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Objective: The primary goal was to determine the performance of the cross‐section area swelling rate (CSASR) for diagnostic and therapeutic purposes based on the reference standard of electrodiagnosis examination (EDX) in this diagnostic test study. Methods: First, patients with symptoms like unilateral carpal tunnel syndrome (CTS), cubital tunnel syndrome (CuTS), and radial nerve compression (RNC) underwent EDX and ultrasound examination. Second, patients with positive ultrasound were calculated for the CSASR of diseased nerve. Based on previously established CSASR criteria, each patient was categorized as having or not having peripheral nerve entrapment, and for those meeting diagnostic criteria, non‐surgical or surgical treatment was recommended. Then, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy rate (ACC) of ultrasound diagnosis and therapeutic decision‐making were calculated based on the reference standard of EDX that had been historically used in the practice. Results: The total sensitivity, specificity, PPV, NPV, and ACC of ultrasound diagnosis are respectively 93.4, 85.2, 94.7, 82.1, and 91.3%. Which of therapeutic decision‐making by ultrasound are, respectively, 83.3, 52.2, 78.4, 60.0, and 73.2%. Conclusion: The sensitivity and Youden's index of CSASR diagnostic threshold for CuTS is higher than other ultrasound methods. The CSASR diagnostic threshold for CuTS has a potential diagnostic role, but the current date is still not enough to support the potential diagnostic role for CTS or RNS. There is insufficient evidence to suggest that CSASR for CuTS can be used in isolation for diagnosis. Additional research is needed to confirm the diagnostic role of CSASR. The current results suggest that this ultrasound examination method is not suitable for therapeutic decision‐making. [ABSTRACT FROM AUTHOR]

Objective To summarize the electrophysiological and muscle pathological characteristics of Lambert - Eaton myasthenic syndrome (LEMS). Methods and Results Twelve LEMS patients referred to China - Japan Friendship Hospital between January 2010 and December 2021 were included. Clinically, they all showed proximal muscle weakness and reduced or disappeared tendon reflexes. Electrophysiologically, all 12 patients showed decreased compound muscle action potential (CMAP) amplitudes, normal distal motor latency (DML), and normal motor and sensory conduction velocities. Ten patients underwent repetitive nerve stimulation (RNS) test: all had amplitude increments of more than 100% at high - frequency RNS, and 8 had amplitude decrements of more than 15% at low - frequency RNS. Three patients completed the post-exercise facilitation (PEF) test: the ulnar nerve CMAP amplitude reached a peak immediately after maximum voluntary contraction of the abductor digiti minimi for 5-10 s and then gradually decreased to near baseline level after contraction for 60 s; the ulnar nerve CMAP amplitude reached a peak immediately after maximum voluntary contraction for 10 s, and then rapidly decreased to near baseline level after 15 s. On needle EMG, 8 patients showed normal motor unit action potential (MUAP), 3 showed short - duration MUAP mimicking myopathy, and one showed long - duration MUAP mimicking neuropathy. Two patients with normal MUAP underwent biceps biopsy, which showed selective type - fiber atrophy. Conclusions Electrophysiologically, CMAP amplitudes of LEMS patients are usually diffusely low or borderline. LEMS patients have amplitude increments of more than 100% at high-frequency RNS, and some have amplitude decrements of more than 15% at low-frequency RNS. PEF Needle EMG is usually normal, but some show myogenic lesions, and some show neurogenic lesions. Muscle biopsy shows selective type - fiber atrophy. Needle EMG myogenic lesion may not be associated with pathologically selective type - fiber atrophy. [ABSTRACT FROM AUTHOR]

Background: Deltoid muscle detachment and atrophy have been reported to occur after shoulder surgery. Purpose: To investigate the 2-year changes in deltoid muscle structure and function after arthroscopic rotator cuff repair (ARCR) using magnetic resonance imaging (MRI) and electrophysical examination. Study Design: Case series; Level of evidence, 4. Methods: A total of 72 patients (72 shoulders) who underwent ARCR between 2015 and 2020 were enrolled. Whole deltoid muscle volume and regional (anterior, lateral, and posterior) muscle thicknesses were determined on T2-weighted MRI scans of both shoulders taken preoperatively and at 1, 3, 6, 12, and 24 months postoperatively, and their correlations with compound muscle action potentials (CMAPs), shoulder abduction muscle strength, and Constant scores were investigated. Comparison between groups was performed using paired or Student t tests, and the relationship between deltoid muscle volume and various factors was determined using Pearson correlation analysis. Results: The volume of the deltoid muscle on the affected side decreased from 44,369 ± 12,371 mm3 preoperatively to 38,139 ± 10,615 mm3 at 1 month postoperatively (P <.05), representing a 14% decrease. The deltoid muscle volume of the contralateral side also significantly decreased during the same time frame, from 43,278 ± 12,248 to 40,273 ± 11,464 mm3 (P <.05), representing a 7% decrease at 1 month postoperatively. Subsequently, the deltoid muscle volume on both sides recovered to preoperative levels at 12 months and was maintained at 24 months. Only the thickness of the anterior part of the deltoid was markedly decreased, from 13.9 ± 3.7 mm preoperatively to 12.0 ± 3.2 mm at 1 month postoperatively (P <.05), representing a 14% reduction. The CMAP amplitude showed a significant decrease at 1 month postoperatively; however, no significant difference was observed after 12 months when compared with the preoperative values or the values on the contralateral side. Positive correlations were found between deltoid muscle volume and CMAP amplitude at 24 months as well as between deltoid muscle volume and shoulder abduction muscle strength (R 2 = 0.698; P <.05) and Constant score (R 2 = 0.133; P <.05). Conclusion: Our study demonstrated that the early structural and functional decline of the deltoid muscle after ARCR was fully recovered within 1 year, confirming that this procedure does not negatively affect the deltoid muscle. [ABSTRACT FROM AUTHOR]

Background: Evoked potentials are electrical events recorded in the cerebral cortex after stimulation of a sense organ. They are non-invasive studies used to assess visual conduction pathways through optic nerves and the brain. Visual evoked potentials (VEPs) are affected by physiological factors such as age, sex, visual acuity, head circumference, and pupillary size. VEPs are used to diagnose and assess retinal pathology in ophthalmology, neurological pathology affecting the optic nerve and/or brain. Aims and Objectives: The aim of the study was to investigate gender-related alteration in parameters of VEP, to obtain relationship between head circumference with latency and amplitude values of VEP parameters. To investigate whether gender, head size, or both considered as an important factor influencing VEPs parameters. Materials and Methods: A cross-sectional study among 50 participants aged 19-29 with normal visual acuity and VEP recordings such as latencies and peak amplitude was performed using a RMS EMG EP Mark II machine. Results: The study examined the mean latencies for N75, P100, and N145 in the left and right eyes of 25 female and 25 male participants. No significant differences were found in N75, P100, and N145 latencies between genders. However, females showed slightly higher amplitude differences than males. In the right eye, females showed higher N75 latency and P100 latency, but no significant gender differences were found for P100 latency or N145 latency. The Pearson correlation coefficient showed weak correlations between head circumference and VEP parameters for females and males, while no significant correlations were observed for females. Conclusion: VEPs are sensitive tools for evaluating visual conduction pathways in eye disease patients. However, gender differences in VEP parameters were not significant in this study, and a negative correlation was found between head size and VEP amplitude. [ABSTRACT FROM AUTHOR]

Ischemic heart disease is caused by coronary artery occlusion. Despite the increasing number and success of interventions for restoring coronary artery perfusion, myocardial ischemia–reperfusion (I/R) injury remains a significant cause of morbidity and mortality worldwide. Inspired by the impact of I/R on the Cx43 trafficking to the intercalated discs (ICDs), we aim to explore the potential mechanisms underlying the downregulation of Cx43 in ICDs after myocardial I/R. Gene set enrichment analysis (GSEA), Western blotting, and immunofluorescence experiments showed that Myocardial I/R activated the P38MAPK signaling pathway and promoted microtubule depolymerization. Inhibition of P38MAPK signaling pathway activation attenuated I/R-induced microtubule depolymerization. The ability of SB203580 to recover the distribution of Cx43 and electrophysiological parameters in I/R myocardium depended on microtubule stability. Our study suggests that microtubule depolymerization caused by the activation of the P38MAPK signaling pathway is an important mechanism underlying the downregulation of Cx43 in ICDs after myocardial I/R. [ABSTRACT FROM AUTHOR]

