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Brain differences linked to autism spectrum disorder (ASD) can manifest before observable symptoms. Studying these early neural precursors in larger and more diverse cohorts is crucial for advancing our understanding of developmental pathways and potentially facilitating earlier identification. EEG is an ideal tool for investigating early neural differences in ASD, given its scalability and high tolerability in infant populations. In this context, we integrated EEG into an existing multi-site MRI study of infants with a higher familial likelihood of developing ASD. This paper describes the comprehensive protocol established to collect longitudinal, high-density EEG data from infants across five sites as part of the Infant Brain Imaging Study (IBIS) Network and reports interim feasibility and data quality results. We evaluated feasibility by measuring the percentage of infants from whom we successfully collected each EEG paradigm. The quality of task-free data was assessed based on the duration of EEG recordings remaining after artifact removal. Preliminary analyses revealed low data loss, with average in-session loss rates at 4.16 % and quality control loss rates at 11.66 %. Overall, the task-free data retention rate, accounting for both in-session issues and quality control, was 84.16 %, with high consistency across sites. The insights gained from this preliminary analysis highlight key sources of data attrition and provide practical considerations to guide similar research endeavors.

We present an unusual case of alternating left anterior and left posterior fascicular block. Given the known risk for progression to complete atrioventricular block with alternating right bundle and left bundle branch block, we performed an electrophysiological study. Findings were consistent with infra-Hisian disease, and the patient underwent pacemaker implantation.

MicroRNAs (miRs) are short, evolutionarily conserved noncoding RNAs that canonically downregulate expression of target genes. The miR family composed of miR-204 and miR-211 is among the most highly expressed miRs in the retinal pigment epithelium (RPE) in both mouse and human and also retains high sequence identity. To assess the role of this miR family in the developed mouse eye, we generated two floxed conditional KO mouse lines crossed to the RPE65-ERT2-Cre driver mouse line to perform an RPE-specific conditional KO of this miR family in adult mice. After Cre-mediated deletion, we observed retinal structural changes by optical coherence tomography; dysfunction and loss of photoreceptors by retinal imaging; and retinal inflammation marked by subretinal infiltration of immune cells by imaging and immunostaining. Single-cell RNA sequencing of diseased RPE and retinas showed potential miR-regulated target genes, as well as changes in noncoding RNAs in the RPE, rod photoreceptors, and Müller glia. This work thus highlights the role of miR-204 and miR-211 in maintaining RPE function and how the loss of miRs in the RPE exerts effects on the neural retina, leading to inflammation and retinal degeneration.

BACKGROUND: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. METHODS: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. DISCUSSION: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

Orphan solute carrier (SLC) represents a group of membrane transporters whose exact functions and substrate specificities are not known. Elucidating the function and regulation of orphan SLC transporters is not only crucial for advancing our knowledge of cellular and molecular biology but can potentially lead to the development of new therapeutic strategies. Here, we provide evidence for the biological function of a ubiquitous orphan lysosomal SLC, the Major Facilitator Superfamily Domain-containing Protein 1 (MFSD1), which has remained phylogenetically unassigned. Targeted metabolomics revealed that dipeptides containing either lysine or arginine residues accumulate in lysosomes of cells lacking MFSD1. Whole-cell patch-clamp electrophysiological recordings of HEK293-cells expressing MFSD1 on the cell surface displayed transport affinities for positively charged dipeptides in the lower mM range, while dipeptides that carry a negative net charge were not transported. This was also true for single amino acids and tripeptides, which MFSD1 failed to transport. Our results identify MFSD1 as a highly selective lysosomal lysine/arginine/histidine-containing dipeptide exporter, which functions as a uniporter.

The 1965 discovery of the P300 component of the electroencephalography (EEG)-based event-related potential (ERP), along with the subsequent identification of its alteration in people with schizophrenia, initiated over 50 years of P300 research in schizophrenia. Here, we review what we now know about P300 in schizophrenia after nearly six decades of research. We describe recent efforts to expand our understanding of P300 beyond its sensitivity to schizophrenia itself to its potential role as a biomarker of risk for psychosis or a heritable endophenotype that bridges genetic risk and psychosis phenomenology. We also highlight efforts to move beyond a syndrome-based approach to understand P300 within the context of the clinical, cognitive, and presumed pathophysiological heterogeneity among people diagnosed with schizophrenia. Finally, we describe several recent approaches that extend beyond measuring the traditional P300 ERP component in people with schizophrenia, including time-frequency analyses and pharmacological challenge studies, that may help to clarify specific cognitive mechanisms that are disrupted in schizophrenia. Moreover, we discuss several promising areas for future research, including studies of animal models that can be used for treatment development.

We present super-resolution microscopy of isolated functional mitochondria, enabling real-time studies of structure and function (voltages) in response to pharmacological manipulation. Changes in mitochondrial membrane potential as a function of time and position can be imaged in different metabolic states (not possible in whole cells), created by the addition of substrates and inhibitors of the electron transport chain, enabled by the isolation of vital mitochondria. By careful analysis of structure dyes and voltage dyes (lipophilic cations), we demonstrate that most of the fluorescent signal seen from voltage dyes is due to membrane bound dyes, and develop a model for the membrane potential dependence of the fluorescence contrast for the case of super-resolution imaging, and how it relates to membrane potential. This permits direct analysis of mitochondrial structure and function (voltage) of isolated, individual mitochondria as well as submitochondrial structures in the functional, intact state, a major advance in super-resolution studies of living organelles.

IntroductionIn primary auditory cortex (A1), nicotinic acetylcholine receptors (nAChRs) containing α2 subunits are expressed in layer 5 Martinotti cells (MCs)-inhibitory interneurons that send a main axon to superficial layers to inhibit distal apical dendrites of pyramidal cells (PCs). MCs also contact interneurons in supragranular layers that, in turn, inhibit PCs. Thus, MCs may regulate PCs via inhibition and disinhibition, respectively, of distal and proximal apical dendrites. Auditory inputs to PCs include thalamocortical inputs to middle layers relaying information about characteristic frequency (CF) and near-CF stimuli, and intracortical long-distance ("horizontal") projections to multiple layers carrying information about spectrally distant ("nonCF") stimuli. CF and nonCF inputs integrate to create broad frequency receptive fields (RFs). Systemic administration of nicotine activates nAChRs to "sharpen" RFs-to increase gain within a narrowed RF-resulting in enhanced responses to CF stimuli and reduced responses to nonCF stimuli. While nicotinic mechanisms to increase gain have been identified, the mechanism underlying RF narrowing is unknown.MethodsHere, we examine the role of α2 nAChRs in mice with α2 nAChR-expressing neurons labeled fluorescently, and in mice with α2 nAChRs genetically deleted.ResultsThe distribution of fluorescent neurons in auditory cortex was consistent with previous studies demonstrating α2 nAChRs in layer 5 MCs, including nonpyramidal somata in layer 5 and dense processes in layer 1. We also observed label in subcortical auditory regions, including processes, but no somata, in the medial geniculate body, and both fibers and somata in the inferior colliculus. Using electrophysiological (current-source density) recordings in α2 nAChR knock-out mice, we found that systemic nicotine failed to enhance CF-evoked inputs to layer 4, suggesting a role for subcortical α2 nAChRs, and failed to reduce nonCF-evoked responses, suggesting that α2 nAChRs regulate horizontal projections to produce RF narrowing.DiscussionThe results support the hypothesis that α2 nAChRs function to simultaneously enhance RF gain and narrow RF breadth in A1. Notably, a similar neural circuit may recur throughout cortex and hippocampus, suggesting widespread conserved functions regulated by α2 nAChRs.

