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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]

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]

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]

[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]

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]

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]

Smart clothes equipped with flexible sensing systems provide a comfortable means to track health status in real time. Although these sensors are flexible and small, the core signal-processing units still rely on a conventional printed circuit board (PCB), making current health-monitoring devices bulky and inconvenient to wear. In this study, a printed fabric-based hybrid circuit was designed and prepared—with a series of characteristics, such as surface/sectional morphology, electrical properties, and stability—to study its reliability. Furthermore, to verify the function of the fabric-based circuit, simulations and measurements of the circuit, as well as the collection and processing of a normal adult's electrophysiological signals, were conducted. Under 10,000 stretching and bending cycles with a certain elongation and bending angle, the resistance remained 0.27 Ω/cm and 0.64 Ω/cm, respectively, demonstrating excellent conductivity and reliability. Additionally, the results of the simulation and experiment showed that the circuit can successfully amplify weak electrocardiogram (ECG) signals with a magnification of 1600 times with environmental filtering and 50 Hz of industrial frequency interference. This technology can monitor human electrophysiological signals, such as ECGs, electromyograms (EMGs), and joint motion, providing valuable practical guidance for the unobtrusive monitoring of smart clothes. [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]

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]

It is well established that holding information in working memory (WM) elicits sustained stimulus-specific patterns of neural activity. Nevertheless, here we provide evidence for a distinct class of neural activity that tracks the number of individuated items in working memory, independent of the type of visual features stored. We present two EEG studies of young adults of both sexes that provide robust evidence for a signal tracking the number of individuated representations in working memory, regardless of the specific feature values stored. In Study 1, subjects maintained either colors or orientations across separate blocks in a single session. We found near-perfect generalization of the load signal between these two conditions, despite being able to simultaneously decode which feature had been voluntarily stored. In Study 2, participants attended to two features with very distinct cortical representations: color and motion coherence. We again found evidence for a neural load signal that robustly generalized across these distinct visual features, even though cortically disparate regions process color and motion coherence. Moreover, representational similarity analysis provided converging evidence for a content-independent load signal, while simultaneously showing that unique variance in EEG activity tracked the specific features that were stored. We posit that this load signal reflects a content-independent “pointer” operation that binds objects to the current context while parallel but distinct neural signals represent the features that are stored for each item in memory. [ABSTRACT FROM AUTHOR]

Calcium homeostasis modulators (CALHMs) are the most recently discovered members of the large‐pore channel family. They mediate the conductance of ions and larger molecules, such as ATP, and play critical roles in pathways related to Alzheimer's disease, neuroinflammation, neuromodulation, taste perception and innate immune responses. Since the inaugural report on CALHM1 in 2008, significant breakthroughs have revealed their biological roles, ion and ATP channel functions, and structures, positioning the field for further advancements. In this review, we discuss the overall progress and recent developments in understanding the biological roles, functions and molecular structures of CALHM proteins. [ABSTRACT FROM AUTHOR]

