (DRG) and in nodose ganglion, respectively. They have tried to relate these changes to sensorial alterations of DPN. Concerning ionic currents, predominantly studied in DRG, the most frequent finding was increases in Na+, Ca2+, and TRPV1 cation current, and decreases in K+ current. This review concluded that additional studies are needed before an understanding of the hierarchized, time-dependent, and integrated picture of the contribution of neural electrophysiological alterations to the DPN could be reached. DM-induced electrophysiological neuronal alterations that so far have been demonstrated, most of them likely important, are either consistent with the DPN symptomatology or suggest important directions for improvement of the elucidation of DPN physiopathology, which the continuation seems to us very relevant.

Cerebral venous congestion alters brain metabolite profiles, impairing cognitive function

Vascular cognitive impairment (VCI) represents the second most common cause of dementia after Alzheimer's disease, and pathological changes in cerebral vascular structure and function are pivotal causes of VCI. Cognitive impairment caused by arterial ischemia has been extensively studied the whole time; the influence of cerebral venous congestion on cognitive impairment draws doctors’ attention in recent clinical practice, but the underlying neuropathophysiological alterations are not completely understood. This study elucidated the specific pathogenetic role of cerebral venous congestion in cognitive-behavioral deterioration and possible electrophysiological mechanisms. Using cerebral venous congestion rat models, we found these rats exhibited decreased long-term potentiation (LTP) in the hippocampal dentate gyrus and impaired spatial learning and memory. Based on untargeted metabolomics, N-acetyl-L-cysteine (NAC) deficiency was detected in cerebral venous congestion rats; supplementation with NAC appeared to ameliorate synaptic deficits, rescue impaired LTP, and mitigate cognitive impairment. In a cohort of cerebral venous congestion patients, NAC levels were decreased; NAC concentration was negatively correlated with subjective cognitive decline (SCD) score but positively correlated with mini-mental state examination (MMSE) score. These findings provide a new perspective on cognitive impairment and support further exploration of NAC as a therapeutic target for the prevention and treatment of VCI.

Decoding of the neural representation of the visual RGB color model.

RGB color is a basic visual feature. Here we use machine learning and visual evoked potential (VEP) of electroencephalogram (EEG) data to investigate the decoding features of the time courses and space location that extract it, and whether they depend on a common brain cortex channel. We show that RGB color information can be decoded from EEG data and, with the task-irrelevant paradigm, features can be decoded across fast changes in VEP stimuli. These results are consistent with the theory of both event-related potential (ERP) and P300 mechanisms. The latency on time course is shorter and more temporally precise for RGB color stimuli than P300, a result that does not depend on a task-relevant paradigm, suggesting that RGB color is an updating signal that separates visual events. Meanwhile, distribution features are evident for the brain cortex of EEG signal, providing a space correlate of RGB color in classification accuracy and channel location. Finally, space decoding of RGB color depends on the channel classification accuracy and location obtained through training and testing EEG data. The result is consistent with channel power value distribution discharged by both VEP and electrophysiological stimuli mechanisms.

PO-02-212 TWISTED FIBROTICALLY-INSULATED MYOBUNDLES CREATE THE COMMON TRACK AND PIVOTING POINTS FOR REENTRANT DRIVERS MAINTAINING PERSISTENT AF IN-VIVO