The complexity of information processing in the brain requires the development of technologies that can provide spatial and temporal resolution by means of dense electrode arrays paired with high-channel-count signal acquisition electronics. In this work, we present an ultra-low noise modular 512-channel neural recording circuit that is scalable to up to 4096 simultaneously recording channels. The neural readout application-specific integrated circuit (ASIC) uses a dense 8.2 mm × 6.8 mm 2D layout to enable high-channel count, creating an ultra-light 350 mg flexible module. The module can be deployed on headstages for small animals like rodents and songbirds, and it can be integrated with a variety of electrode arrays. The chip was fabricated in a TSMC 0.18 µm 1.8 V CMOS technology and dissipates a total of 125 mW. Each DC-coupled channel features a gain and bandwidth programmable analog front-end along with 14 b analog-to-digital conversion at speeds up to 30 kS/s. Additionally, each front-end includes programmable electrode plating and electrode impedance measurement capability. We present both standalone and in vivo measurements results, demonstrating the readout of spikes and field potentials that are modulated by a sensory input.

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β and misfolded tau proteins causing synaptic dysfunction, and progressive neurodegeneration and cognitive decline. Altered neural oscillations have been consistently demonstrated in AD. However, the trajectories of abnormal neural oscillations in AD progression and their relationship to neurodegeneration and cognitive decline are unknown. Here, we deployed robust event-based sequencing models (EBMs) to investigate the trajectories of long-range and local neural synchrony across AD stages, estimated from resting-state magnetoencephalography. The increases in neural synchrony in the delta-theta band and the decreases in the alpha and beta bands showed progressive changes throughout the stages of the EBM. Decreases in alpha and beta band synchrony preceded both neurodegeneration and cognitive decline, indicating that frequency-specific neuronal synchrony abnormalities are early manifestations of AD pathophysiology. The long-range synchrony effects were greater than the local synchrony, indicating a greater sensitivity of connectivity metrics involving multiple regions of the brain. These results demonstrate the evolution of functional neuronal deficits along the sequence of AD progression.

Sleep is associated with many costs, but is also important to survival, with a lack of sleep impairing cognitive function and increasing mortality. Sleeping in groups could alleviate sleep‐associated costs, or could introduce new costs if social sleeping disrupts sleep. Working with the Jamaican fruit bat (Artibeus jamaicensis), we aimed to: (1) describe sleep architecture, (2) assess how sleeping in groups affects sleep, and (3) quantify total sleep time and identify rapid eye movement (REM) sleep using behavioral indicators that complement physiological evidence of sleep. Twenty‐five adult bats were captured in Panama and recorded sleeping in an artificial roost enclosure. Three bats were fitted with an electromyograph and accelerometer and video recorded sleeping alone in controlled laboratory settings. The remaining 22 bats were assigned to differing social configurations (alone, dyad, triad, and tetrad) and video recorded sleeping in an outdoor flight cage. We found that sleep was highly variable among individuals (ranging from 2 h 53 min to 9 h 39 min over a 12‐h period). Although we did not detect statistically significant effects and our sample size was limited, preliminary trends suggest that male bats may sleep longer than females, and individuals sleeping in groups may sleep longer than individuals sleeping alone. We also found a high correspondence between total sleep time quantified visually and quantified using actigraphy (with a 2‐min immobility threshold) and identified physiological correlates of behaviorally‐defined REM. These results serve as a starting point for future work on the ecology and evolution of sleep in bats and other wild mammals. [ABSTRACT FROM AUTHOR]

Several studies have implicated the L3 auditory interneuron in the regulation of syllable period selective phonotaxis in female cricket Acheta domesticus. The L3's response to model calls of conspecific males comprises of an immediate and a prolonged response. The kinetics of activation of these electrical activities are consistent with sequential activation of ionotropic and metabotropic mechanisms. In this study, we used electrophysiological and pharmacological tools to investigate the cellular mechanisms underlying L3's response. Bath application of the synthetic protein kinase inhibitor 1‐(5‐isoquinolinesul‐fonyl)‐2‐methylpiperazine (H7), results in the suppression of L3's spiking response, and this effect can be reversed by saline wash. Additionally, when female A. domesticus that were previously nano‐injected with H7 were tested for phonotaxis on a non‐compensating treadmill, they demonstrated suppression of syllable period‐dependent phonotaxis. These findings implicate protein kinase in the regulation of L3's spiking rhythm and the associated phonotaxis in A. domesticus. [ABSTRACT FROM AUTHOR]

Previous behavioral studies have shown that inter-letter spacing affects visual word recognition and reading. While condensed spacing may hinder the early stages of letter encoding because of increased crowding effects, the impact of expanded inter-letter spacing is still unclear. To examine the electrophysiological signature of inter-letter spacing on visual word recognition, we presented words in three different inter-letter spacing conditions (default, condensed [−1.5 points] or expanded [+1.5 points]) in an event-related potentials go/no-go semantic categorization task. Our focus was on the N170, an event-related potentials component associated with the early encoding of orthographic information, which also is sensitive to crowding effects. Results revealed that the N170 amplitude reached the largest values for the condensed condition than for the default and expanded spacing conditions, which did not differ. While increased crowding impacted the early encoding of orthographic information, extra letter spacing (compared with default spacing) did not. This outcome is consistent with the Modified Receptive Field hypothesis, in which letter receptors adapt their size to cope with letter crowding. These findings reveal that reducing the space between letters more than the default spacing impairs the ability to process written words, whereas slightly expanding the space between letters does not provide any additional benefit. [ABSTRACT FROM AUTHOR]

Neurofeedback techniques provide participants immediate feedback on neuronal signals, enabling them to modulate their brain activity. This technique holds promise to unveil brain–behavior relationship and offers opportunities for neuroenhancement. Establishing causal relationships between modulated brain activity and behavioral improvements requires rigorous experimental designs, including appropriate control groups and large samples. Our primary objective was to examine whether a single neurofeedback session, designed to enhance working memory through the modulation of theta or high-alpha frequencies, elicits specific changes in electrophysiological and cognitive outcomes. Additionally, we explored predictors of successful neuromodulation. A total of 101 healthy adults were assigned to groups trained to increase frontal theta, parietal high alpha, or random frequencies (active control group). We measured resting-state EEG, working memory performance, and self-reported psychological states before and after one neurofeedback session. Although our analyses revealed improvements in electrophysiological and behavioral outcomes, these gains were not specific to the experimental groups. An increase in the frequency targeted by the training has been observed for the theta and high alpha groups, but training designed to increase randomly selected frequencies appears to induce more generalized neuromodulation compared with targeting a specific frequency. Among all the predictors of neuromodulation examined, resting theta and high alpha amplitudes predicted specifically the increase of those frequencies during the training. These results highlight the challenge of integrating a control group based on enhancing randomly selected frequency bands and suggest potential avenues for optimizing interventions (e.g., by including a control group trained in both up- and down-regulation). [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Operative Orthopädie und Traumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Objectives Animals Methods Results Conclusions and Clinical Importance Myocardial sleeves of the caudal vena cava are the predilection site for atrial tachycardia (AT) in horses. Caudal vena cava isolation guided by the ablation index, a lesion quality marker incorporating power, duration and contact force, might improve outcome.Describe the feasibility and outcome of caudal vena cava isolation using ablation index‐guided radiofrequency catheter ablation (RFCA) to treat AT in horses.Ten horses with sustained AT.Records from 10 horses with sustained AT treated by three‐dimensional electro‐anatomical mapping and ablation index‐guided RFCA (CARTO™ 3) were reviewed.Three‐dimensional electro‐anatomical mapping of the right atrium identified a macro‐reentry circuit in the caudomedial right atrium (n = 10). Point‐by‐point RFCA was performed to isolate the myocardial sleeves of the caudal vena cava in power‐controlled mode with a mean of 17 ± 7 applications. The ablation index target was 400‐450. A median ablation index of 436 (range, 311‐763) was reached using a median maximum power of 35 (range, 24‐45) W for a median duration of 20 (range, 8‐45) seconds, with a median contact force of 10 (range, 3‐48) g. Sinus rhythm was restored in all 10 horses. To date, 9‐37 months post‐ablation, none of the horses have had recurrence.Caudal vena cava isolation using ablation index‐guided RFCA was feasible and effective to permanently treat sustained AT in horses. Ablation index guidance ensured efficient lesion creation, and isolation of the caudal vena cava eliminated the arrhythmogenic substrate, thereby minimizing the risk of recurrence. [ABSTRACT FROM AUTHOR]