Improving health-related quality of life (QoL) is crucial for managing Parkinson's disease. However, QoL outcomes after deep brain stimulation (DBS) of the subthalamic nucleus (STN) vary considerably. Current approaches lack integration of demographic, patient-reported, neuroimaging, and neurophysiological data to understand this variability. This study used explainable machine learning to analyze multimodal factors affecting QoL changes, measured by the Parkinson's Disease Questionnaire (PDQ-39) in 63 patients, and quantified each variable's contribution. Results showed that preoperative PDQ-39 scores and upper beta band activity (>20 Hz) in the left STN were key predictors of QoL changes. Lower initial QoL burden predicted worsening, while improvement was associated with higher beta activity. Additionally, electrode positions along the superior-inferior axis, especially relative to the z = −7 coordinate in standard space, influenced outcomes, with improved and worsened QoL above and below this marker. This study emphasizes a tailored, data-informed approach to optimize DBS treatment and improve patient QoL. [ABSTRACT FROM AUTHOR]

Background: In electrophysiological procedures, multiple punctures on the femoral vein can be necessary depending on the number of catheters required. The femoral vein is typically located indirectly by using its anatomical relationship to the artery as a reference. However, this conventional approach can lead to significant complications, including bleeding, peri-interventional transfusion, pseudoaneurysms, or arteriovenous fistulas. Despite these risks, there is limited evidence comparing the safety of ultrasound-guided venipuncture versus the conventional technique in electrophysiological procedures. Objective: This study aimed to evaluate the impact of ultrasound-guided venipuncture on vascular access complications in electrophysiological procedures and to identify associated risk factors. Methods: In this single-center trial, patients scheduled for electrophysiological procedures at Ulm University Heart Center, Germany, were enrolled between November 2021 and October 2023. Venipuncture in the groin was performed using either the conventional or an ultrasound-guided approach. The primary composite endpoint was defined as peri-interventional major vascular access complications (Bleeding Academic Research Consortium (BARC) ≥2 bleeding, pseudoaneurysms, arteriovenous fistulas, and peri-interventional transfusion) and minor complications (BARC 1). Results: A total of 1370 patients were included: 749 in the conventional group and 621 in the ultrasound group. The primary endpoint was achieved in 19.2% of the conventional group and 12.1% of the ultrasound group (p < 0.001). An increased sheath diameter and a higher number of venous accesses were identified as risk factors for the primary endpoint. Conclusions: Ultrasound guidance for venous groin puncture in electrophysiological procedures reduces access-related complications, supporting its use with careful attention to sheath size and number. [ABSTRACT FROM AUTHOR]

Background: Previous research highlighted variability in electrocardiogram (ECG) readings across patient positions, particularly in the context of COVID‐19 patients with pulmonary complications requiring prone positioning as part of the treatment. Objective: This study aimed to elucidate the effects of prone positioning on ECG parameters and explore its association with the severity of COVID‐19. Methods: A prospective cohort study involved 60 patients diagnosed with COVID‐19 and presenting pulmonary complications. ECGs were recorded in both supine and prone positions, and analyzed for various parameters including heart rate, QRS axis, and QTc interval. Clinical severity was assessed using APACHE II scores and SpO2/FiO2 ratios. Results: Prone positioning led to an increase in heart rate (mean difference: 2.100, 95% CI: 0.471–3.729, p = 0.012), with minor shifts in the QRS axis. Heart rate and QRS axis demonstrated strong positive correlations between positions, with Pearson's correlation coefficients of 0.927 and 0.894, respectively. The study also found a significant association between prolonged QTc intervals in the prone position and elevated APACHE II scores, with a relative risk of 10.75 (95% CI: 1.82–63.64, p = 0.008). Conclusions: The prone positioning caused minor yet significant changes in heart rate and QRS axis. The correlation of prolonged QTc intervals in the prone position with higher APACHE II scores suggests the prognostic relevance of prone ECG in COVID‐19 patients. However, further research is needed to fully understand the clinical implications and mechanisms of these findings. [ABSTRACT FROM AUTHOR]

In the last few years, a plethora of biomarkers have been proposed for the differentiation of Parkinson's disease (PD) from its mimics. Most of them consist of complex measures, often based on expensive technology, not easily employed outside research centers. MRI measures have been widely used to differentiate between PD and other parkinsonism. However, these measurements were often performed manually on small brain areas in small patient cohorts with intra- and inter-rater variability. The aim of the current review is to provide a comprehensive and updated overview of the literature on biomarkers commonly used to differentiate PD from its mimics (including parkinsonism and tremor syndromes), focusing on parameters derived by simple qualitative or quantitative measurements that can be used in routine practice. Several electrophysiological, sonographic and MRI biomarkers have shown promising results, including the blink-reflex recovery cycle, tremor analysis, sonographic or MRI assessment of substantia nigra, and several qualitative MRI signs or simple linear measures to be directly performed on MR images. The most significant issue is that most studies have been conducted on small patient cohorts from a single center, with limited reproducibility of the findings. Future studies should be carried out on larger international cohorts of patients to ensure generalizability. Moreover, research on simple biomarkers should seek measurements to differentiate patients with different diseases but similar clinical phenotypes, distinguish subtypes of the same disease, assess disease progression, and correlate biomarkers with pathological data. An even more important goal would be to predict the disease in the preclinical phase. [ABSTRACT FROM AUTHOR]

Disruptions in glutamate homeostasis within the mesolimbic reward circuitry may play a role in the pathophysiology of various reward related disorders such as major depressive disorders, anxiety, and substance use disorders. Clear sex differences have emerged in the rates and symptom severity of these disorders which may result from differing underlying mechanisms of glutamatergic signaling. Indeed, preclinical models have begun to uncover baseline sex differences throughout the brain in glutamate transmission and synaptic plasticity. Glutamatergic synaptic strength can be assessed by looking at morphological features of glutamatergic neurons including spine size, spine density, and dendritic branching. Likewise, electrophysiology studies evaluate properties of glutamatergic neurons to provide information of their functional capacity. In combination with measures of glutamatergic transmission, synaptic plasticity can be evaluated using protocols that induce long-term potentiation or long-term depression. This review will consider preclinical rodent literature directly comparing glutamatergic transmission and plasticity in reward related regions of males and females. Additionally, we will suggest which regions are exhibiting evidence for sexually dimorphic mechanisms, convergent mechanisms, or no sex differences in glutamatergic transmission and plasticity and highlight gaps in the literature for future investigation. [ABSTRACT FROM AUTHOR]

Measurement of the rate-dependent depression (RDD) of the Hoffmann (H) reflex, a technique developed over half a century ago, is founded on repeated stimulation of the H-reflex with tracking of sequentially evoked H-wave amplitudes in the resulting electromyogram. RDD offers insight into the integrity of spinal reflex pathways and spinal inhibitory regulation. Initially, RDD was predominantly utilized in the mechanistic exploration and evaluation of movement disorders characterized by spasticity symptoms, as may occur following spinal cord injury. However, there is increasing recognition that sensory input from the periphery is modified at the spinal level before ascending to the higher central nervous system and that some pain states can arise from, or be exaggerated by, disruption of spinal processing via a mechanism termed spinal disinhibition. This, along with the urgent clinical need to identify biological markers of pain generator and/or amplifier sites to facilitate targeted pain therapies, has prompted interest in RDD as a biomarker for the contribution of spinal disinhibition to neuropathic pain states. Current research in animals and humans with diabetes has revealed specific disorders of spinal GABAergic function associated with impaired RDD. Future investigations on RDD aim to further elucidate its underlying pathways and enhance its clinical applications.