Localized reentrant drivers have been suggested to maintain persistent atrial fibrillation (perAF). However, their existence, electrophysiological mechanisms, and structural substrates in-vivo are controversial. Define AF driving mechanism in-vivo and ex-vivo in a perAF canine model. A clinically relevant canine model (n=5) of self-sustained (4 months) perAF was developed to study AF maintaining mechanisms both in-vivo and ex-vivo by integrated 3D imaging, including high-resolution near-infrared optical mapping (NIOM, 0.3-0.5mm resolution), contrast-enhanced magnetic resonance imaging (CE-MRI, 0.15mm resolution). Transmural fibrosis was validated with histology. CE-MRI was used to quantitatively analyze 3D atrial structure, including transmural fiber orientation and fibrosis content in the sub-epi, intramural, and sub-endocardial layers. In all canine models (n=5), sequential in-vivo to ex-vivo sub-surface NIOM and 3D CE-MRI revealed that the self-sustained perAF was primarily maintained by localized reentrant drivers with temporal stability 53±17% (n=10), which recurrent on the same arrhythmogenic hubs. The 3D structure of the arrhythmogenic driver hubs includes a common intramural reentry track and multiple return paths formed by fibrotically-insulated bundles. The in-vivo spatio-temporal activation patterns of reentrant drivers were preserved ex-vivo (Figure A), including driver AFCL (91±7 ms vs 96±12 ms, p>0.05) and temporal driver stability (51±8% vs 52±6%, n=4, p>0.05). Targeted ablation of the driver reentrant tracks terminated or converted AF to slower tachycardia. Quantitative CE-MRI analysis of 3D myofiber orientations revealed that the transmural fiber twist along the common reentry tracks and pivoting points is greater than in non-driver regions (Figure B-C). The driver reentrant tracks had increased interstitial fibrotic strands and significantly higher intramural fibrosis than the neighboring non-driver regions (Figure D-E). Our results provide in-vivo proof-of-concept that spatially stable reentrant drivers are a mechanism of perAF maintenance. Intramural fibrotic strands and fibrotically-insulated myobundles in regions with the highest transmural myofiber twist which may form the common tracks and pivoting points for return paths of the spatially-stable reentrant AF driver.

PO-04-043 ALTERNATING PR AND RP INTERVALS PRIOR TO COMPLETE AV BLOCK: THE CHICKEN OR THE EGG?

The incidence of permanent pacemaker implantation for high-degree AV block after transcatheter aortic valve replacement (TAVR) is approximately 6%, because of mechanical damage to the conduction system. We report a novel ECG marker, i.e. inverse decremental conduction (IDC), that heralds paroxysmal AV block. Case report and exploration of the electrophysiological mechanism. N/A A 73-year-old male with severe symptomatic aortic stenosis underwent TAVR with a balloon-expandable valve. On day 1 post-TAVR, his 12-lead ECG revealed sinus rhythm with a normal PR interval and unchanged RBBB with a left anterior fascicular block (LAFB). The patient was discharged with mobile cardiac outpatient telemetry. Although the patient was asymptomatic, he was asked to come to the emergency department (ED) after his monitor detected a 3.5-second pause during sleep. Shortly after a 12-lead ECG was obtained in the ED, he experienced two sudden cardiac arrests due to complete AV block and asystole requiring CPR and transcutaneous pacing. He underwent emergent implantation of a dual-chamber pacemaker. His ECG in the ED reveals alternating PR intervals (Figure). The first impression of the alternating PR intervals is a dual AV nodal physiology with a 2:1 block in the fast pathway, a relatively benign ECG sign. However, paroxysmal AV block and recent history of TAVR suggested a His-Purkinje injury with block at the subnodal level. More specifically, TAVR-related IDC in the left posterior fascicle (LPF) underlies alternating PR intervals in the setting of RBBB and LAFB. In other words, the PR length is proportional to the preceding RP length, i.e. a longer RP leads to a longer subsequent PR and vice versa due to IDC in LPF. The injured His-Purkinje fibers may lose their all-or-none conduction property and display IDC post-TAVR. This manifests as LBBB with a duration proportional to the preceding RP or RR interval or as prolongation of the PR interval with lengthening of the preceding RP interval in presence of RBBB. IDC in the His-Purkinje may be masked by decremental conduction in the AV node and is often under-recognized. Once the PR interval prolongs with lengthening of the preceding RP interval post-TAVR, unrelated to vagal stimulation, insertion of a temporary or permanent pacemaker is urgently indicated. Alternating PR intervals can be a benign finding, but in this case were linked with paroxysmal AV block secondary to IDC, with resultant cardiac arrest post-TAVR.