It is widely acknowledged that microglia actively regulate synaptic function in the brain. Remarkably, much of our understanding regarding the role of microglia in synaptic regulation is derived from studies in acute brain slices. However, it is still uncertain to what extent the preparation and maintenance of acute slices can influence microglial function and whether microglial changes may affect synaptic transmission. In this study, we examined the impact of acute slice resting time on hippocampal CA1 microglia, by assessing morphological and functional parameters at two distinct time intervals. We report that after 4 h from slicing microglia undergo morphological, functional, and transcriptional changes, including a decrease in the number of branches and in their movement speed. Furthermore, microglia acquire a reactive phenotype, characterized by increased amplitude of outward rectifying K+ currents, increased expression of the pro-inflammatory cytokine Tnfα and altered expression of the microglial receptors Cx3cr1 and P2y12r. We also examined time-dependent changes of excitatory synaptic transmission in CA1 pyramidal neurons from acute hippocampal slices, reporting time-dependent decrease in both amplitude and frequency of postsynaptic currents (sEPSCs), along with a decrease in spine density. Noticeably, sEPSCs amplitude decrease was absent in slices prepared from PLX5622 microglia-depleted mice, suggesting that this time-dependent effect on synaptic transmission is microglia-dependent. Our findings highlight possible causal relation between microglia phenotypic changes in the hours following slice preparation and concomitant synaptic changes, pointing to the mechanisms of acute synaptic modulation, whose understanding is crucial for unraveling microglia-neurons interplay in nature. Furthermore, they emphasize the potential issues associated with experimental time windows in ex vivo samples. [ABSTRACT FROM AUTHOR]

Introduction: Coronary artery disease (CAD) is the foremost single cause of mortality and disability globally. Patients with type 2 diabetes (T2DM) have a higher incidence of CAD, and poorer prognosis. The low-grade inflammation associated to T2DM contributes to increased morbidity and worst outcomes after revascularization. Inflammatory signaling in the vasculature supports endothelial dysfunction, leukocyte infiltration, and macrophage activation to a metabolic disease (MMe) specific phenotype, which could contribute to the metabolic disorders and ascular damage in T2DM. We have previously found that Kv1.3 blockers inhibit the development of intimal hyperplasia, thereby preventing restenosis. This inhibition was enhanced in a mouse model of T2DM, where systemic Kv1.3 blockers administration also improve metabolic dysfunction by acting on unidentified cellular targets other than vascular smooth muscle. Here we characterize the MMe phenotype in our T2DM model with a focus on macrophage Kv1.3 channels, to explore their contribution to vascular disease and their potential role as targets to ameliorate T2DM vascular risk. Methods and Results: Male and female BPH mice fed on high-fat diet (HFD) develop metabolic syndrome (MetS) and T2DM. mRNA levels of several K+ channels (KV1.3, KCa3.1, Kir2.1) and macrophage markers (TNFα, NOS2, CD36) were analyzed. The MMe phenotype associated with increased CD36 expression. Channel-specific fingerprinting highlights a gender-specific increase of KV1.3 mRNA fold change in LPS stimulated macrophages from HFD compared to standard diet (SD). KV1.3 functional expression was also significantly increased after LPS stimulation in female HFD macrophages compared to SD. Functional studies showed that macrophage's KV1.3 channels of BPH female mice did not contribute to phagocytosis or metabolic profile but were relevant in cell migration rate. Conclusion: Altogether, our data suggest that by inhibiting macrophage infiltration, Kv1.3 blockers could contribute to disrupt the vicious cycle of inflammation and insulin resistance, offering a novel approach to prevent MetS, T2DM and its associated cardiovascular complications in females. [ABSTRACT FROM AUTHOR]

Key points Through the modulation of its surround, an identical visual stimulus can be perceived as more or less salient, allowing it to either stand out or seamlessly integrate with the rest of the visual scene. Gamma rhythms are associated with processing stimulus features across extensive areas of the visual field. Consistent with this concept, the magnitude of visually induced gamma rhythm depends on how well stimulus features aligned both within and outside the classical receptive field (CRF) at the recording site. However, there still exists some uncertainty regarding the encoding of context‐modulated orientation discontinuity by gamma rhythms. To address this concern, we conducted extracellular recordings in layers II/III and IV of area V1 using lightly anaesthetized mice to investigate the gamma tuning for stimuli with orientation discontinuity. Our study revealed that gamma rhythms exhibit a preference for stimuli with orientation discontinuity similar to the spiking responses observed in V1, which contradicts the findings of previous studies. Furthermore, the gamma tuning of discontinuous orientations exhibits a moderate correlation with spike tuning and a positive correlation with the strength of surround suppression. Therefore, our study suggests a close association between gamma tuning and nearby spiking tuning; additionally, it highlights the connection between the encoding of visual features by gamma rhythms and functional architecture, as well as neural signal integration. Visual context modulates the gamma rhythms in the primary visual cortex. Discontinuous orientation elicits significantly enhanced gamma rhythms compared to the iso‐orientation stimulus. The gamma tuning of discontinuous orientations exhibits a moderate correlation with spike tuning. Gamma tuning of orientation discontinuity exhibits a positive correlation with the strength of surround suppression. [ABSTRACT FROM AUTHOR]

Technologies for axon guidance for in vitro disease models and bottom up investigations are increasingly being used in neuroscience research. One of the most prevalent patterning methods is using polydimethylsiloxane (PDMS) microstructures due to compatibility with microscopy and electrophysiology which enables systematic tracking of axon development with precision and efficiency. Previous investigations of these guidance platforms have noted axons tend to follow edges and avoid sharp turns; however, the specific impact of spatial constraints remains only partially explored. We investigated the influence of microchannel width beyond a constriction point, as well as the number of available microchannels, on axon growth dynamics. Further, by manipulating the size of micron/submicron-sized PDMS tunnels we investigated the space restriction that prevents growth cone penetration showing that restrictions smaller than 350 nm were sufficient to exclude axons. This research offers insights into the interplay of spatial constraints, axon development, and neural behavior. The findings are important for designing in vitro platforms and in vivo neural interfaces for both fundamental neuroscience and translational applications in rapidly evolving neural implant technologies. [ABSTRACT FROM AUTHOR]

