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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.

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.

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]

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.

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]

Key points 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. 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]

[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]

Introduction: In 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. Methods: Here, we examine the role of α2 nAChRs in mice with α2 nAChR-expressing neurons labeled fluorescently, and in mice with α2 nAChRs genetically deleted. Results: The 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. Discussion: The 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. [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]

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]

Neurostimulation protocols are increasingly used as therapeutic interventions, including for brain injury. In addition to the direct activation of neurons, these stimulation protocols are also likely to have downstream effects on those neurons' synaptic outputs. It is well known that alterations in the strength of synaptic connections (long-term potentiation, LTP; long-term depression, LTD) are sensitive to the frequency of stimulation used for induction; however, little is known about the contribution of the temporal pattern of stimulation to the downstream synaptic plasticity that may be induced by neurostimulation in the injured brain. We explored interactions of the temporal pattern and frequency of neurostimulation in the normal cerebral cortex and after mild traumatic brain injury (mTBI), to inform therapies to strengthen or weaken neural circuits in injured brains, as well as to better understand the role of these factors in normal brain plasticity. Whole-cell (WC) patch-clamp recordings of evoked postsynaptic potentials in individual neurons, as well as field potential (FP) recordings, were made from layer 2/3 of visual cortex in response to stimulation of layer 4, in acute slices from control (naive), sham operated, and mTBI rats. We compared synaptic plasticity induced by different stimulation protocols, each consisting of a specific frequency (1 Hz, 10 Hz, or 100 Hz), continuity (continuous or discontinuous), and temporal pattern (perfectly regular, slightly irregular, or highly irregular). At the individual neuron level, dramatic differences in plasticity outcome occurred when the highly irregular stimulation protocol was used at 1 Hz or 10 Hz, producing an overall LTD in controls and shams, but a robust overall LTP after mTBI. Consistent with the individual neuron results, the plasticity outcomes for simultaneous FP recordings were similar, indicative of our results generalizing to a larger scale synaptic network than can be sampled by individual WC recordings alone. In addition to the differences in plasticity outcome between control (naive or sham) and injured brains, the dynamics of the changes in synaptic responses that developed during stimulation were predictive of the final plasticity outcome. Our results demonstrate that the temporal pattern of stimulation plays a role in the polarity and magnitude of synaptic plasticity induced in the cerebral cortex while highlighting differences between normal and injured brain responses. Moreover, these results may be useful for optimization of neurostimulation therapies to treat mTBI and other brain disorders, in addition to providing new insights into downstream plasticity signaling mechanisms in the normal brain. [ABSTRACT FROM AUTHOR]

When exposed to X-rays, scintillators emit visible luminescence. X-ray-mediated optogenetics employs scintillators for remotely activating light-sensitive proteins in biological tissue through X-ray irradiation. This approach offers advantages over traditional optogenetics, allowing for deeper tissue penetration and wireless control. Here, we assessed the short-term safety and efficacy of candidate scintillator materials for neuronal control. Our analyses revealed that lead-free halide scintillators, such as Cs3Cu2I5, exhibited significant cytotoxicity within 24 h and induced neuroinflammatory effects when injected into the mouse brain. In contrast, cerium-doped gadolinium aluminum gallium garnet (Ce:GAGG) nanoparticles showed no detectable cytotoxicity within the same period, and injection into the mouse brain did not lead to observable neuroinflammation over four weeks. Electrophysiological recordings in the cerebral cortex of awake mice showed that X-ray-induced radioluminescence from Ce:GAGG nanoparticles reliably activated 45% of the neuronal population surrounding the implanted particles, a significantly higher activation rate than europium-doped GAGG (Eu:GAGG) microparticles, which activated only 10% of neurons. Furthermore, we established the cell-type specificity of this technique by using Ce:GAGG nanoparticles to selectively stimulate midbrain dopamine neurons. This technique was applied to freely behaving mice, allowing for wireless modulation of place preference behavior mediated by midbrain dopamine neurons. These findings highlight the unique suitability of Ce:GAGG nanoparticles for X-ray-mediated optogenetics. The deep tissue penetration, short-term safety, wireless neuronal control, and cell-type specificity of this system offer exciting possibilities for diverse neuroscience applications and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a neuronal protein important in maintaining axonal integrity and motor function and may be important in the pathogenesis of many neurological disorders. UCHL1 may ameliorate acute injury and improve recovery after cerebral ischemia. In the current study, the hypothesis that UCHL1's hydrolase activity underlies its effect in maintaining axonal integrity and function is tested after ischemic injury. Hydrolase activity was inhibited by treatment with a UCHL1 hydrolase inhibitor or by employing knockin mice bearing a mutation in the hydrolase active site (C90A). Ischemic injury was induced by oxygen-glucose deprivation (OGD) in brain slice preparations and by transient middle cerebral artery occlusion (tMCAO) surgery in mice. Hydrolase activity inhibition increased restoration time and decreased the amplitude of evoked axonal responses in the corpus callosum after OGD. Mutation of the hydrolase active site exacerbated white matter injury as detected by SMI32 immunohistochemistry, and motor deficits as detected by beam balance and cylinder testing after tMCAO. These results demonstrate that UCHL1 hydrolase activity ameliorates white matter injury and functional deficits after acute ischemic injury and support the hypothesis that UCHL1 activity plays a significant role in preserving white matter integrity and recovery of function after cerebral ischemia. [ABSTRACT FROM AUTHOR]