Abstract Background In vitro models for drug testing constitute a valuable and simplified in-vivo-like assay to better comprehend the biological drugs effect. In particular, the combination of neuronal cultures with Micro-Electrode Arrays (MEAs) constitutes a reliable system to investigate the effect of drugs aimed at manipulating the neural activity and causing controlled changes in the electrophysiology. While chemical modulation in rodents’ models has been extensively studied in the literature, electrophysiological variations caused by chemical modulation on neuronal networks derived from human induced pluripotent stem cells (hiPSCs) still lack a thorough characterization. Methods In this work, we created three different configurations of hiPSCs-derived neuronal networks composed of fully glutamatergic neurons (100E), 75% of glutamatergic and 25% of GABAergic neurons (75E25I) and fully GABAergic neurons (100I). We focused on the effects caused by antagonists of three of the most relevant ionotropic receptors of the human brain, i.e., 2-amino-5-phosphonovaleric (APV, NMDA receptors antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, AMPA receptors antagonist), and bicuculline, picrotoxin and pentylenetetrazole (BIC, PTX, and PTZ, respectively, GABAA receptors antagonists). Results We found that APV and CNQX completely abolished the network bursting activity and caused major changes in the functional connectivity. On the other hand, the effect of BIC, PTX and PTZ mostly affected configurations in which the inhibitory component was present by increasing the firing and network bursting activity as well as the functional connectivity. Conclusions Our work revealed that hiPSCs-derived neuronal networks are very sensitive to pharmacological manipulation of the excitatory ionotropic glutamatergic and inhibitory ionotropic GABAergic transmission, representing a preliminary and necessary step forward in the field of drug testing that can rely on pathological networks of human origin.

Cardiac electrophysiology is a highly specialized field focused on the management of cardiac arrhythmias. Therefore, rigorous training is required for advanced practice providers (APPs) to competently practice independently within the specialty. An in-depth, 12-month training curriculum was created for electrophysiology in conjunction with a previously established APP Fellowship Program for the training of other complex subspecialties at an academic medical center. The Stanford Health Care Electrophysiology APP Fellowship Program is the first in the country to provide in-depth education and training for novice APPs to deliver high level care to patients with cardiac arrhythmias. The training program has proven to be successful in transitioning novice APPs to independent practitioners within the specialty since its inception in 2021.

Abstract Engineered biological neural networks are indispensable models for investigation of neural function and dysfunction from the subcellular to the network level. Notably, advanced neuroengineering approaches are of significant interest for their potential to replicate the topological and functional organization of brain networks. In this study, we reverse engineered feedforward neural networks of primary cortical and hippocampal neurons, using a custom-designed multinodal microfluidic device with Tesla valve inspired microtunnels. By interfacing this device with nanoporous microelectrodes, we show that the reverse engineered multinodal neural networks exhibit capacity for both segregated and integrated functional activity, mimicking brain network dynamics. To advocate the broader applicability of our model system, we induced localized perturbations with amyloid beta to study the impact of pathology on network functionality. Additionally, we demonstrate long-term culturing of subregion- and layer specific neurons extracted from the entorhinal cortex and hippocampus of adult Alzheimer’s-model mice and rats. Our results thus highlight the potential of our approach for reverse engineering of anatomically relevant multinodal neural networks to study dynamic structure-function relationships in both healthy and pathological conditions.

Grid cells in the entorhinal cortex demonstrate spatially periodic firing, thought to provide a spatial map on behaviorally relevant length scales. Whether such periodicity exists for behaviorally relevant time scales in the human brain remains unclear. We investigate neuronal firing during a temporally continuous experience by presenting 14 neurosurgical patients with a video while recording neuronal activity from multiple brain regions. We report on neurons that modulate their activity in a periodic manner across different time scales-from seconds to many minutes, most prevalently in the entorhinal cortex. These neurons remap their dominant periodicity to shorter time scales during a subsequent recognition memory task. When the video is presented at two different speeds, a significant percentage of these temporally periodic cells (TPCs) maintain their time scales, suggesting a degree of invariance. The TPCs temporal periodicity might complement the spatial periodicity of grid cells and together provide scalable spatiotemporal metrics for human experience.

Alzheimers disease (AD) is a chronic neurodegenerative disorder characterized by memory loss and progressive cognitive impairments. In mouse models of AD pathology, studies have found neuronal and synaptic deficits in hippocampus, but less is known about changes in medial entorhinal cortex (MEC), which is the primary spatial input to the hippocampus and an early site of AD pathology. Here, we measured neuronal intrinsic excitability and synaptic activity in MEC layer II (MECII) stellate cells, MECII pyramidal cells, and MEC layer III (MECIII) excitatory neurons at 3 and 10 months of age in the 3xTg mouse model of AD pathology, using male and female mice. At 3 months of age, before the onset of memory impairments, we found early hyperexcitability in intrinsic properties of MECII stellate and pyramidal cells, but this was balanced by a relative reduction in synaptic excitation (E) compared with inhibition (I; E/I ratio), suggesting intact homeostatic mechanisms regulating MECII activity. Conversely, MECIII neurons had reduced intrinsic excitability at this early time point with no change in synaptic E/I ratio. By 10 months of age, after the onset of memory deficits, neuronal excitability of MECII pyramidal cells and MECIII excitatory neurons was largely normalized in 3xTg mice. However, MECII stellate cells remained hyperexcitable, and this was further exacerbated by an increased synaptic E/I ratio. This observed combination of increased intrinsic and synaptic hyperexcitability suggests a breakdown in homeostatic mechanisms specifically in MECII stellate cells at this postsymptomatic time point, which may contribute to the emergence of memory deficits in AD.SIGNIFICANCE STATEMENT AD causes cognitive deficits, but the specific neural circuits that are damaged to drive changes in memory remain unknown. Using a mouse model of AD pathology that expresses both amyloid and tau transgenes, we found that neurons in the MEC have altered excitability. Before the onset of memory impairments, neurons in layer 2 of MEC had increased intrinsic excitability, but this was balanced by reduced inputs onto the cell. However, after the onset of memory impairments, stellate cells in MEC became further hyperexcitable, with increased excitability exacerbated by increased synaptic inputs. Thus, it appears that MEC stellate cells are uniquely disrupted during the progression of memory deficits and may contribute to cognitive deficits in AD.

Spatial cognition research requires behavioral paradigms that can distinguish between different navigational elements, such as allocentric (map-like) navigation and egocentric (e.g., body centered) navigation. To fill this need, we developed a flexible experimental platform that can be quickly modified without the need for significant changes to software and hardware. In this paper, we present this inexpensive and flexible behavioral platform paired with software which we are making freely available. Our behavioral platform serves as the foundation for a range of experiments, and although developed for assessing spatial cognition, it also has applications in the nonspatial domain of behavioral testing. There are two components of the software platform, Maze and Stim Trigger. While intended as a general platform, presently both programs can work in conjunction with Neuralynx and Open Ephys electrophysiology acquisition systems, allowing for precise time stamping of neural events. The Maze program includes functionality for automatic reward delivery based on user defined zones. Stim Trigger permits control of brain stimulation via any equipment that can be paired with an Arduino board. We seek to share our software and leverage the potential by expanding functionality in the future to meet the needs of a larger community of researchers.

AimsAtrial fibrillation (AF), the most prevalent clinical arrhythmia, is associated with atrial remodelling manifesting as acute and chronic alterations in expression, function, and regulation of atrial electrophysiological and Ca2+-handling processes. These AF-induced modifications crosstalk and propagate across spatial scales creating a complex pathophysiological network, which renders AF resistant to existing pharmacotherapies that predominantly target transmembrane ion channels. Developing innovative therapeutic strategies requires a systems approach to disentangle quantitatively the pro-arrhythmic contributions of individual AF-induced alterations.Methods and resultsHere, we built a novel computational framework for simulating electrophysiology and Ca2+-handling in human atrial cardiomyocytes and tissues, and their regulation by key upstream signalling pathways [i.e. protein kinase A (PKA), and Ca2+/calmodulin-dependent protein kinase II (CaMKII)] involved in AF-pathogenesis. Populations of atrial cardiomyocyte models were constructed to determine the influence of subcellular ionic processes, signalling components, and regulatory networks on atrial arrhythmogenesis. Our results reveal a novel synergistic crosstalk between PKA and CaMKII that promotes atrial cardiomyocyte electrical instability and arrhythmogenic triggered activity. Simulations of heterogeneous tissue demonstrate that this cellular triggered activity is further amplified by CaMKII- and PKA-dependent alterations of tissue properties, further exacerbating atrial arrhythmogenesis.ConclusionsOur analysis reveals potential mechanisms by which the stress-associated adaptive changes turn into maladaptive pro-arrhythmic triggers at the cellular and tissue levels and identifies potential anti-AF targets. Collectively, our integrative approach is powerful and instrumental to assemble and reconcile existing knowledge into a systems network for identifying novel anti-AF targets and innovative approaches moving beyond the traditional ion channel-based strategy.