In this paper, we examine the time-dependent two-dimensional cable equation of fractional order in terms of the Caputo fractional derivative. This cable equation plays a vital role in diverse areas of electrophysiology and modeling neuronal dynamics. This paper conveys a precise semi-analytical method called the q-homotopy analysis transform method to solve the fractional cable equation. The proposed method is based on the conjunction of the q-homotopy analysis method and Laplace transform. We explained the uniqueness of the solution produced by the suggested method with the help of Banach's fixed-point theory. The results obtained through the considered method are in the form of a series solution, and they converge rapidly. The obtained outcomes were in good agreement with the exact solution and are discussed through the 3D plots and graphs that express the physical representation of the considered equation. It shows that the proposed technique used here is reliable, well-organized and effective in analyzing the considered non-homogeneous fractional differential equations arising in various branches of science and engineering. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions His‐bundle pacing (HBP) is a pacing mode that provides near‐physiological pacing and has more advantages over standard right ventricle (RV) septum pacing in positive clinical results. However, traditional HBP cannot accurately and stably place the lead tip into the His‐Purkinje system. Hence, this study aimed to establish a novel strategy for HBP to strike a balance between an excellent pacing threshold and minor injuries to the conduction system.HBP, using continuous and real‐time monitoring of unipolar His‐bundle (HB) electrograms along with electrocardiograms, was performed in 29 consecutive atrial fibrillation patients. We analyzed the unipolar HB intracardiac electrogram (EGM) and electrophysiological characteristics during HBP using John Jiang's connecting cable and an electrophysiology recording system. All patients were followed up for 12 months.Of the 29 patients, 28 (96.55%) successfully received HBP. Twenty‐one (75%) patients were confirmed to have the negative deflection of His potential with a negative amplitude of ≥ 0.1 mV in HB EGM. The subgroup with a deep negative deflection was recorded with an HBP threshold (0.71 ± 0.41 V), significantly lower than those thresholds with no deep negative deflection (1.83 ± 0.76 V) (p < 0.05). The selective HBP rate was significantly different between the two groups: 20 (95.24%) in the deep negative deflection group and three (42.86%) in the non‐deep negative deflection group (p < 0.05); five (17.24%) patients presented right bundle branch block (RBBB) during the lead placement.This study supports the safety and feasibility of using an uninterrupted real‐time monitoring technique for HBP. An uninterrupted real‐time monitoring technique can guide the accurate placement of the HB lead and may provide a balance between an excellent pacing threshold and minor injury to the conduction system. [ABSTRACT FROM AUTHOR]

The case was a 15‐year‐old male with a history of paroxysmal supraventricular tachycardia refractory to medical therapy and prior catheter. A repeat electrophysiology study and catheter ablation were applied. Baseline AH and HV intervals were 100 and 55 ms during normal sinus rhythm (NSR), respectively. Programmed atrial stimulation induced a short RP narrow complex tachycardia (HV interval 22 ms) with an incomplete right bundle branch block configuration and right axis deviation. Tachycardia was terminated with ATP 5 mg injection. An atrial premature beat within the His refractory period advanced and reset tachycardia. Entrainment performed from the coronary sinus and left ventricle both showed a post‐pacing interval minus tachycardia cycle length (TCL) of 90 ms. After confirming the diagnosis, left atrial mapping along mitral annulus was performed using trans‐septal access and accessory pathway potentials were recorded during NSR and tachycardia at the superior mitral annulus. An irrigated ablation catheter guided by 3‐D mapping was used to perform ablation during tachycardia. Tachycardia terminated immediately during the first RF application with ensuing automaticity exhibiting a warm‐up during radiofrequency delivery and a cooling down upon the suspension of ablation. Therefore, all phenomena of Mahaim‐fiber associated tachycardia were observed. In this case, we describe an antidromic atrio‐ventricular reentry tachycardia using a left atrio‐fascicular fiber inserting into the proximal left anterior fascicle. [ABSTRACT FROM AUTHOR]

Background: Transseptal puncture (TSP) is a critical step in electrophysiological (EP) procedures, as a misdirected TSP can result in life-threatening complications. Although TSP is predominantly performed under fluoroscopic guidance in EP procedures, transesophageal echocardiography (TEE) offers more precision and certainty in the localization of the transseptal needle at the interatrial septum. Despite the widespread use of TSP, evidence supporting the added value of TEE-guided TSP in EP procedures remains limited. This study evaluates the impact of additional TEE guidance on TSP-associated complications during EP procedures. Methods: This study enrolled patients who underwent left atrial or left ventricular procedures with TSP, performed either without (fluoroscopy group) or with additional TEE guidance (TEE group), at the University Heart Center Ulm, Germany. Results: A total of 932 patients were included: 443 in the TEE group (mean age 68.1 ± 11.8 years, 40.6% female) and 489 in the fluoroscopy group (mean age 68.8 ± 11.0 years, 38.2% female). The mean number of transseptal accesses per patient was 1.18 ± 0.38 in the TEE group and 1.14 ± 0.34 in the fluoroscopy group (p = 0.101). Pericardial tamponade occurred significantly less in the TEE group (0.5%) than in the fluoroscopy group (1.8%; p = 0.046). Logistic regression revealed a 91.8% lower risk of pericardial tamponade with TEE-guided TSP compared to fluoroscopy guidance alone. The overall TEE complication rate was low (0.9%). Conclusions: TEE guidance during TSP significantly reduces the risk of pericardial tamponade in EP procedures, indicating that TSP should be performed with additional sonographic guidance to increase patient safety. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study is to document outcomes of ablation for high-risk accessory pathways in paediatrics using 3D mapping systems with minimal to zero fluoroscopy. Methods: It is a cross-sectional, multicentre study, conducted between 2013 and 2023, and involving four different centres in Hungary, Croatia, Kuwait, and Slovenia. Results: A total of 128 procedures were performed on 111 patients. The cohort included 57.8% anteroseptal (AS) pathways and 42.2% midseptal (MS) pathways. The mean follow-up time was 2.0 ± 2.1 years. Cryoablation was used in 72.7% of the cases, and radiofrequency ablation was used in 27.3%. The EnSite Precision™ Cardiac Mapping System was the predominant system used. The overall acute success rate was 89.1%, with recurrence rates at 17.2% with similar results regardless of the type of energy used. The success rate was not significantly different between AS and MS substrates. The age and weight of the patient had no bearing on the outcomes (median age and weight were 13 years and 52 kg, respectively). The complications rate was at 4.69% and included transient AV block (three patients), hematoma (one patient), right bundle branch block (one patient), and possible permanent complete AV block (one patient). Fluoroscopy was utilized in 18 cases, with a fluoroscopy time mean of 3 min and 45 s. Conclusions: MS and AS AP in paediatric patients can be treated effectively with either RF or cryoablation and with a low dose of radiation using 3D mapping systems, with excellent acute success rates and low complication rates. [ABSTRACT FROM AUTHOR]

Simultaneously recording network activity and ultrastructural changes of the synapse is essential for advancing understanding of the basis of neuronal functions. However, the rapid millisecond‐scale fluctuations in neuronal activity and the subtle sub‐diffraction resolution changes of synaptic morphology pose significant challenges to this endeavor. Here, specially designed graphene microelectrode arrays (G‐MEAs) are used, which are compatible with high spatial resolution imaging across various scales as well as permit high temporal resolution electrophysiological recordings to address these challenges. Furthermore, alongside G‐MEAs, an easy‐to‐implement machine learning algorithm is developed to efficiently process the large datasets collected from MEA recordings. It is demonstrated that the combined use of G‐MEAs, machine learning (ML) spike analysis, and 4D structured illumination microscopy (SIM) enables monitoring the impact of disease progression on hippocampal neurons which are treated with an intracellular cholesterol transport inhibitor mimicking Niemann–Pick disease type C (NPC), and show that synaptic boutons, compared to untreated controls, significantly increase in size, leading to a loss in neuronal signaling capacity. [ABSTRACT FROM AUTHOR]