Eltoprazine modulated gamma oscillations on ameliorating L-dopa-induced dyskinesia in rats.

Parkinson's disease (PD) is a pervasive neurodegenerative disease, and levodopa (L-dopa) is its preferred treatment. The pathophysiological mechanism of levodopa-induced dyskinesia (LID), the most common complication of long-term L-dopa administration, remains obscure. Accumulated evidence suggests that the dopaminergic as well as non-dopaminergic systems contribute to LID development. As a 5-hydroxytryptamine 1A/1B receptor agonist, eltoprazine ameliorates dyskinesia, although little is known about its electrophysiological mechanism. The aim of this study was to investigate the cumulative effects of chronic L-dopa administration and the potential mechanism of eltoprazine's amelioration of dyskinesia at the electrophysiological level in rats. Neural electrophysiological analysis techniques were conducted on the acquired local field potential (LFP) data from primary motor cortex (M1) and dorsolateral striatum (DLS) during different pathological states to obtain the information of power spectrum density, theta-gamma phase-amplitude coupling (PAC), and functional connectivity. Behavior tests and AIMs scoring were performed to verify PD model establishment and evaluate LID severity. We detected exaggerated gamma activities in the dyskinetic state, with different features and impacts in distinct regions. Gamma oscillations in M1 were narrowband manner, whereas that in DLS had a broadband appearance. Striatal exaggerated theta-gamma PAC in the LID state contributed to broadband gamma oscillation, and aperiodic-corrected cortical beta power correlated robustly with aperiodic-corrected gamma power in M1. M1-DLS coherence and phase-locking values (PLVs) in the gamma band were enhanced following L-dopa administration. Eltoprazine intervention reduced gamma oscillations, theta-gamma PAC in the DLS, and coherence and PLVs in the gamma band to alleviate dyskinesia. Excessive cortical gamma oscillation is a compelling clinical indicator of dyskinesia. The detection of enhanced PAC and functional connectivity of gamma-band oscillation can be used to guide and optimize deep brain stimulation parameters. Eltoprazine has potential clinical application for dyskinesia.

Arginine vasopressin effects on membrane potentials of preoptic area temperature-sensitive and -insensitive neurons in rat hypothalamic tissue slices

Arginine vasopressin (AVP) plays a hypothermic regulatory role in thermoregulation and is an important endogenous mediator in this mechanism. In the preoptic area (POA), AVP increases the spontaneous firing and thermosensitivity of warm-sensitive neurons and decreases those of cold-sensitive and temperature-insensitive neurons. Because POA neurons play a crucial role in precise thermoregulatory responses, these findings indicate that there is an association between the hypothermia and changes in the firing activity of AVP-induced POA neurons. However, the electrophysiological mechanisms by which AVP controls this firing activity remain unclear. Therefore, in the present study, using in vitro hypothalamic brain slices and whole-cell recordings, we elucidated the membrane potential responses of temperature-sensitive and –insensitive POA neurons to identify the applications of AVP or V1a vasopressin receptor antagonists. By monitoring changes in the resting potential and membrane potential thermosensitivity of the neurons before and during experimental perfusion, we observed that AVP increased the changes in the resting potential of 50% of temperature-insensitive neurons but reduced them in others. These changes are because AVP enhances the membrane potential thermosensitivity of nearly 50% of the temperature-insensitive neurons. On the other hand, AVP changes both the resting potential and membrane potential thermosensitivity of temperature-sensitive neurons, with no differences between the warm- and cold-sensitive neurons. Before and during AVP or V1a vasopressin receptor antagonist perfusion, no correlation was observed between changes in the thermosensitivity and membrane potential of all neurons. Furthermore, no correlation was observed between the thermosensitivity and membrane potential thermosensitivity of the neurons during experimental perfusion. In the present study, we found that AVP induction did not result in any changes in resting potential, which is unique to temperature-sensitive neurons. The study results suggest that AVP-induced changes in the firing activity and firing rate thermosensitivity of POA neurons are not controlled by resting potentials.