Background Although the four-class system of classifying premature ejaculation (PE), including lifelong PE (LPE), acquired PE (APE), natural variable PE (NPE), and subjective PE (SPE), has existed for many years, objective classification standards in clinical practice are lacking. Aim In this study, we sought to investigate the use of electrophysiologic parameters to assist in the classification of PE, thereby guiding subsequent treatment. Methods From July 2023 to April 2024, 187 study participants were enrolled. For each participant, the biological sensory threshold (BST), penile sympathetic skin response (PSSR), and dorsal nerve somatosensory evoked potential (DNSEP) were recorded. Outcomes The differences in the PSSR latencies (PL) and DNSEP latencies (DL), the PSSR amplitudes (PA) and DNSEP amplitudes (DA), and the BST were compared among the LPE, APE, SPE, NPE, and healthy control (HC) groups. Results The participants were divided into the LPE (46 cases), APE (53 cases), SPE (20 cases), NPE (33 cases), and HC (35 cases) groups. The results showed shorter latencies of the PSSR (PL) and DNSEP (DL), larger amplitudes of the PSSR (PA) and DNSEP (DL), and smaller BST in the LPE group than in the NPE, SPE, APE, and HC groups (P  < .05). In addition, the larger PA and shorter PL in the APE group than in the NPE and HC groups (P  < .05). However, the electrophysiological parameters were not significantly different among the NPE, SPE, and HC groups (P  > .05). In addition, PL <1262.0 milliseconds and DL <41.85 milliseconds were strong predictors of LPE, 1262.0 milliseconds < PL <1430.0 milliseconds was a predictor of APE, and PL >1430.0 milliseconds suggested possible SPE or NPE. Clinical implications Analysis of the electrophysiological parameters of PE may be helpful for classification and treatment. Strengths and Limitations No previous study, to our knowledge, has analyzed the electrophysiological parameters of the four types of PE. The main limitation is the small sample size. Conclusion APE is characterized by increased sympathetic excitability, whereas LPE is characterized by increased penile sensitivity and increased sympathetic excitability. However, penile sensitivity and sympathetic excitability in SPE and NPE patients may not differ significantly from normal. [ABSTRACT FROM AUTHOR]