A key feature of the receptive field of neurons in the visual system is their centre–surround antagonism, whereby the centre and the surround exhibit responses of opposite polarity. This organization is thought to enhance visual acuity, but whether and how such antagonism plays a role in more complex processing remains poorly understood. Here, we investigate the role of centre and surround receptive fields in retinal direction selectivity by exposing posterior‐preferring On–Off direction‐selective ganglion cells (pDSGCs) to adaptive light and recording their response to globally moving objects. We reveal that light adaptation leads to surround expansion in pDSGCs. The pDSGCs maintain their original directional tuning in the centre receptive field, but present the oppositely tuned response in their surround. Notably, although inhibition is the main substrate for retinal direction selectivity, we found that following light adaptation, both the centre‐ and surround‐mediated responses originate from directionally tuned excitatory inputs. Multi‐electrode array recordings show similar oppositely tuned responses in other DSGC subtypes. Together, these data attribute a new role for excitation in the direction‐selective circuit. This excitation carries an antagonistic centre–surround property, possibly designed to sharpen the detection of motion direction in the retina. Key points: Receptive fields of direction‐selective retinal ganglion cells expand asymmetrically following light adaptation.The increase in the surround receptive field generates a delayed spiking phase that is tuned to the null direction and is mediated by excitation.Following light adaptation, excitation rules the computation in the centre receptive field and is tuned to the preferred direction.GABAergic and glycinergic inputs modulate the null‐tuned delayed response differentially.Null‐tuned delayed spiking phases can be detected in all types of direction‐selective retinal ganglion cells.Light adaptation exposes a hidden directional excitation in the circuit, which is tuned to opposite directions in the centre and surround receptive fields. [ABSTRACT FROM AUTHOR]

Heart failure (HF) patients suffer from cognitive decline and mood impairments, but the molecular signals and brain circuits underlying these effects remain elusive. The hypothalamic neuropeptide oxytocin (OT) is critically involved in regulating mood, and OTergic signalling in the central amygdala (CeA) is a key mechanism that controls emotional responses including anxiety‐like behaviours. Still, whether an altered OTergic signalling contributes to mood disorders in HF remains unknown. To address this, we used an ischaemic rat HF model, along with a highly multidisciplinary approach, to mechanistically study multiple levels of the hypothalamus‐to‐CeA OTergic circuit in male rats with HF. We aimed to test the hypothesis that sustained activation of the OT system following an infarct leads to depletion of OT content in this pathway, with subsequent changes in OT receptor expression and blunted modulation of local GABAergic circuits. We found that most of OTergic innervation of the CeA originated from the supraoptic nucleus (SON). While no differences in the numbers of SON→CeA OTergic neurons was observed between sham and HF rats, we observed a blunted content and release of OT from axonal terminals within the CeA. Moreover, we report downregulation of neuronal and astrocytic OT receptors, and impaired OTR‐driven GABAergic synaptic activity within the CeA microcircuit of HF rats. We provide the first evidence that male HF rats display perturbations in the hypothalamus‐to‐amygdala OTergic circuit, laying the foundation for future translational studies targeting either the OT system or GABAergic amygdalar microcircuit to ameliorate mood impairments in rats or patients with chronic HF. Key points: Heart failure patients suffer from cognitive decline, depression and mood impairments, but the underlying mechanisms remain elusive.Acting within the central amygdala, the neuropeptide oxytocin regulates emotional responses, including anxiety‐like behaviours. However, whether changes in oxytocin signalling occurs during heart failure is unknown.In this study, we used an ischaemic rat heart failure model to mechanistically study multiple levels of the hypothalamus‐to‐amygdala oxytocinergic circuit in this disease.We report an overall blunted oxytocinergic signalling pathway in rats with heart failure, including blunted content and release of oxytocin from axonal terminals, downregulation of neuronal and astrocytic oxytocin receptors, and impaired oxytocin‐driven GABAergic synaptic activity within the central amygdala microcircuit of HF rats.These studies shed light on mechanisms that contribute to mood disorders in cardiovascular disease states and help to identify potential molecular targets for their improved treatment. [ABSTRACT FROM AUTHOR]

To investigate the difference in preoperative retinal function in patients with type 2 diabetes cataract (DC) without obvious retinopathy and to explore the clinical application of full blood glucose management for improving the postoperative vision in DC patients. This was a retrospective analysis in which we estimated the changes in visual electrophysiology (N75, P100, photopic flash electroretinogram(FERG), and scotopic FERG, paraoptic retinal nerve fibre layer thickness (pRNFL) and paraoptic radial capillary network blood flow density (ppVD) of type 2 diabetes (T2DM) patients at different phases of disease progression along with fasting blood glucose (FBG) and glycosylated haemoglobin (HbAlC) levels before and after DC surgery at Ziyang Central Hospital from January 2020 to December 2022. Additionally, trends in the above data throughout the entire process of glucose management intervention were examined. As the course of T2DM progressed, FBG and HbA1c increased, the N75 and P100 latency periods of patients gradually increased, and the values of photopic FERG, scotopic FERG, pRNFL, and ppVD gradually decreased at each postoperative time point. Moreover, the best corrected visual acuity(BCVA) of patients after surgery gradually decreased (P < 0.05). The BCVA of Group B (with full process blood glucose management) gradually stabilized at 1 month after surgery, and the BCVA of Group B was better than that of Group A at all time points after surgery. The results revealed that N75 and P100 in Group A were greater than those in Group B, whereas the photopic and scotopic FERG, pRNFL, and ppVD (%) values in Group A were lower than those in Group B. In addition, N75 and P100 in Group A gradually increased at various time points after surgery, whereas the photopic FERG, scotopic FERG, pRNFL, and ppVD (%) values gradually decreased. In the state of full blood glucose management, although N75 and P100 both reached their longest durations at one week after surgery, N75, the P100, photopic FERG, scotopic FERG, and pRNFL showed a gradually decreasing trend at 1 month and 3 months after surgery, whereas ppVD (%) gradually increased (P < 0.05). According to the results of the quantitative analysis of visual electrophysiology and OCTA, with the aggravation of diabetes, the retinal function of DC patients without obvious retinopathy tends to decrease, but full-process blood glucose management can effectively recover the retinal function of DC patients and improve visual quality after surgery. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications Patients suffering from ischaemic heart disease and heart failure are at high risk of recurrent ventricular arrhythmias (VAs), eventually leading to sudden cardiac death. While high‐voltage shocks delivered by an implantable defibrillator may prevent sudden cardiac death, these interventions themselves impair quality of life and raise both morbidity and mortality, which accentuates the need for developing novel defibrillation techniques.Photopharmacology allows for reversible control of biological processes by light. When relying on synthetic and externally applied chromophores, it renders genetic modification of target cells dispensable and may hence be advantageous over optogenetic approaches. Here, the photochromic ligand azobupivacaine 2 (AB2) was probed as a modulator of cardiac electrophysiology in an ex vivo intact mouse heart model.By reversibly blocking voltage‐gated Na+ and K+ channels, photoswitching of AB2 modulated both the ventricular effective refractory period and the conduction velocity in native heart tissue. Moreover, photoswitching of AB2 was able to convert VA into sinus rhythm.The present study provides the first proof of concept that AB2 enables gradual control of cardiac electrophysiology by light. AB2 may hence open the door to the development of an optical defibrillator based on photopharmacology. [ABSTRACT FROM AUTHOR]

The author comments on calculating a corrected QT interval (QTc) in acute care settings and the significant role of pharmacists in QTc interpretation. Topics discussed include standards for pharmacists in assessing the risk of QTc prolongation, the methods used to correct QT values, and factors to be considered in assessing the risk of torsades de pointes.