Transcatheter ablation in patients with Brugada syndrome.

Since the first description of Brugada syndrome (BrS), several studies were carried out aimed at diagnosis, arrhythmic risk stratification, and available strategies for sudden death prevention. In high-risk patients, the use of an implantable cardiac defibrillator was an evident option since the first description of the syndrome. Nevertheless, this strategy, while proven, as expected, to be effective in sudden death prevention, does not prevent arrhythmias and may not be an adequate or accepted solution for all patients. The need of a non-pharmacological therapy as a potential solution based on the electrophysiological mechanisms underlying the syndrome, led to search for substrate as target for catheter ablation. Advances in the tools, technology, and technical approach enabled to launch studies aimed at mapping the epicardium of patients with BrS in order to identify and ablate the substrate. As described in previous work and in our experience, an anatomically identifiable electrical substrate, which correspond to the typical ECG, is the ablation target. Complete substrate is better identified in a larger area with sodium-channel-blockers. Ablation of all abnormal electrical potentials is able to normalize the ECG and prevent arrhythmias induction. Encouraging preliminary data, if confirmed by longer follow-up and by multicentre randomized study, could change the whole therapeutic management in BrS patients.

Myocardial infarction-related ventricular arrhythmias

Ventricular arrhythmias are among the most serious complications of myocardial infarction that defi ne not only increased morbidity and mortality, but also signifi cantly impaired quality of life. The pathogenesis of ventricular arrhythmias that arise during and after myocardial infarction is a combination of various triggering and modulating factors. We present a summary of the main structural and functional changes that occur with myocardial ischemia and create substrate for ventricular arrhythmias. The electrophysiological mechanisms underlying infarction-related ventricular arrhythmias are reviewed, as well as the most common pharmacological and non-pharmacological treatment’s strategies.

42. Atrial Fibrillation and Hypertension in Prolanis Community in Bandung City: A Quantitative-Descriptive Study

Background: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia which often is asymptomatic and undiagnosed. One of the risk factors for atrial fibrillation include high blood pressure. Hypertension itself, based on International Society of Hypertension 2020 is defined when systolic blood pressure $140mmHg and/or diastolic blood pressure $90mmHg. In Indonesia, we have PROLANIS (Program Pengelolaan Penyakit Kronis), a program which is held by Ministry of Health in Indonesia to manage chronic disease such as hypertension. Objective: This descriptive study is aimed to identify the prevalence of atrial fibrillation in hypertensive patient among PROLANIS community in Bandung City. Method: We performed prospective screening using a six-leads FDA approved ECG mobile in twenty-one primary care among PROLANIS community during March-October 2022. Result: We collected 692 data from PROLANIS community in twenty-one primary care in Bandung City. AF in normotensive patient was 2.7% (n = 10), AF in stage 1 hypertension was 4.37% (n = 10) and AF in stage 2 hypertension was 4.5% (n = 4). Conclusion: Hypertension and AF often coexist. Patient with hypertension have 1.7-fold higher risk of developing AF than normotensive individual. Hypertension may induce early and progressive changes in left atrium anatomy and function, which may promote AF through a variety of electrophysiological mechanism. We found studies which conducted by the same method (using mobile electrocardiogram), AF was found 8.1% in hypertensive patient. The diagnosis of atrial fibrillation from the tools warrants further cardiological evaluation but it could be helpful in patients at cardiovascular risk for better prevention.

Median Nerve Stimulation for Treatment of Tics: Randomized, Controlled, Crossover Trial.