Electrophysiological and behavioural correlates of true and false memories were examined in the Deese/Roediger-McDermont (DRM) paradigm. A mass univariate approach for analysing event-related potentials (ERP) in the temporal domain was used to examine the electrophysiological effects associated with this paradigm precisely (point-by-point) and without bias (data-driven). Behaviourally, true and false recognition did not differ, and the predicted DRM effect was observed, as false recognition of critical lures (i.e., new words semantically related to studied words) was higher than false alarms of new (unrelated) words. Neurally, an expected old/new effect was observed during the time-range of the late positive component (LPC) over left centro-parietal scalp electrodes. Furthermore, true recognition also evoked larger LPC amplitudes than false recognition over both left centro-parietal and fronto-central scalp electrodes. However, we did not observe LPC-related differences between critical lures and new words, nor between correct rejections of critical lures and new words. In contrast, correct rejections of critical lures were accompanied by higher activation of a sustained positive slow wave (SPSW) in right fronto-central electrodes beyond 1200 ms. This result reveals a key role of post-retrieval processes in recognition. Results are discussed in light of theoretical approaches to false memory in the DRM paradigm. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is highly prevalent in the Australian community, ranking amongst the highest globally. The consequences of AF are significant. Stroke, dementia and heart failure risk are increased substantially, hospitalisations are amongst the highest for all cardiovascular causes, and Australians living with AF suffer from substantial symptoms that impact quality of life. Australian research has made a significant impact at the global level in advancing the care of patients living with AF. However, new strategies are required to reduce the growing incidence of AF and its associated healthcare demand. The Australian Cardiovascular Alliance (ACvA) has led the development of an arrhythmia clinical theme with the objective of tackling major research priorities to achieve a reduction in AF burden across Australia. In this summary, we highlight these research priorities with particular focus on the strengths of Australian research and the strategies needed to move forward in reducing incident AF and improving outcomes for those who live with this chronic condition. [ABSTRACT FROM AUTHOR]

Introduction: Left atrial appendage occlusion (LAAO) can be performed using diverse anesthetic approaches ranging from moderate sedation (MS) to general anesthesia (GA), and guided by intracardiac echocardiography (ICE) or transesophageal echocardiography (TEE). Prior studies have demonstrated shorter time in lab for heart rhythm procedures performed under MS. The objective of this study was to compare laboratory times, acute procedural outcomes and complication rates for LAAO procedures performed using MS and 4‐dimensional ICE as opposed to GA. Methods and Results: This was a retrospective observational cohort study of 135 consecutive patients who were referred for LAAO to be performed with either GA or MS between June 2022 and April 2024. The primary endpoints were total laboratory time, procedure time, nonprocedure time, and fluoroscopy time. The secondary endpoints were stroke, peri‐device leak (>5 mm), device‐related left atrial thrombus, cardiovascular mortality, and all‐cause mortality at 45 days and 6 months postprocedure, where data were available. The mean age of patients in the study was 78.8 ± 7.8 years and 64.4% were male with no difference between GA and MS. In the MS group, 4D‐ICE was used for intraprocedural imaging in 95.5% of patients and 2 dimensional‐ICE (2D‐ICE) was used in 4.5% of patients. In the GA group, intra‐procedural imaging was done using TEE in 51.5%, 2D‐ICE in 32.4% and 4D‐ICE in 16.2% of cases. Total laboratory time was significantly lower in the MS group compared to the GA group (68.3 ± 23.1 vs 117.1 ± 34.3 min; p < 0.001), due to shorter nonprocedure time (15.2 ± 9.1 vs 63.7 ± 22.0 min; p < 0.001), with no significant difference in procedure time and fluoroscopy time. There was no significant difference in complications at 45 days and 6 months postprocedure. Conclusion: In this single center study, MS reduced total lab time by reducing nonprocedure time when compared to GA for LAAO, without affecting clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Typical atrial flutter (AFL) is a macroreentrant tachycardia in which intracardiac conduction rotates counterclockwise around the tricuspid annulus. Typical AFL has specific electrocardiographic characteristics, including a negative sawtooth‐like wave in the inferior lead and a positive F wave in lead V1. This study aimed to analyze the origin of the positive F wave in lead V1, which has not been completely understood. Methods: This study enrolled 10 patients who underwent radiofrequency catheter ablation for a typical AFL. Electroanatomical mapping was performed both during typical AFL and entrainment from the right atrial appendage (RAA). The 12‐lead electrocardiogram (ECG) and three‐dimensional (3D) electroanatomical maps were analyzed. Results: The positive F wave in lead V1 changed during entrainment from the RAA in all the cases. The 3D map during entrainment from the RAA revealed an area of antidromic capture around the RAA, which collided with the orthodromic wave in the anterior right atrium. This area of antidromic capture around the RAA was the only difference from the 3D electroanatomical map of AFL and is considered the cause of the change in the F wave in lead V1 during entrainment. Conclusion: The analysis of the differences in the 12‐lead ECG and 3D maps between tachycardia and entrainment from the RAA clearly demonstrated that activation around the RAA is responsible for the generation of the positive F wave in lead V1 of typical AFL. [ABSTRACT FROM AUTHOR]