The visual system needs to identify perceptually relevant borders to segment complex natural scenes. The primary visual cortex (V1) is thought to extract local borders, and higher visual areas are thought to identify the perceptually relevant borders between objects and the background. To test this conjecture, we used natural images that had been annotated by human observers who marked the perceptually relevant borders. We assessed the effect of perceptual relevance on V1 responses using human neuroimaging, macaque electrophysiology, and computational modeling. We report that perceptually relevant borders elicit stronger responses in the early visual cortex than irrelevant ones, even if simple features, such as contrast and the energy of oriented filters, are matched. Moreover, V1 neurons discriminate perceptually relevant borders surprisingly fast, during the early feedforward-driven activity at a latency of ~50 ms, indicating that they are tuned to the features that characterize them. We also revealed a delayed, contextual effect that enhances the V1 responses that are elicited by perceptually relevant borders at a longer latency. Our results reveal multiple mechanisms that allow V1 neurons to infer the layout of objects in natural images. [ABSTRACT FROM AUTHOR]

Basolateral amygdala (BLA) neurons are engaged by emotionally salient stimuli. An area of increasing interest is how BLA dynamics relate to evolving reward-seeking behavior, especially under situations of uncertainty or ambiguity. Here, we recorded the activity of individual BLA neurons in male rats across the acquisition and extinction of conditioned reward seeking. We assessed ongoing neural dynamics in a task where long reward cue presentations preceded an unpredictable, variably time reward delivery. We found that, with training, BLA neurons discriminated the CS+ and CS- cues with sustained cue-evoked activity that correlated with behavior and terminated only after reward receipt. BLA neurons were bidirectionally modulated, with a majority showing prolonged inhibition during cued reward seeking. Strikingly, population-level analyses revealed that neurons showing cue-evoked inhibitions and those showing excitations similarly represented the CS+ and behavioral state. This sustained population code rapidly extinguished in parallel with conditioned behavior. We next assessed the contribution of the orbitofrontal cortex (OFC), amajor reciprocal partner to the BLA. Inactivation of the OFC while simultaneously recording in the BLA revealed a blunting of sustained cue-evoked activity in the BLA that accompanied reduced reward seeking. Optogenetic disruption of BLA activity and OFC terminals in the BLA also reduced reward seeking. Our data indicate that the BLA represents reward-seeking states via sustained, bidirectional cue-driven neural encoding. This code is regulated by cortical input and is important for the maintenance of vigilant reward-seeking behavior. [ABSTRACT FROM AUTHOR]

How consciousness is lost in states such as sleep or anesthesia remains a mystery. To gain insight into this phenomenon, concurrent recordings of electrophysiology signals in the anterior cingulate cortex and whole‐brain functional magnetic resonance imaging (fMRI) are conducted in rats exposed to graded propofol, undergoing the transition from consciousness to unconsciousness. The results reveal that upon the loss of consciousness (LOC), there is a sharp increase in low‐frequency power of the electrophysiological signal. Additionally, fMRI signals exhibit a cascade of deactivation across a pathway including the hippocampus, thalamus, and medial prefrontal cortex (mPFC) surrounding the moment of LOC, followed by a broader increase in brain activity across the cortex during sustained unconsciousness. Furthermore, sliding window analysis demonstrates a temporary increase in synchrony of fMRI signals across the hippocampus‐thalamus‐mPFC pathway preceding LOC. These data suggest that LOC may be triggered by sequential activities in the hippocampus, thalamus, and mPFC, while wide‐spread activity increases in other cortical regions commonly observed during anesthesia‐induced unconsciousness may be a consequence, rather than a cause of LOC. Taken together, the study identifies a cascade of neural events unfolding as the brain transitions into unconsciousness, offering insight into the systems‐level neural mechanisms underpinning LOC. [ABSTRACT FROM AUTHOR]

Background: Patients with migraine often experience not only headache pain but also cognitive dysfunction, particularly in attention, which is frequently overlooked in both diagnosis and treatment. The influence of these attentional deficits on the pain-related clinical characteristics of migraine remains poorly understood, and clarifying this relationship could improve care strategies. Methods: This study included 52 patients with migraine and 34 healthy controls. We employed the Attentional Network Test for Interactions and Vigilance–Executive and Arousal Components paradigm, combined with electroencephalography, to assess attentional deficits in patients with migraine, with an emphasis on phasic alerting, orienting, executive control, executive vigilance, and arousal vigilance. An extreme gradient boosting binary classifier was trained on features showing group differences to distinguish patients with migraine from healthy controls. Moreover, an extreme gradient boosting regression model was developed to predict clinical characteristics of patients with migraine using their attentional deficit features. Results: For general performance, patients with migraine presented a larger inverse efficiency score, a higher prestimulus beta-band power spectral density and a lower gamma-band event-related synchronization at Cz electrode, and stronger high alpha-band activity at the primary visual cortex, compared to healthy controls. Although no behavior differences in three basic attentional networks were found, patients showed magnified N1 amplitude and prolonged latency of P2 for phasic alerting-trials as well as an increased orienting evoked-P1 amplitude. For vigilance function, improvements in the hit rate of executive vigilance-trials were exhibited in controls but not in patients. Besides, patients with migraine exhibited longer reaction time as well as larger variability in arousal vigilance-trials than controls. The binary classifier developed by such attentional deficit features achieved an F1 score of 0.762 and an accuracy of 0.779 in distinguishing patients with migraine from healthy controls. Crucially, the predicted value available from the regression model involving attentional deficit features significantly correlated with the real value for the frequency of headache. Conclusions: Patients with migraine demonstrated significant attentional deficits, which can be used to differentiate migraine patients from healthy populations and to predict clinical characteristics. These findings highlight the need to address cognitive dysfunction, particularly attentional deficits, in the clinical management of migraine. [ABSTRACT FROM AUTHOR]

[Display omitted] • N400 and P600 ERPs evoked in adolescents ignoring sentences with semantic errors. • Semantic processing is fundamentally different in passive versus active contexts. • We provide 22 control adolescent high-density electrophysiological BIDs datasets. Language comprehension requires semantic processing of individual words and their context within a sentence. Well-characterized event-related potential (ERP) components (the N400 and late positivity component (LPC/P600)) provide neuromarkers of semantic processing, and are robustly evoked when semantic errors are introduced into sentences. These measures are useful for evaluating semantic processing in clinical populations, but it is not known whether they can be evoked in more severe neurodevelopmental disorders where explicit attention to the sentence inputs cannot be objectively assessed (i.e., when sentences are passively listened to). We evaluated whether N400 and LPC/P600 could be detected in adolescents who were explicitly ignoring sentence inputs. Specifically, it was asked whether explicit attention to spoken inputs was required for semantic processing, or if a degree of automatic processing occurs when the focus of attention is directed elsewhere? High-density ERPs were acquired from twenty-two adolescents (12–17 years), under two experimental conditions: 1. individuals actively determined whether the final word in a sentence was congruent or incongruent with sentence context, or 2. passively listened to background sentences while watching a video. When sentences were ignored, N400 and LPC/P600 were robustly evoked to semantic errors, albeit with reduced amplitudes and protracted/delayed latencies. Statistically distinct topographic distributions during passive versus active paradigms pointed to distinct generator configurations for semantic processing as a function of attention. Covert semantic processing continues in neurotypical adolescents when explicit attention is withdrawn from sentence inputs. As such, this approach could be used to objectively investigate semantic processing in populations with communication deficits. [ABSTRACT FROM AUTHOR]

Resting-state functional magnetic resonance imaging (RS-fMRI) has been extensively utilized for noninvasive investigation of human brain activity. While studies employing simultaneous recordings of fMRI and electrophysiology have established a connection between the low-frequency fluctuation (< 0.1 Hz) observed in RS-fMRI and the local field potential (LFP), it remains unclear whether the RS-fMRI signal exhibits frequency-dependent modulation, which is a well-documented phenomenon in LFP. The present study concurrently recorded resting-state functional magnetic resonance imaging (RS-fMRI) and local field potentials (LFP) in the striatum of 8 rats before and after a pharmacological manipulation. We observed a highly similar frequency-dependent pattern of amplitude changes in both RS-fMRI and LFP following the manipulation, specifically an increase in high-frequency band amplitudes accompanied by a decrease in low-frequency band amplitudes. These findings provide direct evidence that the enhanced high-frequency fluctuations and reduced low-frequency fluctuations observed in RS-fMRI may reflect heightened neuronal activity. [ABSTRACT FROM AUTHOR]