A prior study showed that rhythmic, but not arrhythmic, 12 Hz stimulation of the median nerve (MNS) entrained the sensorimotor cortex EEG signal and found that 10 Hz MNS improved tics in Tourette syndrome (TS). However, no control condition was tested, and stimulation blocks lasted only 1 min. We set out to replicate the TS results and to test whether tic improvement occurs by the proposed cortical entrainment mechanism. Preregistration was completed at ClinicalTrials.gov, under number NCT04731714. Thirty-two people with TS, age 15-64, completed two study visits with repeated MNS on and off blocks in random order, one visit for rhythmic and one for arrhythmic MNS. Subjects and staff were blind to order; a video rater was additionally blind to stimulation and to the order of visits and blocks. Rhythmic MNS at 10 Hz improved tics. Both rhythmic and arrhythmic 12 Hz MNS improved tic frequency, intensity, and urges, but the two treatments did not differ significantly. Participant masking was effective, and there was no carryover effect. Several participants described a dramatic benefit. Discomfort was minimal. There was no evidence that the MNS benefit persisted after stimulation ended. These results replicate the tic benefit from MNS but show that the EEG entrainment hypothesis cannot explain that benefit. Another electrophysiological mechanism may explain the benefit; alternatively, these data do not exclude a placebo effect.

Effectiveness and electrophysiological mechanisms of focal vibration on upper limb motor dysfunction in patients with subacute stroke: A randomized controlled trial

Upper limb motor dysfunction is a common complication after stroke, which has a negative impact on the daily life of the patients. Focal vibration (FV) has been used to improve upper limb motor function in acute and chronic stroke patients, but its application in subacute stroke patients has not been extensively explored. Therefore, the purpose of this study was to explore the therapeutic effect of FV on upper limb motor function in subacute stroke patients and its underlying electrophysiological mechanism. Twenty-nine patients were enrolled and randomized into two groups: a control group and a vibration group. The control group were treated with conventional therapy including passive and active physical activity training, standing and sitting balance exercises, muscle strength training, hand extension and grasping exercises. The vibration group were given conventional rehabilitation and vibration therapy. A deep muscle stimulator (DMS) with a frequency of 60 Hz and an amplitude of 6 mm was used to provide vibration stimulation, which was sequentially applied along the biceps muscle to the flexor radialis of the affected limb for 10 min, once a day, and 6 times a week. Both groups received treatments for 4 consecutive weeks. In the vibration group, the motor evoked potential (MEP) latency and the somatosensory evoked potential (SEP) latency were significantly shortened (P < 0.05) immediately and 30 min after vibration; the SEP amplitude and MEP amplitude were significantly increased (P < 0.05) immediately and 30 min after vibration. The MEP latency (P = 0.001) and SEP N20 latency (P = 0.001) were shortened, and the MEP amplitude (P = 0.011) and SEP N20 amplitude (P = 0.017) were significantly increased after 4 weeks in the vibration group. After 4 consecutive weeks, the vibration group showed significant improvements in Modified Ashworth Scale (MAS) (P = 0.037), Brunnstrom stage for upper extremity (BS-UE) (P = 0.020), Fugl-Meyer assessment for upper extremity (FMA-UE) (P = 0.029), Modified Barthel Index (MBI) (P = 0.024), and SEP N20 (P = 0.046) compared to the control group. The Brunnstrom stage for hand (BS-H) (P = 0.451) did not show significant differences between the two groups. This study showed that FV was effective in improving upper limb motor function in subacute stroke patients. The underlying mechanism of FV may be that it enhances the efficacy of sensory pathways and induces plastic changes in the sensorimotor cortex.

The effect of trait anxiety on the time course of self-relevant processing: Evidence from the perceptual matching task

Studies have widely reported that trait anxiety is associated with a range of cognitive biases toward external negative emotional stimuli. However, few studies have examined whether trait anxiety modulates intrinsic self-relevant processing. This study investigated the electrophysiological mechanism underlying trait anxiety’s modulating effect on self-relevant processing. Event-related potentials (ERPs) were recorded while participants performed a perceptual matching task that assigned an arbitrary geometric shape to an association with a “self” or “non-self” label. Results showed larger N1 amplitudes under self-association than under friend-association conditions, and smaller P2 amplitudes for self- than for stranger-association conditions in individuals with high trait anxiety. However, these self-biases in the N1 and P2 stages were not observed in those with low trait anxiety until the later N2 stage, in which the self-association condition provoked smaller N2 amplitudes than the stranger-association condition. In addition, both high and low trait anxiety individuals showed larger P3 amplitudes for the self-association condition than for the friend- and stranger-association conditions. These findings suggest that, although both high and low trait anxiety individuals showed self-bias, high trait anxiety individuals distinguished between self-relevant and non-self-relevant stimuli at an earlier stage, which may reflect hypervigilance to self-relevant stimuli.