Prior studies suggest that habituation of sensory responses is reduced in autism and that diminished habituation could be related to atypical autistic sensory experiences, for example, by causing brain responses to aversive stimuli to remain strong over time instead of being suppressed. While many prior studies exploring habituation in autism have repeatedly presented identical stimuli, other studies suggest group differences can still be observed in habituation to intermittent stimuli. The present study explored habituation of electrophysiological responses to auditory complex tones of varying intensities (50-80 dB SPL), presented passively in an interleaved manner, in a well-characterized sample of 127 autistic (MDQ  = 65.41, SD = 20.54) and 79 typically developing (MDQ  = 106.02, SD = 11.50) children between 2 and 5 years old. Habituation was quantified as changes in the amplitudes of single-trial responses to tones of each intensity over the course of the experiment. Habituation of the auditory N2 response was substantially reduced in autistic participants as compared to typically developing controls, although diagnostic groups did not clearly differ in habituation of the P1 response. Interestingly, the P1 habituated less to loud 80 dB sounds than softer sounds, whereas the N2 habituated less to soft 50 dB sounds than louder sounds. No associations were found between electrophysiological habituation and cognitive ability or participants' caregiver-reported sound tolerance (Sensory Profile Hyperacusis Index). The results present study results extend prior research suggesting habituation of certain sensory responses is reduced in autism; however, they also suggest that habituation differences observed using this study's paradigm might not be a primary driver of autistic participants' real-world sound intolerance.

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. [ABSTRACT FROM AUTHOR]

Both alcohol use disorder (AUD) and cognitive decline include disruption in the balance of excitation and inhibition in the cortex, but the potential role of alcohol use on excitation and inhibition on the aging brain is unclear. We examined the effect of moderate voluntary binge alcohol consumption on the aged, pre-disease neuronal environment by measuring intrinsic excitability and spontaneous neurotransmission on prefrontal cortical pyramidal (excitatory, glutamatergic) and non-pyramidal (inhibitory, GABAergic) neurons following a prolonged period of abstinence from alcohol in mice. Results highlight that binge alcohol consumption has lasting impacts on the electrophysiological properties of prefrontal cortical neurons. A profound increase in excitatory events onto layer 2/3 non-pyramidal neurons following alcohol consumption was seen, along with altered intrinsic excitability of pyramidal neurons, which could have a range of effects on cognitive disorder progression, such as Alzheimer's Disease, in humans. These results indicate that moderate voluntary alcohol influences the pre-disease environment in aging and highlight the need for further mechanistic investigation into this risk factor. [Display omitted] • Moderate voluntary alcohol disrupts prefrontal cortical signaling at protracted ages in mice. • Glutamatergic events onto GABA neurons are increased 6 months following alcohol exposure. • Pyramidal and GABA neurons show altered intrinsic excitability 6 months after alcohol exposure. [ABSTRACT FROM AUTHOR]

Background: Increasingly valuable, sophisticated, and powerful aircraft are developed and incorporated into the armed forces. Technological advances are notable for increasing physiological load during the flight, making human resources a limiting factor in such operations. It is necessary to understand the physiological demands to which aircraft pilots are exposed, especially combat pilots. Objective: This study aimed to present: i. the physiological consequences on the human body due to high accelerative forces during high-performance flights; ii. the efficiency of the Anti-G Straining Maneuver (AGSM) countermeasure to such consequences; and iii. the state of the art about surface electromyography's uses (sEMG) in AGSM. Method: It was conducted a bibliographic search in the PubMed database using the keywords “anti-G effort maneuver” and “electromyography” and their synonyms. After this, a narrative review of the results was performed. This research model allows a comprehensive discussion about the topic, enabling an in-depth contextualization in a prosperous field of study. These characteristics are suitable for detecting literature gaps and directing the research discussion. Discussion: There is a consensus in the literature that AGSM is the most effective resource to prevent loss of consciousness induced by G-load (G-LOC). The sEMG is an affordable and useful tool for AGSM training, especially given the unavailability of human centrifuges. The current literature on the application of sEMG in the context of AGSM training is limited, presenting a diversity of objectives, methodology, and analyzed parameters. Conclusion: The use of sEMG as real-time biofeedback can improve the pilot's muscle control skills during AGSM.

The global health concern of pharmacoresistant epilepsy necessitates innovative therapeutic strategies. Drug resistance often arises due to complex pharmacokinetic challenges. Beta-cyclodextrin, known for enhancing drug solubility and stability, offers a potential solution for improving the efficacy of antiseizure medications. This study aims to investigate the impact of beta-cyclodextrin-complexed rufinamide on seizure-like activity using an in vitro model of temporal lobe epilepsy.

Robotic technology is one of the most dynamically evolving fields in medicine. Alongside technological advancement, there is a growing demand for automated functions aimed at preventing human errors. The application of robotic technologies in cardiology, especially in electrophysiology, is becoming increasingly widespread. Robots enable more precise and safer interventions, overcoming the limitations of manual methods. This review primarily focuses on describing the most widely available cardiac robotic technology at present, the robotic magnetic navigation system (RMN). The RMN system offers numerous advantages during catheter ablation procedures, including reduced fluoroscopy exposure, decreased incidence of complications, and improved acute and long-term success rates. RMN is a valuable tool in the treatment of complex arrhythmias, as well as in patients with congenital heart defects or those who have undergone previous surgical interventions. Its exceptional image integration capabilities and precise catheter navigation offer a safe and effective solution in the field of electrophysiology.

Abstract Introduction Closed-loop spinal cord stimulation (CL-SCS) is a recently introduced system that records evoked compound action potentials (ECAPs) from the spinal cord elicited by each stimulation pulse and uses this information to automatically adjust the stimulation strength in real time, known as ECAP-controlled SCS. This innovative system compensates for fluctuations in the distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a predetermined target level. This data collection study was designed to assess the performance of the first CL-SCS system in a real-world setting under normal conditions of use in multiple European centers. The study analyzes and presents clinical outcomes and electrophysiological and device data and compares these findings with those reported in earlier pre-market studies of the same system. Methods This prospective, multicenter, observational study was conducted in 13 European centers and aimed to gather electrophysiological and device data. The study focused on the real-world application of this system in treating chronic pain affecting the trunk and/or limbs, adhering to standard conditions of use. In addition to collecting and analyzing basic demographic information, the study presents data from the inaugural patient cohort permanently implanted at multiple European centers. Results A significant decrease in pain intensity was observed for overall back or leg pain scores (verbal numerical rating score [VNRS]) between baseline (mean ± standard error of the mean [SEM]; n = 135; 8.2 ± 0.1), 3 months (n = 93; 2.3 ± 0.2), 6 months (n = 82; 2.5 ± 0.3), and 12 months (n = 76; 2.5 ± 0.3). Comparison of overall pain relief (%) to the AVALON and EVOKE studies showed no significant differences at 3 and 12 months between the real-world data release (RWE; 71.3%; 69.6%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies. Further investigation was undertaken to objectively characterize the physiological parameters of SCS therapy in this cohort using the metrics of percent time above ECAP threshold (%), dose ratio, and dose accuracy (µV), according to previously described methods. Results showed that a median of 90% (40.7–99.2) of stimuli were above the ECAP threshold, with a dose ratio of 1.3 (1.1–1.4) and dose accuracy of 4.4 µV (0.0–7.1), based on data from 236, 230, and 254 patients, respectively. Thus, across all three metrics, the majority of patients had objective therapy metrics corresponding to the highest levels of pain relief in previously reported studies (usage over threshold > 80%, dose ratio > 1.2, and error

Functional tremor is the most common subtype of functional movement disorder (FMD). At present, there is no "gold standard" for diagnosis. Most clinical manifestations coincide with organic tremor, which can easily lead to misdiagnosis and mistreatment. Characteristic electrophysiological manifestations can provide objective and repeatable diagnostic information, effectively supplement the history and physical examination, and can also be used in the differential diagnosis from organic tremor. This article reviews the electrophysiological characteristics of functional tremor and its application in diagnosis and differential diagnosis, in order to improve the clinical understanding of this disease.