Background: Bell's palsy significantly impacts facial function, aesthetics, and quality of life. Objective: To compare the effects of the Kabat Technique (KT) and Mirror Book Therapy (MBT) on clinical and electrophysiological parameters in patients with Bell's palsy. Methods: This randomized controlled trial included 31 patients divided into two groups: KT (n = 16) and MBT (n = 15). Both groups received their respective interventions (6 days/week for 3 weeks) in addition to conventional physiotherapy. Sunnybrook Facial Grading Score and Nerve Conduction Test (amplitude and latency of frontalis, nasalis, and mentalis muscles) were assessed pre- and post-intervention. Results: Statistical analysis (SPSS v20) revealed significant intragroup improvements in all outcome measures (p < 0.05). Intergroup comparison showed MBT had superior improvements in amplitude of frontalis and reduced latency of nasalis. Both groups demonstrated significant improvement in the Sunnybrook grade shift. Conclusion: This study suggests that KT and MBT, combined with conventional physiotherapy, positively impact clinical and electrophysiological parameters in Bell's Palsy patients. MBT showed superior results in select Nerve Conduction Test parameters. [ABSTRACT FROM AUTHOR]

Background: Cochlear synaptopathy is a disorder where auditory perceptual impairments, such as speech perception in noise and tinnitus, may not be accurately reflected by audiometric thresholds, even if the audiogram appears normal. It is proposed that the connections between hair cells and the auditory nerve are more susceptible to sound and aging damage than the cochlea's hair cells. Cochlear synaptopathy can be present in ears with normal audiograms and undamaged hair cells, leading to hidden hearing loss. This study aims to construct electrophysiological and behavioral auditory parameters associated with persons exposed to loudness and having normal audiograms and auditory complaints to identify hidden hearing loss. Results: A case–control study was done with forty participants with a documented history of exposure to loud sounds and various auditory complaints, compared to a control group of forty persons who had all been confirmed to have normal audiograms. The chosen behavioral core tests comprised the speech intelligibility in noise test (SPIN), gaps detection in noise (GIN test), and pitch pattern sequence test (PPS). The electrophysiological measures utilized in the study were the auditory brainstem response test (ABR) and electrocochleography (ECochG). The SPIN, PPS, and GIN test results demonstrated statistically significant disparities between the control and case groups. The amplitude ratio of wave I to wave V in ABR and the ratio of EcochG AP to SP demonstrated a statistically significant variance between the two groups. The SPIN test exhibited the highest AUC, signifying its superior diagnostic capability in identifying hidden hearing loss. Conclusion: The present study has shown that the SPIN, as a behavioral test, and the EcochG AP amplitude measure, as an electrophysiological test, provide the greatest auditory diagnostic capability for identifying cochlear synaptopathy. Wave I amplitude in the auditory brainstem response (ABR) and the SP/AP ratio in electrocochleography (EcochG) are promising non-behavioral measures of cochlear synaptopathy or hidden hearing loss. [ABSTRACT FROM AUTHOR]

Children with neurodevelopmental disorders, such as developmental coordination disorder (DCD), exhibit gross to fine sensorimotor impairments, reduced physical activity and interactions with the environment and people. This disorder co‐exists with cognitive deficits, executive dysfunctions and learning impairments. Previously, we demonstrated in rats that limited amounts and atypical patterns of movements and somatosensory feedback during early movement restriction manifested in adulthood as degraded postural and locomotor abilities, and musculoskeletal histopathology, including muscle atrophy, hyperexcitability within sensorimotor circuitry and maladaptive cortical plasticity, leading to functional disorganization of the primary somatosensory and motor cortices in the absence of cortical histopathology. In this study, we asked how this developmental sensorimotor restriction (SMR) started to impact the integration of multisensory information and the emergence of sensorimotor reflexes in rats. We also questioned the enduring impact of SMR on motor activities, pain and memory. SMR led to deficits in the emergence of swimming and sensorimotor reflexes, the development of pain and altered locomotor patterns and posture with toe‐walking, adult motor performance and night spontaneous activity. In addition, SMR induced exploratory hyperactivity, short‐term impairments in object‐recognition tasks and long‐term deficits in object‐location tasks. SMR rats displayed minor alterations in histological features of the hippocampus, entorhinal, perirhinal and postrhinal cortices yet no obvious changes in the prefrontal cortex. Taken all together, these results show similarities with the symptoms observed in children with DCD, although further exploration seems required to postulate whether developmental SMR corresponds to a rat model of DCD. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Understanding the neural mechanisms underlying migraine and other primary headache disorders is critical for the development of long‐term cures. Magnetoencephalography (MEG), an imaging modality that measures neuronal currents and cortical excitability with high temporal and superior spatial resolution, has been increasingly used in neurological research. Initial MEG studies showed promise in directly recording cortical spreading depression—a cortical correlate of migraine with aura. However, lately MEG technology has highly evolved with greater potential to reveal underlying pathophysiology of migraine and primary headache disorders, and aid in the identification of biomarkers.To systematically review the use of MEG in migraine and other primary headache disorders and summarize findings.We conducted a systematic search and selection of MEG studies in migraine and primary headache disorders from inception until June 8, 2023, in Medline, Embase, Cochrane, and Scopus databases. Peer‐reviewed English articles reporting the use of MEG for clinical or research purposes in migraine and primary headache disorders were selected.We found 560 articles and included 38 in this review after screening. Twelve studies investigated resting‐state, while others investigated a sensory modality using an evoked or event‐related paradigm with a total of 35 cohort and 3 case studies. Thirty‐two studies focused exclusively on migraine, while the rest reported other primary headache disorders.The findings show an evolution of MEG from a 7‐ to a 306‐channel system and analysis evolving from sensor‐level evoked responses to more advanced source‐level connectivity measures. A relatively few MEG studies portrayed migraine and primary headache disorders as a sensory abnormality, especially of the visual system. We found heterogeneity in the datasets, data reporting standards (due to constantly evolving MEG technology and analysis methods), and patient characteristics. Studies were inadequately powered and there was no evidence of blinding procedures to avoid selection bias in case–control studies, which could have led to false‐positive findings. More studies are needed to investigate the affective–cognitive aspects that exacerbate pain and disability in migraine and primary headache disorders. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications Mutations in both KCNQ1 and KCNE1, which together form the cardiac IKs current, are associated with inherited conditions such as long and short QT syndromes. Mefenamic acid, a non‐steroidal anti‐inflammatory drug, is an IKs potentiator and may be utilised as an archetype to design therapeutically useful IKs agonists. However, here we show that mefenamic acid can also act as an IKs inhibitor, and our data reveal its dual effects on KCNQ1/KCNE1 channels.Effects of mefenamic acid on wild type (WT) and mutant KCNQ1/KCNE1 channels expressed in tsA201 cells were studied using whole cell patch clamp. Molecular dynamics simulations were used to determine trajectory clustering.Mefenamic acid inhibits WT IKs at high concentrations while preserving some attributes of current potentiation. Inhibitory actions of mefenamic acid are unmasked at lower drug concentrations by KCNE1 and KCNQ1 mutations in the mefenamic acid binding pocket, at the extracellular end of KCNE1 and in the KCNQ1 S6 helix. Mefenamic acid does not inhibit KCNQ1 in the absence of KCNE1 but inhibits IKs current in a concentration‐dependent manner in the mutant channels. Inhibition involves modulation of pore kinetics and/or voltage sensor domain‐pore coupling in WT and in the KCNE1 E43C mutant.This work highlights the importance of structural motifs at the extracellular inter‐subunit interface of KCNQ1 and KCNE1 channels, and their interactions, in determining the nature of drug effects on the IKs channel complex and has important implications for treating patients with specific long QT mutations. [ABSTRACT FROM AUTHOR]