Summary Clozapine is effective in treatment‐resistant schizophrenia but with adverse effects including sedation. Excessive daytime sleepiness, a symptom of hypersomnolence, is the most frequently reported subjective side‐effect. The aim of this systematic review was to synthesise the literature evaluating the impact of clozapine on the objective assessment of hypersomnolence in people with schizophrenia. We systematically searched databases for articles evaluating hypersomnolence with electrophysiological or psychomotor/cognitive measures in clozapine‐treated patients with schizophrenia. Objective assessment of hypersomnolence was evaluated in six studies. All studies using polysomnography (PSG) found significantly longer total sleep time and shorter sleep onset latency in patients treated with clozapine at initiation of clozapine. The study with the multiple sleep latency test (MSLT) also found a shorter sleep onset latency. These observations did not persist 4–6 weeks after treatment initiation. Further investigations are needed. Longer total sleep time should be investigated with standardised long‐term PSG to investigate excessive sleep quantity. Shorter sleep onset latency should be investigated with the MSLT or the maintenance of wakefulness test to investigate the excessive propensity to fall asleep or ability to stay awake. Lastly, sleep inertia should be investigated specifically in the morning. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Orthostatic tremor (OT) is a rare movement disorder characterized by a feeling of unsteadiness and a high‐frequency tremor in the legs (13–18 Hz) relieved by sitting or walking.The aims were to study the brain electrophysiology captured chronically in a person with medication‐refractory OT while standing and walking and in the semi‐recumbent position using bilateral ventral intermedius nucleus deep brain stimulation (DBS) (Medtronic Percept PC) and to describe the clinical use of closed‐loop DBS.A sensing survey was used to capture baseline local field potentials (LFPs) while standing. Livestreamed LFPs were synchronized with data collected from two accelerometers (legs) and gait analysis during OFF stimulation and continuous and closed‐loop DBS.Strong oscillatory coupling between thalamic LFP and leg tremor with significant coherence at 14.65 Hz was found during weight‐bearing. Single‐threshold adaptive DBS (sensing at this frequency) was superior to continuous stimulation in reducing tremor and stimulation‐related gait ataxia.This study provides new insights into both the pathophysiology and management of OT. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Striatum and its predominant input, motor cortex, are responsible for the selection and performance of purposive movement, but how their interaction guides these processes is not understood. To establish its neural and behavioral contributions, we bilaterally lesioned motor cortex and recorded striatal activity and reaching performance daily, capturing the lesion's direct ramifications within hours of the intervention. We observed reaching impairment and an absence of striatal motoric activity following lesion of motor cortex, but not parietal cortex control lesions. Although some aspects of performance began to recover after 8–10 days, striatal projection and interneuronal dynamics did not—eventually entering a non-motor encoding state that aligned with persisting kinematic control deficits. Lesioned mice also exhibited a profound inability to switch motor plans while locomoting, reminiscent of clinical freezing of gait (FOG). Our results demonstrate the necessity of motor cortex in generating trained and untrained actions as well as striatal motoric dynamics. [Display omitted] • Motor, but not parietal, cortex is necessary for performing goal-directed actions • Movement-related dynamics in the striatum are absent following lesions of M1 • Behavior and striatal activity partly recover but are not comparable to pre-lesion • M1 lesions cause freezing of gait, suggesting its role in motor-state regulation Nicholas and Yttri find that in the absence of motor cortex, the stratum alone is not capable of producing goal-directed behavior. Lesions of motor cortex also produce a freezing of gait-like behavior, implicating motor cortex in the setting and updating of motor state. [ABSTRACT FROM AUTHOR]

Two-pore domain potassium (K2P) channels play a central role in modulating cellular excitability and neuronal function. The unique structure of the selectivity filter in K2P and other potassium channels determines their ability to allow the selective passage of potassium ions across cell membranes. The nematode C. elegans has one of the largest K2P families, with 47 subunit-coding genes. This remarkable expansion has been accompanied by the evolution of atypical selectivity filter sequences that diverge from the canonical TxGYG motif. Whether and how this sequence variation may impact the function of K2P channels has not been investigated so far. Here, we show that the UNC-58 K2P channel is constitutively permeable to sodium ions and that a cysteine residue in its selectivity filter is responsible for this atypical behavior. Indeed, by performing in vivo electrophysiological recordings and Ca2+ imaging experiments, we demonstrate that UNC-58 has a depolarizing effect in muscles and sensory neurons. Consistently, unc-58 gain-of-function mutants are hypercontracted, unlike the relaxed phenotype observed in hyperactive mutants of many neuromuscular K2P channels. Finally, by combining molecular dynamics simulations with functional studies in Xenopus laevis oocytes, we show that the atypical cysteine residue plays a key role in the unconventional sodium permeability of UNC-58. As predicting the consequences of selectivity filter sequence variations in silico remains a major challenge, our study illustrates how functional experiments are essential to determine the contribution of such unusual potassium channels to the electrical profile of excitable cells. [ABSTRACT FROM AUTHOR]