Epicardial Dispersion of Repolarization Promotes the Onset of Reentry in Brugada Syndrome: A Numerical Simulation Study

The Brugada syndrome (BrS) is a cardiac arrhythmic disorder responsible for sudden cardiac death associated with the onset of ventricular arrhythmias, such as reentrant ventricular tachycardia and fibrillation. The mechanisms which lead to the onset of such electrical disorders in patients affected by BrS are not completely understood, yet. The aim of the present study is to investigate by means of numerical simulations the electrophysiological mechanisms at the basis of the morphology of electrocardiogram (ECG) and the onset of reentry associated with BrS. To this end, we consider the Bidomain equations coupled with the ten Tusscher–Panfilov membrane model, on an idealized wedge of human right ventricular tissue. The results have shown that: (1) epicardial dispersion of repolarization, generated by the coexistence of regions of early and late repolarization, due to different modulation of the I_mathrm{{CaL}} current, produces ECG waveforms exhibiting qualitatively the typical BrS morphology, characterized by ST elevation and partially negative T-waves; (2) epicardial dispersion of repolarization promotes the onset of reentry during the implementation of the programmed stimulation protocol, because of the conduction block occurring when a premature beat reaches the border of late repolarizing regions; and (3) the modulation of the I_mathrm{{to}} current affects the duration of reentry, which becomes sustained with a remarkable increase of I_mathrm{{to}} in the subepicardial layers.

Brugada Syndrome: From Molecular Mechanisms and Genetics to Risk Stratification

Brugada syndrome (BrS) is a rare hereditary arrhythmia disorder, with a distinctive ECG pattern, correlated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD) in young adults. BrS is a complex entity in terms of mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The main electrophysiological mechanism of BrS requires further research, with prevailing theories centered on aberrant repolarization, depolarization, and current-load match. Computational modelling, pre-clinical, and clinical research show that BrS molecular anomalies result in excitation wavelength (k) modifications, which eventually increase the risk of arrhythmia. Although a mutation in the SCN5A (Sodium Voltage-Gated Channel Alpha Subunit 5) gene was first reported almost two decades ago, BrS is still currently regarded as a Mendelian condition inherited in an autosomal dominant manner with incomplete penetrance, despite the recent developments in the field of genetics and the latest hypothesis of additional inheritance pathways proposing a more complex mode of inheritance. In spite of the extensive use of the next-generation sequencing (NGS) technique with high coverage, genetics remains unexplained in a number of clinically confirmed cases. Except for the SCN5A which encodes the cardiac sodium channel NaV1.5, susceptibility genes remain mostly unidentified. The predominance of cardiac transcription factor loci suggests that transcriptional regulation is essential to the Brugada syndrome's pathogenesis. It appears that BrS is a multifactorial disease, which is influenced by several loci, each of which is affected by the environment. The primary challenge in individuals with a BrS type 1 ECG is to identify those who are at risk for sudden death, researchers propose the use of a multiparametric clinical and instrumental strategy for risk stratification. The aim of this review is to summarize the latest findings addressing the genetic architecture of BrS and to provide novel perspectives into its molecular underpinnings and novel models of risk stratification.