Introduction: Understanding the spatiotemporal location of the spontaneous termination of ventricular tachycardia (VT) may provide new insights for ablation. To test the hypothesis that spontaneous VT termination most frequently occurs at the VT exit due to source‐sink mismatch and to characterize electrophysiological properties of the sites termination during VT and with extra‐stimulus technique. Methods: Retrospective analysis of intraoperative mapping studies of nine patients with ischemic cardiopathy or repaired tetralogy of Fallot. Simultaneous endocardial and epicardial mapping was performed in both ventricles using a custom mapping array during VT. Electrogram (EGM) characteristics before and at the moment of termination were analyzed including: cycle length oscillations, EGM heterogeneity and a variation in the systolic/diastolic path. The decrements to extra stimulus were analysed for termination sites and other diastolic sites. Results: Nine VTs in seven patients demonstrated spontaneous VT termination. Seven VTs (77.8%) spontaneously terminated in the final third of the systolic interval, one (11.1%) in early diastole and one (11.1%) in mid diastole. Cycle length oscillations (prolongation, shortening, and no change) were seen in equal frequency. Four VTs (44.4%) showed alternans in the local EGM at the site of termination and this was more prevalent than alternans at other sites in the diastolic pathway (p <.001). Only one‐third of VTs showed a change in activation pattern before termination. There was no difference based on etiology. During substrate characterization with extra‐stimulus pacing, sites of spontaneous termination showed greater decrement than other sites of the VT circuit during pacing (43.5 ± 14.5 ms vs. 31.2 ± 31.2 ms; p =.003). Conclusion: The entrance zone rather than the exit is the commonest site for the spontaneous termination of VT in the human heart. These sites tend to demonstrate EGM alternans during VT and greater decrement during extrastimulus pacing. These findings may help guide future studies into improving the success of VT ablation. [ABSTRACT FROM AUTHOR]

Background and aims: Methods for femoral venous haemostasis following electrophysiology (EP) procedures include manual compression (MC) and suture‐based techniques such as a figure‐of‐eight suture secured with a hand‐tied knot (Fo8HT) or a modified figure‐of‐eight suture secured with a 3‐way stopcock (Fo8MOD). We hypothesised that short‐term bleeding outcomes using the Fo8MOD approach would be superior to MC. We additionally compared outcomes between Fo8MOD and Fo8HT approaches. Methods: We studied consecutive patients undergoing EP procedures at our institution between March and December 2023. Patients were categorised into three haemostasis groups: MC, Fo8HT and Fo8MOD. Access site complications were classified as major (requiring intervention or blood transfusion, delaying discharge or resulting in death) or minor (bleeding/haematoma requiring additional compression). Results: 1089 patients were included: MC 718 (65.9%); Fo8HT 105 (9.6%); Fo8MOD 266 (24.4%). Procedures were most commonly for atrial fibrillation (52.4%), atrial flutter (10.9%), and atrioventricular nodal re‐entrant tachycardia (10.1%). In patients receiving periprocedural anticoagulation (865, 79.4%), Fo8MOD associated with fewer complications than MC or Fo8HT (major: MC 2.2%, Fo8HT 6.0%, Fo8MOD 0.8%, p =.01; minor: MC 16.5%, Fo8HT 12.0%, Fo8MOD 7.4%, p =.002). In patients not receiving periprocedural anticoagulation, complications did not differ between haemostasis methods (total major and minor complications 5.8%, p =.729 for between groups rates). On multivariable logistic regression, Fo8MOD was associated with a significantly lower risk of access site complications (OR 0.29 [95% CI 0.17–0.48], p <.001), whilst intraprocedural heparinisation (OR 5.25 [2.88–9.69], p <.001) and larger maximal sheath size (OR 1.06 [1.00–1.11], p =.04) were associated with a higher risk of complications. Conclusion: Femoral haemostasis with Fo8MOD associates with fewer access site complications than MC and Fo8HT following EP procedures that need periprocedural anticoagulation. [ABSTRACT FROM AUTHOR]