Quasi‐solid‐state thermocells (QTECs) show promise as a power source for wearable devices by converting body heat into electricity. While significant progress has been made with p‐type elements for QTECs, challenges remain with their n‐type counterparts. Here, a high‐performance n‐type QTEC element is presented, using a copolymer hydrogel that outperforms conventional p‐type elements. This copolymer hydrogel combines hydrophilic zwitterionic sulfobetaine methacrylate (SBMA) for ionic conduction and hydrophobic methyl methacrylate (MMA) for structural stability. By increasing the MMA content from 35 to 100 wt.%, versatile control is achieved over the hydrogel's elastic modulus (72 kPa to 127.7 MPa) and tensile strength (54 kPa to 6.7 MPa). A high mechanical toughness of 7.2 MJ m−3 is also achieved at 68 wt.% MMA. The mechanically robust and high toughness p(SBMA‐MMA) hydrogel is then immersed in Fe(ClO4)2/3 solutions of different concentrations to evaluate its performance as an n‐type QTEC element. The hydrogel with 0.8 M Fe(ClO4)2/3 exhibits a high ionic Seebeck coefficient of −1.7 mV K−1, a power density of 1.1 mW m−2 K−2, and an elastic modulus of 1.6 MPa, which is similar to that of human skin. Finally, the optimized n‐type p(SBMA‐MMA) hydrogels demonstrate the potential application for wearable devices. [ABSTRACT FROM AUTHOR]

Traditional microelectrode arrays (MEAs) are limited to measuring electrophysiological activity in two dimensions, failing to capture the complexity of three-dimensional (3D) tissues such as neural organoids and spheroids. Here, we introduce a flower-shaped MEA (e-Flower) that can envelop submillimeter brain spheroids following actuation by the sole addition of the cell culture medium. Inspired by soft microgrippers, its actuation mechanism leverages the swelling properties of a polyacrylic acid hydrogel grafted to a polyimide substrate hosting the electrical interconnects. Compatible with standard electrophysiology recording systems, the e-Flower does not require additional equipment or solvents and is ready to use with preformed 3D tissues. We designed an e-Flower achieving a curvature as low as 300 micrometers within minutes, a value tunable by the choice of reswelling media and hydrogel cross-linker concentration. Furthermore, we demonstrate the ability of the e-Flower to detect spontaneous neural activity across the spheroid surface, demonstrating its potential for comprehensive neural signal recording. [ABSTRACT FROM AUTHOR]

Background: Myopia-26, a Mendelian form of early-onset high-myopia (eoHM) caused by mutations in the X-chromosomal ARR3 gene and predominantly affecting females, curiously, may provide an alternative route of investigation to unveil retinal mechanisms underlying pathological eye growth. We conducted a case-control cross-sectional prospective electrophysiological study in genetically characterized Myopia-26 patients (ARR3 heterozygous symptomatic females) compared with high myopes harboring intact ARR3 alleles and one carrier hemizygous male. Results: Participants were 26 volunteers: 10 healthy control females (E-CTRL, mean age = 31.5 ± 8.8 years), one healthy control male, one carrier male of the mutant ARR3 allele and 14 female eoHM patients (mean age = 27.0 ± 13.1 years) divided in two groups: seven without (M-CTRL) and seven with (MYP-26) genetic alteration in the ARR3 gene. The clinical evaluation included complete eye screening and full-field electroretinograms (ERGs) recorded from both eyes under mydriasis. Spherical equivalent was comparable (mean=-9.55 ± 2.46 and − 10.25 ± 3.22 for M-CTRL and MYP-26, respectively) and best corrected visual acuity (BCVA) was significantly different between M-CTRL and MYP-26 (1.0 vs. 0.406 ± 0.253, respectively). E-CTRL and M-CTRL showed similar light-adapted flash and flicker ERG amplitudes; however, the prior values were reduced by ~ 35% (a- and b-waves alike), the latter by ~ 55% in the MYP-26 group (F(2, 45) > 21.821, p < 0.00001). Dark-adapted a-wave amplitudes were slightly reduced (by ~ 20%) in all myopic patients compared to E-CTRL, irrespective of the ARR3 genotype (E-CTRL vs. eoHM, p = 0.038). Conclusions: The cone dysfunction observed in Myopia-26 patients is specifically linked to the mutation of ARR3, and is not the consequence of eoHM, i.e. elongation of the eye. It may play a role in myopic refractive error development through a yet unconfirmed pathomechanism. [ABSTRACT FROM AUTHOR]