Abstract The red palm weevil (RPW), Rhynchophorus ferrugineus (Olivier), also known as the Asian palm weevil, is an invasive pest that causes widespread damage to palm trees around the globe. As pheromone communication is crucial for their mass attack and survival on palm trees, the olfactory concept of pest control strategies has been widely explored recently. We aim to understand the molecular basis of olfaction in RPW by studying one of the key olfactory proteins in insect pheromone communication, sensory neuron membrane proteins (SNMPs). SNMPs belong to the CD36 (cluster of differentiation 36) family that perform two distinct olfactory roles in insects, either in pheromone (odorant) transfer to the odorant receptors (SNMP1) or in the pheromone clearing process (SNMP2). In this study, we performed antennal transcriptomic screening and identified six SNMPs, mapping them on the R. ferrugineus genome, and confirmed four distinct SNMPs. Both SNMP1 proteins in RPW, viz., RferSNMPu1 and RferSNMPu2, were mapped onto the same scaffold in different loci in the RPW genome. To further understand the function of these proteins, we first classified them using phylogenetic analysis and checked their tissue-specific expression patterns. Further, we measured the relative transcript abundance of SNMPs in laboratory-reared, field-collected adults and pheromone-exposure experiments, ultimately identifying RferSNMPu1 as a potential candidate for functional analysis. We mapped RferSNMPu1 expression in the antennae and found that expression patterns were similar in both sexes. We used RNAi-based gene silencing to knockdown RferSNMPu1 and tested the changes in the RPW responses to aggregation pheromone compounds, 4-methyl-5-nonanol (ferrugineol) and 4-methyl-5-nonanone (ferrugineone), and a kairomone, ethyl acetate using electroantennogram (EAG) recordings. We found a significant reduction in the EAG recordings in the RferSNMPu1 knockdown strain of adult RPWs, confirming its potential role in pheromone detection. The structural modelling revealed the key domains in the RferSNMPu1 structure, which could likely be involved in pheromone detection based on the identified ectodomain tunnels. Our studies on RferSNMPu1 with a putative role in pheromone detection provide valuable insight into understanding the olfaction in R. ferrugineus as well as in other Curculionids, as SNMPs are under-explored in terms of its functional role in insect olfaction. Most importantly, RferSNMPu1 can be used as a potential target for the olfactory communication disruption in the R. ferrugineus control strategies.

Abstract Background The transition from childhood to adulthood, or adolescence, a developmental stage, is characterized by psychosocial and biological changes. The nucleus accumbens (NAc), a striatal brain region composed of the core (NAcC) and shell (NAcSh), has been linked to risk-taking behavior and implicated in reward seeking and evaluation. Most neurons in the NAc are medium spiny neurons (MSNs) that express dopamine D1 receptors (D1R +) and/or dopamine D2 receptors (D2R +). Changes in dopaminergic and glutamatergic systems occur during adolescence and converge in the NAc. While there are previous investigations into sex differences in membrane excitability and synaptic glutamate transmission in both subdivisions of the NAc, to our knowledge, none have specified NAcSh D1R + MSNs from mice during pre- and mid-adolescence. Methods Sagittal brain slices containing the NAc were prepared from B6.Cg-Tg(Drd1a-tdTomato)6Calak/J mice of both sexes from postnatal days 21–25 and 35–47, representing pre- and mid-adolescence, respectively. Whole-cell electrophysiology recordings were collected from NAcSh D1R + MSNs in the form of membrane-voltage responses to current injections, to assess membrane properties and action potential waveform characteristics, and spontaneous excitatory postsynaptic currents (sEPSCs) to assess glutamatergic synaptic activity. Results Relative to pre-adolescent males, pre-adolescent female NAcSh D1R + MSNs exhibited a less hyperpolarized resting membrane potential, increased input resistance, and smaller action potential afterhyperpolarization amplitudes. During mid-adolescence, decreased input resistance and a shorter action potential duration in females were the only sex differences observed. Conclusions Taken together, our results indicate that NAcSh D1R + MSNs in mice exhibit sex differences in membrane properties and AP waveform during pre-adolescence that are overall indicative of increased cellular excitability in females and are suggestive of possible sex differences in glycine receptors, inwardly-rectifying potassium channels, and large conductance voltage-gated potassium channels. These differences do not appear to persist into mid-adolescence, when sex was observed to affect input resistance oppositely to that of pre-adolescence and AP waveform in a manner suggestive of differences in voltage-gated potassium channels.

Abstract Background Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy with multifactorial etiologies. We intended in this case–control study to identify, out of a comprehensive set of risk factors, the relatively important ones and develop a quantitative risk assessment model for this disorder. It was also legitimate to define the hazard of those factors in a dose-related manner and the acceptable safe limit especially for work-related stresses. Results Age and female predominance were comparable between the 60 patients (89 hands with electrophysiologically confirmed CTS) and 50 controls (100 hands). Occupation of the studied sample varied between housewives only, employed housewives, and manual workers with a distribution that differed significantly between patients and controls. Significantly higher body mass index (BMI) and mean wrist depth were found in patients than controls. Wrist ratio (clinically or sonographically) was significantly squarer in patients than controls. Overall workload and number of hours spent daily performing work with repeated hand movements or awkward hand position were significantly higher among patients than controls. ROC curves were constructed for wrist measurements and occupational stresses. Cut-off points of wrist ratio and internal carpal tunnel ratio (by ultrasound) to discriminate subjects with CTS were > 0.68 and ≤ 1.854, respectively. The best cut-off value for number of hours spent daily performing work with repeated hand movements was 3 h/ day. As for working with awkward hand position or cold exposure, cut-off value was 0.6 h/day for both. Two logistic regression models were conducted to investigate nonoccupational and occupational predictors of CTS. The independent predictors concluded from the first model were BMI, positive family history of CTS, wrist ratio, and decrease grip strength. As for the occupational model, predictors were tasks requiring awkward hand position and cold exposure. Conclusion Occupational risk assessment by clinical, anthropometric, and ultrasonographic measurement should be used in professions requiring repetitive or awkward hand movements, so that in overweight persons with square wrists appropriate workplace setup measures or assistive technology at work or home could be taken to prevent or decrease the impact of work hazards or help choose individuals with low risk for appropriate jobs.

Abstract The flicker stimulus is a visual stimulus of intermittent illumination. A flicker stimulus can appear flickering or steady to a human subject, depending on the physical parameters associated with the stimulus. When the flickering light appears steady, flicker fusion is said to have occurred. This work aims to bridge the gap between the psychophysics of flicker fusion and the electrophysiology associated with flicker stimulus through a Deep Learning based computational model of flicker perception. Convolutional Recurrent Neural Networks (CRNNs) were trained with psychophysics data of flicker stimulus obtained from a human subject. We claim that many of the reported features of electrophysiology of the flicker stimulus, including the presence of fundamentals and harmonics of the stimulus, can be explained as the result of a temporal convolution operation on the flicker stimulus. We further show that the convolution layer output of a CRNN trained with psychophysics data is more responsive to specific frequencies as in human EEG response to flicker, and the convolution layer of a trained CRNN can give a nearly sinusoidal output for 10 hertz flicker stimulus as reported for some human subjects.