Introduction: The reduction of fluoroscopic exposure during catheter ablation of supraventricular arrhythmias is widely adopted by experienced electrophysiology physicians with a relatively short learning curve and is becoming the standard of care in many parts of the world. While observational studies in the United States and some parts of Western Europe have evaluated the minimal fluoroscopic approach, there are scarce real‐world data for this technique and the generalizability of outcomes in other economic regions. Method: The AALARA study is a prospective, observational, multicenter, and multinational open‐label study. Patients were recruited from 13 countries across Central Eastern Europe, North and South Africa, the Middle East, and the CIS (Commonwealth of Independent States), with different levels of operator expertise using minimal fluoroscopic exposure techniques. Data on radiation exposure, procedural success, complications, recurrence, and quality of life changes were collected and analyzed. Result: A total of 680 patients were enrolled and followed for 6 months. The majority were ablation naïve with the commonest arrhythmia ablated being typical AVNRT (58%) followed by Atrial Flutter (23%). Zero fluoroscopy exposure was observed in almost 90% of the cases. Fluoroscopy was most commonly used during the ablation phase of the procedure. We observed a high acute success rate (99%), a low complication rate (0.4%), and a 6‐month recurrence rate of 3.8%. There was a significant improvement in the patient's symptoms and quality of life as measured by patient global assessment. Conclusion: The routine use of a 3D mapping system during right‐sided ablation was associated with low radiation exposure and associated with high acute success rate, low complications, and recurrence rate along with significant improvement in quality of life. The data confirm the reproducibility of this approach in real‐world settings across different healthcare systems, and operator experience supporting this approach to minimize radiation exposure without compromising efficacy and safety. Trial Registration: NCT04716270 [ABSTRACT FROM AUTHOR]

Background: Low voltage areas (LVA) are pivotal in atrial fibrillation (AF) pathogenesis, influencing local left atrial LA excitation and perpetuating AF occurrences. While pulmonary vein isolation (PVI) with cryo‐balloon (CB) ablation is effective for AF, it doesn't provide insights into the LA substrate or detect LVA, which affects ablation success rates. This study examines whether LA voltage and LVAs can be anticipated by analyzing the voltage signal amplitude at the coronary sinus (CS) catheter, which is standard in CB and radiofrequency ablation procedures. Methods: A retrospective analysis of 284 patients with recurrent AF undergoing RF catheter ablation was conducted at a high‐volume EP center in Germany. The correlation between LA voltage and LVA with the CS signal was explored. Results: The signal amplitude in the CS significantly correlated with voltage in LA walls, particularly in the proximal CS (correlation coefficient ρ = 0.81, p < 0.001). A CS signal cut‐off of 1.155 mV effectively predicted severe atrial LVAs (>40%) with a sensitivity of 90.7% and a specificity of 100%. While a threshold of 1.945 mV identified patients with no significant atrial LVAs (<5%) with a sensitivity of 88% and a specificity of 50% (AUC: 0.81, 95% CI: 0.71–0.89, p < 0.001). Conclusion: The CS signal amplitude is associated with the LA voltage. Due to its potential as a diagnostic tool for atrial LVAs, the signal amplitude in the CS could provide valuable information about the LA substrate, especially when 3D mapping is not feasible. [ABSTRACT FROM AUTHOR]

Catheter ablation for tachyarrhythmia via superior approach has been used in patients without possible inferior vena cava access such as in cases of venous occlusion or complex anomaly. Difficulty in catheter manipulation, instability, number of required vascular access, and radiation exposure of operator had been described in the procedure. Application of three‐dimensional (3‐D) mapping system in catheter ablation via superior approach could navigate the guiding catheter and provide more precise ablation. We reported four cases receiving catheter ablation due to atrioventricular nodal reentry tachycardia, atrial fibrillation, and right ventricular arrhythmia via superior approach facilitated by 3‐D mapping system with fewer vascular access and catheters. [ABSTRACT FROM AUTHOR]

We report a case of a 44‐year‐old male who underwent an electrophysiological study for symptomatic supraventricular tachycardia (SVT) with wide QRS complex. The SVT was diagnosed as an antidromic atrioventricular reentrant tachycardia (AVRT) via antegrade conduction of left‐sided accessory pathway (AP). However, the QRS morphology changed during the SVT, and then the SVT was terminated spontaneously. The mapping of AP was performed during sinus rhythm, and the radiofrequency application successfully eliminated the AP, which rendered tachycardias non‐inducible. This was a rare case of antidromic AVRT during which the QRS morphology changed. [ABSTRACT FROM AUTHOR]