The hippocampus has a crucial role in the formation, consolidation and recall of memories as well as in navigation related processes. These functions are in the focus of neuroscience and different disciplines have contributed to this research field for decades. Two-photon imaging in awake animals is a valuable new aspect for these observations, especially when it is supported by electrophysiology. In this study, we applied high speed two-photon hippocampal imaging through a chronically implanted, soft, transparent microelectrode (STM) device incorporated into a cranial window chamber in awake mice. We monitored the impedance of the recording sites over the course of the experiments to observe long-term changes in recording quality. The large-scale ipsilateral local field potential (LFP) recordings from the dorsal hippocampus provided reliable sharp wave-ripples (SPW-Rs), multi-unit activity (MUA) and single-unit activity (SUA) for up to two months. Calcium imaging of GCaMP6f. labeled cells from the CA1 pyramidal layer under the transparent device was possible even after six months in thy1-GCaMP6f. transgenic mice. We investigated the immune response with GFAP staining after the end of the long-term experiments. Based on our results, this dedicated transparent electrode device proved to be suitable for simultaneous two-photon imaging and large-scale electrophysiological measurements in chronic experiments in mice. [ABSTRACT FROM AUTHOR]

With mounting evidence for the benefits of meditation, there has been a growing interest in measuring and quantifying meditative states. This study introduces the Inner Dereification Index (IDI), a class of personalized models designed to quantify the distance from non-meditative states such as mind wandering based on a single individual's neural activity. In addition to demonstrating high classification accuracy (median AUC: 0.996) at distinguishing meditation from thinking states moment by moment, IDI can accurately stratify meditator cohorts by experience, and correctly identify the practices most effective at training the dereification aspect of meditation (decentering from immersion with thoughts and perceptions and recognizing them as mental constructs). These results suggest that IDI models may be a useful real-time proxy for dereification and meditation progress, requiring only 1 min of mind wandering data (and no meditation data) during model training. Thus, they show promise for applications such as real-time meditation feedback, progress tracking, personalization of practices, and potential therapeutic applications of neurofeedback-assisted generation of positive states of consciousness. [ABSTRACT FROM AUTHOR]

Excitatory glutamatergic NMDA receptors (NMDARs) are key regulators of spinal pain processing, and yet the biophysical properties of NMDARs in dorsal horn nociceptive neurons remain poorly understood. Despite the clinical implications, it is unknown whether the molecular and functional properties of synaptic NMDAR responses are conserved between males and females or translate from rodents to humans. To address these translational gaps, we systematically compared individual and averaged excitatory synaptic responses from lamina I pain‐processing neurons of adult Sprague–Dawley rats and human organ donors, including both sexes. By combining patch‐clamp recordings of outward miniature excitatory postsynaptic currents with non‐biased data analyses, we uncovered a wide range of decay constants of excitatory synaptic events within individual lamina I neurons. Decay constants of synaptic responses were distributed in a continuum from 1–20 ms to greater than 1000 ms, suggesting that individual lamina I neurons contain AMPA receptor (AMPAR)‐only as well as GluN2A‐, GluN2B‐ and GluN2D‐NMDAR‐dominated synaptic events. This intraneuronal heterogeneity in AMPAR‐ and NMDAR‐mediated decay kinetics was observed across sex and species. However, we discovered an increased relative contribution of GluN2A‐dominated NMDAR responses at human lamina I synapses compared with rodent synapses, suggesting a species difference relevant to NMDAR subunit‐targeting therapeutic approaches. The conserved heterogeneity in decay rates of excitatory synaptic events within individual lamina I pain‐processing neurons may enable synapse‐specific forms of plasticity and sensory integration within dorsal horn nociceptive networks. Key points: Synaptic NMDA receptors (NMDARs) in spinal dorsal horn nociceptive neurons are key regulators of pain processing, but it is unknown whether their functional properties are conserved between males and females or translate from rodents to humans.In this study, we compared individual excitatory synaptic responses from lamina I pain‐processing neurons of male and female adult Sprague–Dawley rats and human organ donors.Individual lamina I neurons from male and female rats and humans contain AMPA receptor‐only as well as GluN2A, GluN2B‐ and GluN2D‐NMDAR‐dominated synaptic events. This may enable synapse‐specific forms of plasticity and sensory integration within dorsal horn nociceptive networks.Human lamina I synapses have an increased relative contribution of GluN2A‐dominated NMDAR responses compared with rodent synapses.These results uncover a species difference relevant to NMDAR subunit‐targeting therapeutic approaches. [ABSTRACT FROM AUTHOR]