Invasive and non-invasive electrophysiological measurements during "cocktail-party"-like listening indicate that neural activity in the human auditory cortex (AC) "tracks" the envelope of relevant speech. However, due to limited coverage and/or spatial resolution, the distinct contribution of primary and non-primary areas remains unclear. Here, using 7-Tesla fMRI, we measured brain responses of participants attending to one speaker, in the presence and absence of another speaker. Through voxel-wise modeling, we observed envelope tracking in bilateral Heschl's gyrus (HG), right middle superior temporal sulcus (mSTS) and left temporo-parietal junction (TPJ), despite the signal's sluggish nature and slow temporal sampling. Neurovascular activity correlated positively (HG) or negatively (mSTS, TPJ) with the envelope. Further analyses comparing the similarity between spatial response patterns in the single speaker and concurrent speakers conditions and envelope decoding indicated that tracking in HG reflected both relevant and (to a lesser extent) non-relevant speech, while mSTS represented the relevant speech signal. Additionally, in mSTS, the similarity strength correlated with the comprehension of relevant speech. These results indicate that the fMRI signal tracks cortical responses and attention effects related to continuous speech and support the notion that primary and non-primary AC process ongoing speech in a push-pull of acoustic and linguistic information. The tracking of continuous speech is examined with high-field fMRI. In two-speaker scenes, speech tracking of the BOLD signal suggests distinct roles of Heschl's gyrus and superior temporal sulcus for processing relevant and non-relevant speech. [ABSTRACT FROM AUTHOR]

Background: The study explored the differences in audiological and non-audiological characteristics between congenital, early-onset, and late-onset auditory neuropathy spectrum disorder (ANSD). Ninety-five individuals diagnosed with ANSD were included in the study. They were divided into three groups congenital ANSD—children (30 individuals, 60 ears), adults with early-onset ANSD (30 individuals, 56 ears), and adults with late-onset ANSD (35 individuals, 62 ears). The non-audiological characteristics (gender, laterality, and risk factors) and audiological characteristics (behavioral and electrophysiological measures) were compared between the three groups. Results: Discriminant analyses showed that the pure tone average, audiogram configuration, and speech thresholds were the best auditory predictors of onset-based group differences in ANSD (congenital and early-onset versus late-onset ANSD). While the congenital and early-onset group showed poorer pure-tone and speech thresholds, along with flat configuration, the late-onset group demonstrated relatively better thresholds and other configurations (rising, tent-shaped, cookie-bite). In addition, long latency responses were delayed or absent in children with congenital ANSD, indicative of onset coding deficits at the cortical level. Conclusions: The study highlights the audiological differences between congenital, early-, and late-onset ANSD groups. These differences could be because of variations in etiology, pathophysiology, site of lesion, or genetic variability between the groups, which needs to be explored further. [ABSTRACT FROM AUTHOR]

The role of the cerebellum in emotional control has gained increasing interest, with studies showing it is involved in fear learning and memory in both humans and rodents. This review will focus on the contributions of the cerebellum to the extinction of learned fear responses. Extinction of fearful memories is critical for adaptive behaviour, and is clinically relevant to anxiety disorders such as post-traumatic stress disorder, in which deficits in extinction processes are thought to occur. We present evidence that supports cerebellar involvement in fear extinction, from rodent studies that investigate molecular mechanisms and functional connectivity with other brain regions of the known fear extinction network, to fMRI studies in humans. This evidence is considered in relation to the theoretical framework that the cerebellum is involved in the formation and updating of internal models of the inner and outer world by detecting errors between predicted and actual outcomes. In the case of fear conditioning, these internal models are thought to predict the occurrence of an aversive unconditioned stimulus (US), and when the aversive US is unexpectedly omitted during extinction learning the cerebellum uses prediction errors to update the internal model. Differences between human and rodent studies are highlighted to help inform future work. [ABSTRACT FROM AUTHOR]

Bioelectronic medicine is emerging as a powerful approach for restoring lost endogenous functions and addressing life‐altering maladies such as cardiac disorders. Systems that incorporate both modulation of cellular function and recording capabilities can enhance the utility of these approaches and their customization to the needs of each patient. Here we report an integrated optogenetic and bioelectronic platform for stable and long‐term stimulation and monitoring of cardiomyocyte function in vitro. Optical inputs are achieved through the expression of a photoactivatable adenylyl cyclase, that when irradiated with blue light causes a dose‐dependent and time‐limited increase in the secondary messenger cyclic adenosine monophosphate with subsequent rise in autonomous cardiomyocyte beating rate. Bioelectronic readouts are obtained through a multi‐electrode array that measures real‐time electrophysiological responses at 32 spatially‐distinct locations. Irradiation at 27 µW mm−2 results in a 14% elevation of the beating rate within 20–25 min, which remains stable for at least 2 h. The beating rate can be cycled through "on" and "off" light states, and its magnitude is a monotonic function of irradiation intensity. The integrated platform can be extended to stretchable and flexible substrates, and can open new avenues in bioelectronic medicine, including closed‐loop systems for cardiac regulation and intervention, for example, in the context of arrythmias. [ABSTRACT FROM AUTHOR]

Summary Previous studies indicated that patients with isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) exhibit alterations in spectral electroencephalographic (EEG), spindle, and slow‐wave features. As it is currently unknown how these EEG features evolve over time, this study aimed to evaluate their temporal progression in patients with iRBD in comparison to controls. We included 23 patients with iRBD and 23 controls. Two polysomnographies (baseline and follow‐up) were recorded with a mean (standard deviation) interval of 4.0 (2.5) years and were automatically analysed for sleep stages, spectral bandpower, spindles, and slow waves. We used linear models to evaluate differences at each time point, and linear mixed‐effects models to analyse differences in temporal progression between the groups. At baseline, patients with iRBD presented EEG slowing both in REM (expressed as significantly reduced α‐bandpower and increased δ‐bandpower in frontal channels) and in non‐REM (NREM) sleep (significantly increased slow‐to‐fast ratio in central channels). These differences vanished at follow‐up. In both REM and NREM sleep, γ‐bandpower was increased at follow‐up in patients with iRBD, resulting in significantly different temporal progression between groups (in occipital channels during REM sleep and frontal channels during NREM sleep). Relative power of sleep spindles was significantly higher at baseline in patients with iRBD in frontal channels, but we observed a significant reduction over time in central channels. Finally, slow waves were significantly shorter in patients with iRBD at both time‐points. Our results underscore the need of considering longitudinal data when analysing sleep EEG features in patients with iRBD. The observed temporal changes as markers of progression of neurodegeneration require further investigations. [ABSTRACT FROM AUTHOR]

The visual search for product packaging involves intricate cognitive processes that are prominently impacted by learned associations derived from extensive long-term experiences. The present research employed EEG technology and manipulated the color display of reference pictures on beverage bottles to explore the underlying neurocognitive pathways. Specifically, we aimed to investigate the influence of color-flavor association strength on the visual processing of such stimuli as well as the in-depth neural mechanisms. The behavioral results revealed that stimuli with strong association strength triggered the fastest response and the highest accuracy, compared with the stimuli with weak association strength and the achromatic ones. The EEG findings further substantiated that the chromatic stimuli evoked a more pronounced N2 component than achromatic ones, and the stimuli with strong association strength elicited larger P3 and smaller N400 amplitudes than the ones with weak association strength. Additionally, the source localization using sLORETA showed significant activations in the inferior temporal gyrus. In conclusion, our research suggests that (1) color expectations would guide visual search process and trigger faster responses to congruent visual stimuli, (2) both the initial perceptual representation and subsequent semantic representation play pivotal roles in effective visual search for the targets, and (3) the colorflavor association strength potentially exerts an impact on visual processing by modulating memory accessibility. [ABSTRACT FROM AUTHOR]

Ithildin is an open-source library and framework for efficient parallelized simulations of excitable media, written in the C++ programming language. It uses parallelization on multiple CPU processors via the message passing interface (MPI). We demonstrate the library's versatility through a series of simulations in the context of the monodomain description of cardiac electrophysiology, including the S1S2 protocol, spiral break-up, and spiral waves in ventricular geometry. Our work demonstrates the power of Ithildin as a tool for studying complex wave patterns in cardiac tissue and its potential to inform future experimental and theoretical studies. We publish our full code with this paper in the name of open science. [ABSTRACT FROM AUTHOR]