Research into the function of deep brain structures has benefited greatly from microelectrode recordings in animals. This has helped to unravel physiological processes in the healthy and malfunctioning brain. Translation to the human is necessary for improving basic understanding of subcortical structures and their implications in diseases. The use of microelectrode recordings as a standard component of deep brain stimulation surgery offers the most viable route for studying the electrophysiology of single cells and local neuronal populations in important deep structures of the human brain. Most of the studies in the basal ganglia have targeted the motor loop and movement disorder pathophysiology. In recent years, however, research has diversified to include limbic and cognitive processes. This review aims to provide an overview of advances in neuroscience made using intraoperative and post‐operative recordings with a focus on non‐motor activity in the basal ganglia. [ABSTRACT FROM AUTHOR]

Gilles de la Tourette syndrome (GTS) and dystonia (DYS) are both hyperkinetic movement disorders effectively treated by deep brain stimulation (DBS) of the internal part of the globus pallidus (GPi). In this study, we compared single‐neuron activity in the GPi between 18 GTS patients (with an average of 41 cells per patient) and 17 DYS patients (with an average of 54 cells per patient), all of whom underwent bilateral pallidal stimulation surgery, under general anesthesia or while awake at rest. We found no significant differences in GPi neuronal activity characteristics between patients operated on under general anesthesia versus those who were awake, irrespective of their diagnosis (GTS or DYS). We found higher firing rates, firing rate in bursts, pause duration and interspike interval coefficient of variation in GTS patients compared to DYS patients. On the opposite, we found higher number of pauses and bursts frequency in DYS patients. Lastly, we found a higher proportion of GPi oscillatory activities in DYS compared to GTS patients, with predominant activity within the low‐frequency band (theta/alpha) in both patient groups. These findings underscore the complex relationship between the different neuronal discharge characteristic such as oscillatory or bursting activity within the GPi in shaping the clinical phenotypes of hyperkinetic disorders. Further research is warranted to deepen our understanding of how neuronal patterns are transmitted within deep brain structures and to develop strategies aimed at normalizing these pathological activities, by refining DBS techniques to enhance treatment efficacy and individual outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this study were to characterize the electrodiagnostic findings of radial neuropathy using motor segmental conduction study and to determine the utility of subsequent inching test in precise lesion localization. Design: Twenty-three patients with radial neuropathy were evaluated using radial neuropathy using motor segmental conduction study with three-point stimulation. The pathomechanism of the lesions according to the radial neuropathy using motor segmental conduction study was classified into three groups: conduction block, mixed lesion (combination of conduction block and axonal degeneration), and axonal degeneration. Inching test was performed in patients with conduction block to localize the lesion site, and needle electromyography identified the most proximal radial nerve-innervated muscles affected. Results: Out of 23 cases, the radial neuropathy using motor segmental conduction study demonstrated probable partial conduction block in 10, mixed lesions in 2, and axonal degeneration in 10. One case could not be categorized with radial neuropathy using motor segmental conduction study alone. As determined by radial neuropathy using motor segmental conduction study and inching test, the most common cause of conduction block was compression, while the most common cause of axonal degeneration was iatrogenic. In the conduction block group, the lesion locations identified by radial neuropathy using motor segmental conduction study and inching test were consistent with needle electromyography localization. Conclusions: The combined radial neuropathy using motor segmental conduction study and inching test technique can precisely localize radial motor nerve injuries and provide detailed information on electrodiagnostic characteristics of radial mononeuropathy [ABSTRACT FROM AUTHOR]

Remembering when events occur in time is fundamental to episodic memory. Yet, many experiences repeat over time creating the potential for interference when attempting to recall temporally specific memories. Here, we argue that temporal memories are protected, in part, by reinstatement of temporal context information that is triggered by stimulus repetitions. We motivate this argument by integrating seminal findings across several distinct literatures and methodologies. Specifically, we consider key insights from foundational behavioral studies of temporal memory, recent electrophysiological and neuroimaging approaches to measuring memory reinstatement, and computational models that describe how temporal context representations shape memory processes. We also note several open questions concerning how temporal context reinstatement might influence subsequent temporal memory, including potential mediating effects of event spacing and event boundaries. These ideas and questions have the potential to guide future research and, ultimately, to advance theoretical accounts of how we preserve temporal memories. [ABSTRACT FROM AUTHOR]