Temporal and Spatial Changes of Proarrhythmic Substrate in Premature Ventricular Contraction–Induced Cardiomyopathy

BackgroundThe changes in proarrhythmic substrates and malignant ventricular arrhythmia mechanisms caused by premature ventricular contraction–induced cardiomyopathy (PVCCM) remain unclear. ObjectivesThe goal of this study was to establish the electrophysiological mechanism of how high-load PVC causes malignant arrhythmia. MethodsThirteen swine were exposed to 50% paced PVC from the right ventricular apex for 12 weeks (PVCCM, n = 6) and no pacing for 12 weeks (control, n = 7). Cardiac function was quantified biweekly with echocardiography. Computed tomography scans and electrophysiological examinations were performed monthly to dynamically evaluate the changes in the cardiac structure and the arrhythmogenic substrate. ResultsThe decreases in the cardiac function and ventricular enlargement in the PVCCM group were significant after 12 weeks of PVC stimulation compared with the control group (P < 0.001). Electrophysiological examination found that the ventricular effective refractory period dispersion (0.071 ± 0.008), area of the low-voltage zone (9.41 ± 1.55 cm2), and malignant ventricular arrhythmia inducibility (33.3%) of the PVCCM group increased significantly at week 8 after pacing (P < 0.001 vs the control group); these changes slowed down after 8 weeks. Moreover, the distribution of the low-voltage zone presented obvious spatial heterogeneity, especially in the anterior wall of the right ventricle, accompanied by delayed activation in the sinus rhythm (67 ± 13 milliseconds). Consistently, the proportion of ventricular fibrosis– and expression-related proteins were significantly increased in the PVCCM group (P < 0.001), especially in the right ventricle. Moreover, proteomic analysis confirmed the spatial profile of these fibrotic changes in the PVCCM group. ConclusionsHigh-burden PVC can cause significant temporal and spatial heterogeneity changes in proarrhythmic substrates, which are potentially related to the upregulation of calcium signaling caused by asynchronous activation.

Neural evidence for functional roles of tactile and visual feedback in the application of myoelectric prosthesis

Objective. The primary purpose of this study was to investigate the electrophysiological mechanism underlying different modalities of sensory feedback and multi-sensory integration in typical prosthesis control tasks. Approach. We recruited 15 subjects and developed a closed-loop setup for three prosthesis control tasks which covered typical activities in the practical prosthesis application, i.e. prosthesis finger position control (PFPC), equivalent grasping force control (GFC) and box and block control (BABC). All the three tasks were conducted under tactile feedback (TF), visual feedback (VF) and tactile-visual feedback (TVF), respectively, with a simultaneous electroencephalography (EEG) recording to assess the electroencephalogram (EEG) response underlying different types of feedback. Behavioral and psychophysical assessments were also administered in each feedback condition. Results. EEG results showed that VF played a predominant role in GFC and BABC tasks. It was reflected by a significantly lower somatosensory alpha event-related desynchronization (ERD) in TVF than in TF and no significant difference in visual alpha ERD between TVF and VF. In PFPC task, there was no significant difference in somatosensory alpha ERD between TF and TVF, while a significantly lower visual alpha ERD was found in TVF than in VF, indicating that TF was essential in situations related to proprioceptive position perception. Tactile-visual integration was found when TF and VF were congruently implemented, showing an obvious activation over the premotor cortex in the three tasks. Behavioral and psychophysical results were consistent with EEG evaluations. Significance. Our findings could provide neural evidence for multi-sensory integration and functional roles of tactile and VF in a practical setting of prosthesis control, shedding a multi-dimensional insight into the functional mechanisms of sensory feedback.

Right atrial tachycardia after atrial fibrillation ablation: prevalence, clinical characteristics, electrophysiological mechanisms, and long-term outcomes.