The electrophysiological interface is essential for understanding electrical activities within biological organisms and human‐machine interaction. However, traditional preformed bioelectrodes show insufficient interface contact with hairy and irregular skin, causing signal attenuation and distortion. Here, an on‐skin‐formed silk protein bioelectrode is reported with a conformable and robust interface, achieving a high signal‐to‐noise ratio for electromyographic signals, showing up to a 38.9% increase compared to traditional ones. The fluid‐gel transition of silk protein is induced by a gelling agent composed of ethanol and sodium alginate, leading to a conformable and seamless interface with hairy and irregular human skin, thus resulting in a high signal‐to‐noise ratio. The developed bioelectrode can record electrophysiological signals stably, even underwater. Additionally, human‐machine interaction using electromyographic signals is designed to precisely control the model car's motion trajectory. This work presents an effective method for developing a seamless and conformable electrophysiological interface in bioelectronics. [ABSTRACT FROM AUTHOR]

Different speeds of locomotion require heterogeneous spinal populations, but a common mode of rhythm generation is presumed to exist. Here, we explore the cellular versus synaptic origins of spinal rhythmicity at different speeds by performing electrophysiological recordings from premotor excitatory interneurons in larval zebrafish. Chx10-labeled V2a neurons are divided into at least two morphological subtypes proposed to play distinct roles in timing and intensity control. Consistent with distinct rhythm generating and output patterning functions within the spinal V2a population, we find that descending subtypes are recruited exclusively at slow or fast speeds and exhibit intrinsic cellular properties suitable for rhythmogenesis at those speeds, while bifurcating subtypes are recruited more reliably at all speeds and lack appropriate rhythmogenic cellular properties. Unexpectedly, however, phasic firing patterns during locomotion in rhythmogenic and non-rhythmogenic V2a neurons alike are best explained by distinct modes of synaptic inhibition linked to cell type and speed. At fast speeds reciprocal inhibition in descending V2a neurons supports phasic firing, while recurrent inhibition in bifurcating V2a neurons helps pattern motor output. In contrast, at slow speeds recurrent inhibition in descending V2a neurons supports phasic firing, while bifurcating V2a neurons rely on reciprocal inhibition alone to pattern output. Our findings suggest cell-type-specific, not common, modes of rhythmogenesis generate and coordinate different speeds of locomotion. [ABSTRACT FROM AUTHOR]

Summary This article aims at providing a comprehensive review of the historical discovery and following research on rapid eye movement (REM) sleep, highlighting its manifold nature as a behavioural, electrophysiological and dreaming state. Pioneering works conducted by Aserinsky, Kleitman, Dement and Jouvet established the foundational understanding of REM sleep recurrence, brainstem mechanisms, and the paradoxical coexistence of electroencephalographic activation and muscle atonia. We focus on REM sleep homeostasis, emphasising its role in emotional recovery and the consequences of REM deprivation, such as the REM rebound effect. We also analyse the periodicity of REM sleep, its ultradian rhythm, and the physiological mechanisms underlying its regulation. Additionally, the article discusses the entangled relationship between arousals, sleep, and consciousness, pointing out the distinction between non‐REM and REM sleep‐related arousals, and the similarities between REM sleep and wakefulness. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer (NSCLC) accounts for 80–85% of primary lung cancers. Radiation therapy is widely used to treat both primary NSCLC and lung cancer that has spread to the brain. However, radiotherapy responses are not durable and toxicity limits therapy. Therefore, there is an urgent need for new agents that can enhance the effectiveness of radiation therapy in lung cancer and reduce its toxicity. We find that AM-101, a benzodiazepine analog, enhances the effects of radiation and significantly improves the survival of mice with lung cancer brain-metastatic tumors. Additionally, AM-101 makes radiation treatment work better and slows down the growth of NSCLC subcutaneous xenograft tumors in mice. AM-101 activates the GABA(A) receptor in lung cancer cells, triggering selective autophagy by causing GABARAP to form multimers and stabilizing the mitochondrial receptor Nix. GABA(A) receptor activation may improve tumor control and allow for lower radiation doses, reducing toxicity. In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability and clonogenicity of both primary and brain-metastatic NSCLC cells. Employing a human-relevant ex vivo 'chip', AM-101 is as efficacious as docetaxel, a chemotherapeutic used with radiotherapy for advanced-stage NSCLC. In vivo, AM-101 potentiates radiation, including conferring a significant survival benefit to mice bearing NSCLC intracranial tumors generated using a patient-derived metastatic line. GABA(A) receptor activation stimulates a selective-autophagic response via the multimerization of GABA(A) receptor-associated protein, GABARAP, the stabilization of mitochondrial receptor Nix, and the utilization of ubiquitin-binding protein p62. A high-affinity peptide disrupting Nix binding to GABARAP inhibits AM-101 cytotoxicity. This supports a model of GABA(A) receptor activation driving a GABARAP–Nix multimerization axis that triggers autophagy. In patients receiving radiotherapy, GABA(A) receptor activation may improve tumor control while allowing radiation dose de-intensification to reduce toxicity. [ABSTRACT FROM AUTHOR]

As atrial fibrillation (AF) progresses from initial paroxysmal episodes to the persistent phase, maintaining sinus rhythm for an extended period through pharmacotherapy and catheter ablation becomes difficult. A major cause of the deteriorated treatment outcome is the atrial structural and electrophysiological heterogeneity, which AF itself can exacerbate. This heterogeneity exists or manifests in various dimensions, including anatomically segmental structural features, the distribution of histological fibrosis and the autonomic nervous system, sarcolemmal ion channels, and electrophysiological properties. All these types of heterogeneity are closely related to the development of AF. Recognizing the heterogeneity provides a valuable approach to comprehending the underlying mechanisms in the complex excitatory patterns of AF and the determining factors that govern the seemingly chaotic propagation. Furthermore, substrate modification based on heterogeneity is a potential therapeutic strategy. This review aims to consolidate the current knowledge on structural and electrophysiological atrial heterogeneity and its relation to the pathogenesis of AF, drawing insights from clinical studies, animal and cell experiments, molecular basis, and computer-based approaches, to advance our understanding of the pathophysiology and management of AF. [ABSTRACT FROM AUTHOR]

The human heart is subject to highly variable amounts of strain during day‐to‐day activities and needs to adapt to a wide range of physiological demands. This adaptation is driven by an autoregulatory loop that includes both electrical and the mechanical components. In particular, mechanical forces are known to feed back into the cardiac electrophysiology system, which can result in pro‐ and anti‐arrhythmic effects. Despite the widespread use of computational modelling and simulation for cardiac electrophysiology research, the majority of in silico experiments ignore this mechano‐electric feedback entirely due to the high computational cost associated with solving cardiac mechanics. In this study, we therefore use an electromechanically coupled whole‐heart model to investigate the differential and combined effects of electromechanical feedback mechanisms with a focus on their physiological relevance during sinus rhythm. In particular, we consider troponin‐bound calcium, the effect of deformation on the tissue diffusion tensor, and stretch‐activated channels. We found that activation of the myocardium was only significantly affected when including deformation into the diffusion term of the monodomain equation. Repolarization, on the other hand, was influenced by both troponin‐bound calcium and stretch‐activated channels and resulted in steeper repolarization gradients in the atria. The latter also caused afterdepolarizations in the atria. Due to its central role for tension development, calcium bound to troponin affected stroke volume and pressure. In conclusion, we found that mechano‐electric feedback changes activation and repolarization patterns throughout the heart during sinus rhythm and lead to a markedly more heterogeneous electrophysiological substrate. Key points: The electrophysiological and mechanical function of the heart are tightly interrelated by excitation–contraction coupling (ECC) in the forward direction and mechano‐electric feedback (MEF) in the reverse direction.While ECC is considered in many state‐of‐the‐art computational models of cardiac electromechanics, less is known about the effect of different MEF mechanisms.Accounting for calcium bound to troponin increases stroke volume and delays repolarization. Geometry‐mediated MEF leads to more heterogeneous activation and repolarization with steeper gradients. Both effects combine in an additive way.Non‐selective stretch‐activated channels as an additional MEF mechanism lead to heterogeneous diastolic transmembrane voltage, higher developed tension and delayed repolarization or afterdepolarizations in highly stretched parts of the atria.The differential and combined effects of these three MEF mechanisms during sinus rhythm activation in a human four‐chamber heart model may have implications for arrhythmogenesis, both in terms of substrate (repolarization gradients) and triggers (ectopy). [ABSTRACT FROM AUTHOR]