Prior research on task switching has shown that the reconfiguration of stimulus–response mappings across trials is associated with behavioral switch costs. Here, we investigated the effects of switching representations of target‐defining features in visual search (attentional templates). Participants searched for one of two color‐defined target objects that changed predictably every two trials (Experiment 1) or every four trials (Experiment 2). Substantial costs were observed for search performance on target switch relative to target repeat trials. Preparatory target template activation processes were tracked by measuring N2pc components (indicative of attentional capture) to a rapid series of task‐irrelevant color singleton probes that appeared during the interval between search displays, and either matched the currently relevant or the other target color. N2pcs to relevant target color probes emerged from 800 ms before search display onset on target repetition trials, reflecting the activation of a corresponding color template. Crucially, probe N2pcs only emerged immediately before target onset on target switch trials, indicating that preparatory template activation was strongly delayed. In contrast, irrelevant color singleton probes did not trigger N2pcs on either repeat or switch trials, suggesting the absence of any target template inertia across trials. These results show that switching the identity of search targets delays preparatory target template activation and impairs subsequent attentional guidance processes. They suggest that performance costs on switch versus repeat trials are associated with differences in the time course of task preparation. Switching between cognitive tasks results in substantial performance costs, but the mechanisms responsible for these costs are not yet fully understood. Using electrophysiological markers of task preparation processes in visual search, we show that preparation is delayed when the identity of an upcoming search target changes. This new finding suggests strong links between switch costs and the time course of activating preparatory attentional task sets. [ABSTRACT FROM AUTHOR]

Our actions shape our everyday experience: what we experience, how we perceive, and remember it are deeply affected by how we interact with the world. Performing an action to deliver a stimulus engages neurophysiological processes which are reflected in the modulation of sensory and pupil responses. We hypothesized that these processes shape memory encoding, parsing the experience by grouping self‐ and externally generated stimuli into differentiated events. Participants encoded sound sequences, in which either the first or last few sounds were self‐generated and the rest externally generated. We tested recall of the sequential order of sounds that had originated from the same (within event) or different sources (across events). Memory performance was not higher for within‐event sounds, suggesting that actions did not structure the memory representation. However, during encoding, we observed the expected electrophysiological response attenuation for self‐generated sounds, together with increased pupil dilation triggered by actions. Moreover, at the boundary between events, physiological responses to the first sound from the new source were influenced by the direction of the source switch. Our results suggest that introducing actions creates a stronger contextual shift than removing them, even though actions do not directly contribute to memory performance. This study contributes to our understanding of how interacting with sensory input shapes experiences by exploring the relationships between action effects on sensory responses, pupil dilation, and memory encoding. Importantly, it challenges the notion of a meaningful contribution from low‐level neurophysiological mechanisms associated with action execution in the modulation of the self‐generation effect. The way we remember events is heavily influenced by how we acted when experiencing them, but the possible contribution of low‐level physiological mechanisms in this phenomenon has been so far overlooked. We show that the presence or absence of actions acts as a meaningful context for sound encoding. Low‐level neuromodulatory mechanisms are engaged during overt actions, and sensory processing is dramatically affected. However, these neurophysiological processes appear to have no impact on auditory memory. We conclude that the mere presence or absence of overt actions during sound sequence encoding, and the neurophysiological processes engaged by them, does not meaningfully contribute to structure auditory memory representations. [ABSTRACT FROM AUTHOR]