This study aims to evaluate the prevalence, clinical characteristics, electrophysiological mechanisms, and long-term outcomes of right atrial tachycardia (AT) in patients who underwent ablation for atrial fibrillation (AF). From March 2010 to December 2020, 220 consecutive patients undergoing index AF ablation were referred for post-ablation AT recurrence. Thirty-five patients (35/220, 15.9%) with right AT recurrence (25 men; mean age 59.3 ± 10.2years) were enrolled. These patients were divided into groups with right ATs exclusively (group 1) and right combined with left ATs (group 2). Fifty-three ATs were mapped in all patients, with thirty-nine ATs originating from the right atrium. The detailed distribution of all right ATs was 22 in the cavo-tricuspid isthmus (CTI), 6 in the ostium of superior vein cava (SVC), 4 in the right free wall, 4 in the right anterior atrial septum, 2 in coronary sinus ostium, and 1 in crista terminalis. Group 2 had a significantly higher incidence of typical atrial flutter (AFL) than group 1 (11/12, 90.9% vs. 12/24, 50.0%, P = 0.03). During the mean follow-up of 43.6 ± 25.2months after the index AT ablation, the recurrence rate of AT/AF was 22.9% (8/35), and it was lower in group 1 than in group 2 (8.3% vs. 54.5%, P = 0.01). Right AT is relatively less common post-AF ablation. The CTI-dependent AFL and the ostium of SVC-derived focal AT constituted the major components of right ATs, suggesting the importance of ablation- and anatomy-related arrhythmogenic effects in the right atrium.

Mechanisms of late arrhythmia recurrence after initially successful pulmonary vein isolation in patients with atrial fibrillation.

Catheter ablation is an effective treatment for atrial fibrillation (AF,) but arrhythmia recurrence occurs in a relevant number of patients. Mechanisms of late occurring arrhythmias after ablation procedures are not fully understood. We analyzed electrophysiological mechanisms of early and late arrhythmia recurrences in patients who underwent radiofrequency-based catheter ablation of AF. Consecutive patients who underwent repeat ablation procedures after initial pulmonary vein isolation (PVI) for symptomatic arrhythmia recurrence were analyzed. A total of 110 consecutive patients who underwent catheter ablation for paroxysmal (79%) or persistent AF (21%) were included. Forty-seven patients suffered from early arrhythmia recurrence (group #1: 3-24 months), 29 patients from mid-term arrhythmia recurrences (group #2: 2-5 years), and 34 patients from late arrhythmia recurrences (group #3:>5 years). Electrical PV reconnection was found in 98% in group #1, 72% in group #2 and 56% in group #3 (p<.001). Mode of arrhythmia recurrence was organized tachycardia in 25%, 28%, and 65% of patients in groups #1, #2, and #3 (p=.001), respectively. Patients with late arrhythmia recurrence had more pronounced left atrial low voltage as compared to patients with early arrhythmia recurrence based on two published scoring system. Electrical PV reconnection was found in the majority of patients with early AF recurrence after PVI. In patients with late arrhythmia recurrences this mechanism may play an inferior role, with many patients presenting without PV reconnection, but with LA structural alterations. Thus, early and late occurring arrhythmia recurrence after catheter ablation may be the same symptom of different diseases.

Orexin-A aggravates cognitive deficits in 3xTg-AD mice by exacerbating synaptic plasticity impairment and affecting amyloid β metabolism

Dementia is the main clinical feature of Alzheimer's disease (AD). Orexin has recently been linked to AD pathogenesis, and exogenous orexin-A (OXA) aggravates spatial memory impairment in APP/PS1 mice. However, the effects of OXA on other types of cognitive deficits, especially in 3xTg-AD mice exhibiting both plaque and tangle pathologies, have not been reported. Furthermore, the potential electrophysiological mechanism by which OXA affects cognitive deficits and the molecular mechanism by which OXA increases amyloid β (Aβ) levels are unknown. In the present study, the effects of OXA on cognitive functions, synaptic plasticity, Aβ levels, tau hyperphosphorylation, BACE1 and NEP expression, and circadian locomotor rhythm were evaluated. The results showed that OXA aggravated memory impairments and circadian rhythm disturbance, exacerbated hippocampal LTP depression, and increased Aβ and tau pathologies in 3xTg-AD mice by affecting BACE1 and NEP expression. These results indicated that OXA aggravates cognitive deficits and hippocampal synaptic plasticity impairment in 3xTg-AD mice by increasing Aβ production and decreasing Aβ clearance through disruption of the circadian rhythm and sleep-wake cycle.