Cardiac electrophysiology and mechanics are strongly interconnected. Their interaction is, among others, mediated by mechano‐electric feedback through stretch‐activated ion channels (SACs). The electrophysiological changes induced by SACs may contribute to arrhythmogenesis, but the precise SAC‐induced electrophysiological changes remain incompletely understood. Here, we provide a systematic characterization of stretch effects through three distinguished SACs on cardiac electrophysiology using computational modelling. We implemented potassium‐selective, calcium‐selective and non‐selective SACs in the Tomek–Rodriguez–O'Hara–Rudy model of human ventricular electrophysiology. The model was calibrated to experimental data from isolated cardiomyocytes undergoing stretch, considering inter‐species differences, and disease‐related remodelling of SACs. SAC‐mediated effects on the action potential (AP) were analysed by varying stretch amplitude, application timing and/or duration. Afterdepolarizations of different amplitudes were observed with transient 10‐ms stretch stimuli of 15–18% applied during phase 4, while stretch ≥18% during phase 4 elicited triggered APs. Longer stimuli shifted the threshold of AP trigger during phase 4 to lower amplitudes, while shorter stimuli increased it. Continuous stretch provoked electrophysiological remodelling. Furthermore, stretch shortened duration or changed morphology of a subsequent electrically evoked AP, and, if applied during a vulnerable time window with sufficient amplitude, prevented its occurrence because of stretch‐induced modulation of sodium and L‐type calcium channel gating. These effects were more pronounced with disease‐related SAC remodelling due to increased stretch sensitivity of diseased hearts. We showed that SACs may induce afterdepolarizations and triggered activities, and prevent subsequent AP generation or change its morphology. These effects depend on cardiomyocyte stretch characteristics and disease‐related SACs remodelling and may contribute to cardiac arrhythmogenesis. Key points: The interplay between cardiac electrophysiology and mechanics is mediated by mechano‐electric feedback through stretch‐activated ion channels (SACs). These channels may be pro‐arrhythmic, but their precise effect on electrophysiology remains unclear.Here we present a systematic in silico characterization of stretch effects through three SACs by implementing inter‐species differences as well as disease‐related remodelling of SACs in a novel computational model of human ventricular cardiomyocyte electrophysiology.Our simulations showed that, at the cellular level, SACs may provoke electrophysiological remodelling, afterdepolarizations, triggered activities, change the morphology or shorten subsequent electrically evoked action potentials. The model further suggests that a vulnerable window exists in which stretch prevents the following electrically triggered beat occurrence.The pro‐arrhythmic effects of stretch strongly depend on disease‐related SAC remodelling as well as on stretch characteristics, such as amplitude, time of application and duration. Our study helps in understanding the role of stretch in cardiac arrhythmogenesis and revealing the underlying cellular mechanisms. [ABSTRACT FROM AUTHOR]

Mechano‐electric regulations (MER) play an important role in the maintenance of cardiac performance. Mechano‐calcium and mechano‐electric feedback (MCF and MEF) pathways adjust the cardiomyocyte contractile force according to mechanical perturbations and affects electro‐mechanical coupling. MER integrates all these regulations in one unit resulting in a complex phenomenon. Computational modelling is a useful tool to accelerate the mechanistic understanding of complex experimental phenomena. We have developed a novel model that integrates the MER loop for human atrial cardiomyocytes with proper consideration of feedforward and feedback pathways. The model couples a modified version of the action potential (AP) Koivumäki model with the contraction model by Quarteroni group. The model simulates iso‐sarcometric and isometric twitches and the feedback effects on AP and Ca2+‐handling. The model showed a biphasic response of Ca2+ transient (CaT) peak to increasing pacing rates and highlights the possible mechanisms involved. The model has shown a shift of the threshold for AP and CaT alternans from 4.6 to 4 Hz under post‐operative atrial fibrillation, induced by depressed SERCA activity. The alternans incidence was dependent on a chain of mechanisms including RyRs availability time, MCF coupling, CaMKII phosphorylation, and the stretch levels. As a result, the model predicted a 10% slowdown of conduction velocity for a 20% stretch, suggesting a role of stretch in creation of substrate formation for atrial fibrillation. Overall, we conclude that the developed model provides a physiological CaT followed by a physiological twitch. This model can open pathways for the future studies of human atrial electromechanics. Key points: With the availability of human atrial cellular data, interest in atrial‐specific model integration has been enhanced.We have developed a detailed mathematical model of human atrial cardiomyocytes including the mechano‐electric regulatory loop. The model has gone through calibration and evaluation phases against a wide collection of available human in‐vitro data.The usefulness of the model for analysing clinical problems has been preliminaryly tested by simulating the increased incidence of Ca2+ transient and action potential alternans at high rates in post‐operative atrial fibrillation condition.The model determines the possible role of mechano‐electric feedback in alternans incidence, which can increase vulnerability to atrial arrhythmias by varying stretch levels.We found that our physiologically accurate description of Ca2+ handling can reproduce many experimental phenomena and can help to gain insights into the underlying pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Personalized, image‐based computational heart modelling is a powerful technology that can be used to improve patient‐specific arrhythmia risk stratification and ventricular tachycardia (VT) ablation targeting. However, most state‐of‐the‐art methods still require manual interactions by expert users. The goal of this study is to evaluate the feasibility of an automated, deep learning‐based workflow for reconstructing personalized computational electrophysiological heart models to guide patient‐specific treatment of VT. Contrast‐enhanced computed tomography (CE‐CT) images with expert ventricular myocardium segmentations were acquired from 111 patients across five cohorts from three different institutions. A deep convolutional neural network (CNN) for segmenting left ventricular myocardium from CE‐CT was developed, trained and evaluated. From both CNN‐based and expert segmentations in a subset of patients, personalized electrophysiological heart models were reconstructed and rapid pacing was used to induce VTs. CNN‐based and expert segmentations were more concordant in the middle myocardium than in the heart's base or apex. Wavefront propagation during pacing was similar between CNN‐based and original heart models. Between most sets of heart models, VT inducibility was the same, the number of induced VTs was strongly correlated, and VT circuits co‐localized. Our results demonstrate that personalized computational heart models reconstructed from deep learning‐based segmentations even with a small training set size can predict similar VT inducibility and circuit locations as those from expertly‐derived heart models. Hence, a user‐independent, automated framework for simulating arrhythmias in personalized heart models could feasibly be used in clinical settings to aid VT risk stratification and guide VT ablation therapy. Key points: Personalized electrophysiological heart modelling can aid in patient‐specific ventricular tachycardia (VT) risk stratification and VT ablation targeting.Current state‐of‐the‐art, image‐based heart models for VT prediction require expert‐dependent, manual interactions that may not be accessible across clinical settings.In this study, we develop an automated, deep learning‐based workflow for reconstructing personalized heart models capable of simulating arrhythmias and compare its predictions with that of expert‐generated heart models.The number and location of VTs was similar between heart models generated from the deep learning‐based workflow and expert‐generated heart models.These results demonstrate the feasibility of using an automated computational heart modelling workflow to aid in VT therapeutics and has implications for generalizing personalized computational heart technology to a broad range of clinical centres. [ABSTRACT FROM AUTHOR]

The KCNH family of potassium channels serves relevant physiological functions in both excitable and non-excitable cells, reflected in the massive consequences of mutations or pharmacological manipulation of their function. This group of channels shares structural homology with other voltage-gated K+ channels, but the mechanisms of gating in this family show significant differences with respect to the canonical electromechanical coupling in these molecules. In particular, the large intracellular domains of KCNH channels play a crucial role in gating that is still only partly understood. Using KCNH1(KV10.1) as a model, we have characterized the behavior of a series of modified channels that could not be explained by the current models. With electrophysiological and biochemical methods combined with mathematical modeling, we show that the uncovering of an open state can explain the behavior of the mutants. This open state, which is not detectable in wild-type channels, appears to lack the rapid flicker block of the conventional open state. Because it is accessed from deep closed states, it elucidates intermediate gating events well ahead of channel opening in the wild type. This allowed us to study gating steps prior to opening, which, for example, explain the mechanism of gating inhibition by Ca2+-Calmodulin and generate a model that describes the characteristic features of KCNH channels gating. [ABSTRACT FROM AUTHOR]