Objective: Distracted driving is a primary contributor to for motor vehicle crashes, the leading cause for injuries and fatalities for youth. Although attention and working memory clearly underlie driving abilities, few studies explore these functions on the brain-level under the cognitive load of driving. To understand the load driving has on auditory attention processing, we examined the differences in dynamic brain response to auditory stimuli during LOAD (while driving in a high-fidelity driving simulator) and No-LOAD conditions (seated in simulator, parked on the side of the road). Methods: Twenty-seven young adult drivers (18–27 y/o; 15 = women) completed a Selective Auditory Attention Task during both a LOAD (driving) and No-LOAD condition in a ½ cab miniSim® high-fidelity driving simulator. During the task, participants responded by pressing the volume control button on the steering wheel when a target tone was presented to a target ear. Electroencephalography-recorded event-related brain responses to the target tones were evaluated through alpha and theta oscillations for two response windows (early: 150–330ms; late: 350–540ms). Results: During an early time window, we observed a significant interaction between attended/unattended and LOAD/No-LOAD theta power in the right frontal cortical region (F(1, 24)= 5.4, p=.03, partial η2=.18). During the later window, we observed a significant interaction between attended/unattended and LOAD/No-LOAD alpha response in the posterior cortical region (F(1, 24)=11.81, p=.002, partial η2=.15) and in the right temporal cortical region during the window (F(1, 24)=4.3, p=.05, partial η2=.33). Conclusions: Our data provide insight into the demand that driving has on cognitive faculties and how dual task engagement may draw resources away from driving. We suggest future research directly incorporate vehicle control abilities into study design to understand how brain-based measures relate to driving behaviors. [ABSTRACT FROM AUTHOR]

The stability of wave conduction in the heart is strongly related to the proper interplay between the electrophysiological activation and mechanical contraction of myocytes and extracellular matrix (ECM) properties. In this study, we statistically compare bioengineered cardiac tissues cultured on soft hydrogels (E ≃ 12 kPa) and rigid glass substrates by focusing on the critical threshold of alternans, network-physiological tissue properties, and the formation of stable spiral waves that manifest after wave breakups. For the classification of wave dynamics, we use an improved signal oversampling technique and introduce simple probability maps to identify and visualize spatially concordant and discordant alternans as V- and X-shaped probability distributions. We found that cardiac tissues cultured on ECM-mimicking soft hydrogels show a lower variability of the calcium transient durations among cells in the tissue. This lowers the likelihood of forming stable spiral waves because of the larger dynamical range that tissues can be stably entrained with to form alternans and larger spatial spiral tip movement that increases the chance of selftermination on the tissue boundary. Conclusively, we show that a dysfunction in the excitation-contraction coupling dynamics facilitates life-threatening arrhythmic states such as spiral waves and, thus, highlights the importance of the network-physiological interplay between contractile myocytes and the ECM. [ABSTRACT FROM AUTHOR]

The spinal cord is of fundamental importance for integrative processing in brain–body communication, yet routine noninvasive recordings in humans are hindered by vast methodological challenges. Here, we overcome these challenges by developing an easy-to-use electrophysiological approach based on high-density multichannel spinal recordings combined with multivariate spatial-filtering analyses. These advances enable a spatiotemporal characterization of spinal cord responses and demonstrate a sensitivity that permits assessing even single-trial responses. To furthermore enable the study of integrative processing along the neural processing hierarchy in somatosensation, we expand this approach by simultaneous peripheral, spinal, and cortical recordings and provide direct evidence that bottom-up integrative processing occurs already within the spinal cord and thus after the first synaptic relay in the central nervous system. Finally, we demonstrate the versatility of this approach by providing noninvasive recordings of nociceptive spinal cord responses during heat-pain stimulation. Beyond establishing a new window on human spinal cord function at millisecond timescale, this work provides the foundation to study brain–body communication in its entirety in health and disease. Whilst spinal recording techniques are routinely developed for use in experimental animals, methods to interrogate human spinal cord function are lacking. These authors develop a non-invasive electrospinography approach that can directly record spinal cord activity with high precision. [ABSTRACT FROM AUTHOR]

Primary visual cortex (V1) has been the focus of extensive neurophysiological investigations, with its laminar organization serving as a crucial model for understanding the functional logic of neocortical microcircuits. Utilizing newly developed highdensity, Neuropixels probes, we measured visual responses from large populations of simultaneously recorded neurons distributed across layers of macaque V1. Within single recordings, myriad differences in the functional properties of neuronal subpopulations could be observed. Notably, while standard measurements of orientation selectivity showed only minor differences between laminar compartments, decoding stimulus orientation from layer 4C responses outperformed both superficial and deep layers within the same cortical column. The superior orientation discrimination within layer 4C was associated with greater response reliability of individual neurons rather than lower correlated activity within neuronal populations. Our results underscore the efficacy of high-density electrophysiology in revealing the functional organization and network properties of neocortical microcircuits within single experiments. [ABSTRACT FROM AUTHOR]