Auditory stimulation during REM sleep modulates REM electrophysiology and cognitive performance.

REM sleep is critical for memory, emotion, and cognition. Manipulating brain activity during REM could improve our understanding of its function and benefits. Earlier studies have suggested that auditory stimulation in REM might modulate REM time and reduce rapid eye movement density. Building on this, we studied the cognitive effects and electroencephalographic responses related to such stimulation. We used acoustic stimulation locked to eye movements during REM and compared two overnight conditions (stimulation and no-stimulation). We evaluated the impact of this stimulation on REM sleep duration and electrophysiology, as well as two REM-sensitive memory tasks: visual discrimination and mirror tracing. Our results show that this auditory stimulation in REM decreases the rapid eye movements that characterize REM sleep and improves performance on the visual task but is detrimental to the mirror tracing task. We also observed increased beta-band activity and decreased theta-band activity following stimulation. Interestingly, these spectral changes were associated with changes in behavioural performance. These results show that acoustic stimulation can modulate REM sleep and suggest that different memory processes underpin its divergent impacts on cognitive performance.

Effect of ubiquinol on electrophysiology during high-altitude acclimatization and de-acclimatization: A substudy of the Shigatse CARdiorespiratory fitness (SCARF) randomized clinical trial.

BACKGROUND: High-altitude exposure changes the electrical conduction of the heart. However, reports on electrocardiogram (ECG) characteristics and potent prophylactic agents during high-altitude acclimatization and de-acclimatization are inadequate. This study aimed to investigate the effects of ubiquinol on electrophysiology after high-altitude hypoxia and reoxygenation. METHODS: The study was a prospective, randomized, double-blind, placebo-controlled trial. Forty-one participants were randomly divided into two groups receiving ubiquinol 200 mg daily or placebo orally 14 days before flying to high altitude (3900 m) until the end of the study. Cardiopulmonary exercise testing was performed at baseline (300 m), on the third day after reaching high altitude, and on the seventh day after returning to baseline. RESULTS: Acute high-altitude exposure prolonged resting ventricular repolarization, represented by increased corrected QT interval (455.9 ± 23.4 vs. 427.1 ± 19.1 ms, P < 0.001) and corrected Tpeak-Tend interval (155.5 ± 27.4 vs. 125.3 ± 21.1 ms, P < 0.001), which recovered after returning to low altitude. Ubiquinol supplementation shortened the hypoxia-induced extended Tpeak-Tend interval (-7.7 ms, [95% confidence interval (CI), -13.8 to -1.6], P = 0.014), Tpeak-Tend /QT interval (-0.014 [95% CI, -0.027 to -0.002], P = 0.028), and reserved maximal heart rate (11.9 bpm [95% CI, 3.2 to 20.6], P = 0.013) during exercise at high altitude. Furthermore, the decreased resting amplitude of the ST-segment in the V3 lead was correlated with decreased peak oxygen pulse (R = 0.713, P < 0.001) and maximum oxygen consumption (R = 0.595, P < 0.001). CONCLUSIONS: Our results illustrated the electrophysiology changes during high-altitude acclimatization and de-acclimatization. Similarly, ubiquinol supplementation shortened the prolonged Tpeak-Tend interval and reserved maximal heart rate during exercise at high altitude. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2200059900.

Anaesthetic management of paediatric patients undergoing electrophysiology study and ablation for supraventricular tachycardia: A focused narrative review.

Every year, 80,000-100,000 ablation procedures take place in the United States and approximately 1% of these involve paediatric patients. As the paediatric population undergoing catheter ablation to treat dysrhythmia is constantly growing, involvement of anaesthesiologists in the cardiac electrophysiology laboratory is simultaneously increasing. Compared with the adult population, paediatric patients need deeper sedation or general anaesthesia (GA) to guarantee motionlessness and preserve comfort. As a result, the anaesthesiologist working in this setting should keep in mind heart physiopathology as well as possible interactions between anaesthetic drugs and arrhythmia. In fact, drug-induced suppression of accessory pathways (APs) conduction capacity is a major concern for completing a successful electrophysiology study (EPS). Nevertheless, the literature on this topic is scarce and the optimal type of anaesthesia in EPS and ablation procedures in children is still controversial. Thus, the main goal of the present review is to collect the literature published so far on the effects on cardiac conduction tissue of the drugs commonly employed for sedation/GA in the cath lab for EPS and ablation procedures to treat supraventricular tachycardia in patients aged <18 years.

A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons.

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for 'gain setting' of brain-spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.

Utilization of Regional Anesthesia in the Electrophysiology Lab: A Narrative Review.

PURPOSE OF REVIEW: The electrophysiology lab is an important source of growth of anesthetic volume as the indications and evidence for catheter ablations and various cardiac implantable electronic devices improve. Paired with this increase in volume is an increasing number of patients with substantial comorbid conditions presenting for their EP procedures. For these patients, the interaction between their comorbidities and traditional anesthesia practices may create the risk of hemodynamic instability, cardiovascular or respiratory complications, and potential need for prolonged post-operative monitoring negatively impacting length of hospital stay. RECENT FINDINGS: Regional anesthetic techniques, including pectoralis, serratus, and erector spinae plane blocks, offer options for both regional analgesia and surgical anesthesia for a variety of EP procedures. Existing case reports and extrapolations from other areas support these techniques as viable, safe, and effective components of an anesthetic plan. In this article, we will review the development and challenges of various EP procedures and how different regional anesthetic techniques can function as a component of the anesthesia plan.

Proglucagon signalling in the rat Dorsomedial Hypothalamus - Physiology and high-fat diet-mediated alterations.