Key event-related potentials (ERPs) of perceptual decision-making such as centroparietal positivity (CPP) elucidate how evidence is accumulated toward a given choice. Furthermore, this accumulation can be impacted by visual target selection signals such as the N2 contralateral (N2c). How these underlying neural mechanisms of perceptual decision-making are influenced by the spatial congruence of distractors relative to target stimuli remains unclear. Here, we used electroencephalography (EEG) in humans of both sexes to investigate the effect of distractor spatial congruency (same vs different hemifield relative to targets) on perceptual decision-making.We confirmed that responses for perceptual decisions were slower for spatially incongruent versus congruent distractors of high salience. Similarly, markers of target selection (N2c peak amplitude) and evidence accumulation (CPP slope) were found to be lower when distractors were spatially incongruent versus congruent. To evaluate the effects of congruency further, we applied drift diffusion modeling to participant responses, which showed that larger amplitudes of both ERPs were correlated with shorter nondecision times when considering the effect of congruency. The modeling also suggested that congruency's effect on behavior occurred prior to and during evidence accumulation when considering the effects of the N2c peak and CPP slope. These findings point to spatially incongruent distractors, relative to congruent distractors, influencing decisions as early as the initial sensory processing phase and then continuing to exert an effect as evidence is accumulated throughout the decision-making process. Overall, our findings highlight how key electrophysiological signals of perceptual decision-making are influenced by the spatial congruence of target and distractor. [ABSTRACT FROM AUTHOR]

Transient receptor potential canonical (TRPC)5 channel is a non-selective cation channel that plays a significant role in membrane depolarization and calcium influx. TRPC5 not only forms homotetramers itself but also heterotetramers with TRPC1. However, accurately testing and confirming these heterotetrameric channels at specific ratios has proven challenging. Therefore, creating heteromeric concatemers of TRPC5 and TRPC1 with a fixed stoichiometry of 1:1 becomes essential. This study aims to meticulously identify and reaffirm the properties of TRPC5 homomers and heteromers with a 1:1 fixed stoichiometry to determine the optimal ratio for the TRPC1/5 heterotetramer. The overall characteristics were consistent with those of the previous studies, but several specific features were different. The TRPC1–TRPC5 concatemer is activated by Englerin A and GiQL, whereas carbachol alone does not trigger its activation. Additionally, GqQL significantly inhibited the current when co-expressed with the concatemer. Interestingly, carbachol can activate the TRPC1–TRPC5 concatemer in the presence of internal GTPγS, highlighting the influence of intracellular signaling conditions on its activation. Meanwhile, the TRPC5–TRPC5 concatemer is responsive to both carbachol and Englerin A. In conclusion, we provide evidence that the TRPC1–TRPC5 heteromeric concatemer with fixed stoichiometry need specific conditions to respond to carbachol, whereas the TRPC5–TRPC5 homomeric concatemer responds physiologically to carbachol. Additional research may be necessary to ascertain the optimal stoichiometry for the TRPC1–TRPC5 concatemer to enhance its electrophysiological properties. [ABSTRACT FROM AUTHOR]

Acquiring and exploiting memories of rewarding experiences is critical for survival. The spatial environment in which a rewarding stimulus is encountered regulates memory retrieval. The ventral hippocampus (vH) has been implicated in contextual memories involving rewarding stimuli such as food, social cues or drugs. Yet, the neuronal representations and circuits underlying contextual memories of socially rewarding stimuli are poorly understood. Here, using in vivo electrophysiological recordings, in vivo one-photon calcium imaging, and optogenetics during a social reward contextual conditioning paradigm in male mice, we show that vH neurons discriminate between contexts with neutral or acquired social reward value. The formation of context-discriminating vH neurons following learning was contingent upon the presence of unconditioned stimuli. Moreover, vH neurons showed distinct contextual representations during the retrieval of social reward compared to fear contextual memories. Finally, optogenetic inhibition of locus coeruleus (LC) projections in the vH selectively disrupted social reward contextual memory by impairing vH contextual representations. Collectively, our findings reveal that the vH integrates contextual and social reward information, with memory encoding of these representations supported by input from the LC. The neuronal mechanisms serving contextual memories of socially rewarding stimuli are unclear. Here the authors demonstrate that neurons in the ventral hippocampus of male mice discriminate between neutral and socially rewarding contexts, a process dependent on input from the locus coeruleus. [ABSTRACT FROM AUTHOR]

Background: The demand for fresh strategies to analyze intricate multidimensional data in neuroscience is increasingly evident. One of the most complex events during our neurodevelopment is adolescence, where our nervous system suffers constant changes, not only in neuroanatomical traits but also in neurophysiological components. One of the most impactful factors we deal with during this time is our environment, especially when encountering external factors such as social behaviors or substance consumption. Binge drinking (BD) has emerged as an extended pattern of alcohol consumption in teenagers, not only affecting their future lifestyle but also changing their neurodevelopment. Recent studies have changed their scope into finding predisposition factors that may lead adolescents into this kind of patterns of consumption. Methods: In this article, using unsupervised machine learning (UML) algorithms, we analyze the relationship between electrophysiological activity of healthy teenagers and the levels of consumption they had 2 years later. We used hierarchical agglomerative UML techniques based on Ward's minimum variance criterion to clusterize relations between power spectrum and functional connectivity and alcohol consumption, based on similarity in their correlations, in frequency bands from theta to gamma. Results: We found that all frequency bands studied had a pattern of clusterization based on anatomical regions of interest related to neurodevelopment and cognitive and behavioral aspects of addiction, highlighting the dorsolateral and medial prefrontal, the sensorimotor, the medial posterior, and the occipital cortices. All these patterns, of great cohesion and coherence, showed an abnormal electrophysiological activity, representing a dysregulation in the development of core resting‐state networks. The clusters found maintained not only plausibility in nature but also robustness, making this a great example of the usage of UML in the analysis of electrophysiological activity—a new perspective into analysis that, while contributing to classical statistics, can clarify new characteristics of the variables of interest. [ABSTRACT FROM AUTHOR]

Canine distemper (CD) is a deadly, multi-system infection caused by a Morbillivirus. The canine distemper virus (CDV) frequently affects the nervous system with demyelinating leukoencephalitis, the most common neurological lesion. The disease has been linked to multiple sclerosis (MS) in humans due to similar clinical presentation and pathophysiological mechanisms. In MS, visual evoked potentials (VEPs) have been identified as a reliable marker for disease progression, enabling the early detection of clinically suspected lesions. The aim of this study was to determine if there are any abnormalities in VEP responses in dogs with neurological CD. Visual evoked potentials and electroretinogram (ERG) were recorded at both the cranial and spinal levels in dogs naturally infected with CDV and in healthy dogs. The results in the CDV-infected group revealed a bilateral increase in the latency of N1, P1, N2, P2, and N3 waves of the VEPs, without any alterations in their amplitudes. No significant differences were observed in the ERG between the groups. These results suggest that altered VEP responses could serve as an early diagnostic indicator of neurological damage caused by distemper. Therefore, conducting these studies could potentially aid in the detection of central nervous conduction disorders during the subclinical phases of the disease. [ABSTRACT FROM AUTHOR]