Consciousness, defined as being aware of and responsive to one's surroundings, is characteristic of normal waking life and typically is lost during sleep and general anaesthesia. The traditional view of consciousness as a global brain state has evolved toward a more sophisticated interplay between global and local states, with the presence of local sleep in the awake brain and local wakefulness in the sleeping brain. However, this interplay is not clear for general anaesthesia, where loss of consciousness was recently suggested to be associated with a global state of brain‐wide synchrony that selectively involves layer 5 cortical pyramidal neurons across sensory, motor and associative areas. According to this global view, local wakefulness of layer 5 cortex should be incompatible with deep anaesthesia, a hypothesis that deserves to be scrutinised with causal manipulations. Here, we show that unilateral chemogenetic activation of layer 5 pyramidal neurons in the sensorimotor cortex of isoflurane‐anaesthetised mice induces a local state transition from slow‐wave activity to tonic firing in the transfected hemisphere. This wakefulness‐like activity dramatically disrupts layer 5 interhemispheric synchrony with mirror‐image locations in the contralateral hemisphere, but does not reduce the level of unconsciousness under deep anaesthesia, nor in the transitions to/from anaesthesia. Global layer 5 synchrony may thus be a sufficient condition for anaesthesia‐induced unconsciousness, but is not a necessary one, at least under isoflurane anaesthesia. Local wakefulness‐like activity of layer 5 cortex can be induced and maintained under deep anaesthesia, encouraging further investigation into the local vs. global aspects of anaesthesia‐induced unconsciousness. Key points: The neural correlates of consciousness have evolved from global brain states to a nuanced interplay between global and local states, evident in terms of local sleep in awake brains and local wakefulness in sleeping brains.The concept of local wakefulness remains unclear for general anaesthesia, where the loss of consciousness has been recently suggested to involve brain‐wide synchrony of layer 5 cortical neurons.We found that local wakefulness‐like activity of layer 5 cortical can be chemogenetically induced in anaesthetised mice without affecting the depth of anaesthesia or the transitions to and from unconsciousness.Global layer 5 synchrony may thus be a sufficient but not necessary feature for the unconsciousness induced by general anaesthesia.Local wakefulness‐like activity of layer 5 neurons is compatible with general anaesthesia, thus promoting further investigation into the local vs. global aspects of anaesthesia‐induced unconsciousness. [ABSTRACT FROM AUTHOR]

All new drugs must go through preclinical screening tests to determine their proarrhythmic potential. While these assays effectively filter out dangerous drugs, they are too conservative, often misclassifying safe compounds as proarrhythmic. In this study, we attempt to address this shortcoming with a novel, medium‐throughput drug‐screening approach: we use an automated patch‐clamp system to acquire optimized voltage clamp (VC) and action potential (AP) data from human induced pluripotent stem cell‐derived cardiomyocytes (iPSC‐CMs) at several drug concentrations (baseline, 3×, 10× and 20× the effective free plasma concentrations). With our novel method, we show correlations between INa block and upstroke slowing after treatment with flecainide or quinine. Additionally, after quinine treatment, we identify significant reductions in current during voltage steps designed to isolate If and IKs. However, we do not detect any IKr block by either drug, and upon further investigation, do not see any IKr present in the iPSC‐CMs when prepared for automated patch experiments (i.e. in suspension) – this is in contrast to similar experiments we have conducted with these cells using the manual patch setup. In this study, we: (1) present a proof‐of‐concept demonstration of a single‐cell medium‐throughput drug study, and (2) characterize the non‐canonical electrophysiology of iPSC‐CMs when prepared for experiments in a medium‐throughput setting. Key points: Human induced pluripotent stem cell‐derived cardiomyocytes (iPSC‐CMs) offer potential as an in vitro model to study the proarrhythmic potential of drugs, but insights from these cells are often limited by the low throughput of manual patch‐clamp.In this study, we use a medium‐throughput automated patch‐clamp system to acquire action potential (AP) and complex voltage clamp (VC) data from single iPSC‐CMs at multiple drug concentrations.A correlation between AP upstroke and INa transients was identified and drug‐induced changes in ionic currents found.We also characterize the substantially altered physiology of iPSC‐CMs when patched in an automated system, suggesting the need to investigate differences between manual and automated patch experiments. [ABSTRACT FROM AUTHOR]