A relatively new pharmacological target in obesity treatment has been the preproglucagon (PPG) signalling, predominantly with glucagon-like peptide (GLP) 1 receptor agonists. As far as the PPG role within the digestive system is well recognised, its actions in the brain remain understudied. Here, we investigated PPG signalling in the Dorsomedial Hypothalamus (DMH), a structure involved in feeding regulation and metabolism, using in situ hybridisation, electrophysiology, and immunohistochemistry. Our experiments were performed on animals fed both control, and high-fat diet (HFD), uncovering HFD-mediated alterations. First, sensitivity to exendin-4 (Exn4, a GLP1R agonist) was shown to increase under HFD, with a higher number of responsive neurons. The amplitude of the response to both Exn4 and oxyntomodulin (Oxm) was also altered, diminishing its relationship with the cells' spontaneous firing rate. Not only neuronal sensitivity, but also GLP1 presence, and therefore possibly release, was influenced by HFD. Immunofluorescent labelling of the GLP1 showed changes in its density depending on the metabolic state (fasted/fed), but this effect was eliminated by HFD feeding. Interestingly, these dietary differences were absent after a period of restricted feeding, allowing for an anticipation of the alternating metabolic states, which suggests possible prevention of such outcome.

Experimental Verification for Numerical Simulation of Thalamic Stimulation-Evoked Calcium-Sensitive Fluorescence and Electrophysiology with Self-Assembled Multifunctional Optrode.

Owing to its capacity to eliminate a long-standing methodological limitation, fiber photometry can assist research gaining novel insight into neural systems. Fiber photometry can reveal artifact-free neural activity under deep brain stimulation (DBS). Although evoking neural potential with DBS is an effective method for mediating neural activity and neural function, the relationship between DBS-evoked neural Ca2+ change and DBS-evoked neural electrophysiology remains unknown. Therefore, in this study, a self-assembled optrode was demonstrated as a DBS stimulator and an optical biosensor capable of concurrently recording Ca2+ fluorescence and electrophysiological signals. Before the in vivo experiment, the volume of tissue activated (VTA) was estimated, and the simulated Ca2+ signals were presented using Monte Carlo (MC) simulation to approach the realistic in vivo environment. When VTA and the simulated Ca2+ signals were combined, the distribution of simulated Ca2+ fluorescence signals matched the VTA region. In addition, the in vivo experiment revealed a correlation between the local field potential (LFP) and the Ca2+ fluorescence signal in the evoked region, revealing the relationship between electrophysiology and the performance of neural Ca2+ concentration behavior. Concurrent with the VTA volume, simulated Ca2+ intensity, and the in vivo experiment, these data suggested that the behavior of neural electrophysiology was consistent with the phenomenon of Ca2+ influx to neurons.

Effects of hydroxychloroquine on atrial electrophysiology in in silico wild-type and PITX2+/- atrial cardiomyocytes.

BACKGROUND: Hydroxychloroquine (HCQ) is commonly used in the treatment of autoimmune diseases and increases the risk of QT interval prolongation. However, it is unclear how HCQ affects atrial electrophysiology and the risk of atrial fibrillation (AF). METHODS: We quantitatively examined the potential atrial arrhythmogenic effects of HCQ on AF using a computational model of human atrial cardiomyocytes. We measured atrial electrophysiological markers after systematically varying HCQ concentrations. RESULTS: The HCQ concentrations were positively correlated with the action potential duration (APD), resting membrane potential, refractory period, APD alternans threshold, and calcium transient alternans threshold (p < 0.05). By contrast, HCQ concentrations were inversely correlated with the maximum upstroke velocity and calcium transient amplitude (p < 0.05). When the therapeutic concentration (Cmax) of HCQ was applied, HCQ increased APD90 by 1.4% in normal sinus rhythm, 1.8% in wild-type AF, and 2.6% in paired-like homeodomain transcription factor 2 (PITX2)+/- AF, but did not affect the alternans thresholds. The overall in silico results suggest no significant atrial arrhythmogenic effects of HCQ at Cmax, instead implying a potential antiarrhythmic role of low-dose HCQ in AF. However, at an HCQ concentration of fourfold Cmax, a rapid pacing rate of 4 Hz induced prominent APD alternans, particularly in the PITX2+/- AF model. CONCLUSION: Our in silico analysis suggests a potential antiarrhythmic role of low-dose HCQ in AF. Concomitant PITX2 mutations and high-dose HCQ treatments may increase the risk of AF, and this potential genotype/dose-dependent arrhythmogenic effect of HCQ should be investigated further.

Modeling relationships between iron status, behavior, and brain electrophysiology: evidence from a randomized study involving a biofortified grain in Indian adolescents.

BACKGROUND: Iron deficiency (ID) and iron deficiency anemia (IDA) are highly-prevalent nutrient deficiencies and have been shown to have a range of negative effects on cognition and brain function. Human intervention studies including measures at three levels-blood, brain, and behavior-are rare and our objective was to model the relationships among measures at these three levels in school-going Indian adolescents. METHODS: Male and female adolescents in rural India were screened for ID/IDA. Subjects consumed 2 meals/day for 6 months; half were randomly assigned to consume meals made from a standard grain (pearl millet) and half consumed meals made from an iron biofortified pearl millet (BPM). Prior to and then at the conclusion of the feeding trial, they completed a set of cognitive tests with concurrent electroencephalography (EEG). RESULTS: Overall, serum ferritin (sFt) levels improved over the course of the study. Ten of 21 possible measures of cognition showed improvements from baseline (BL) to endline (EL) that were larger for those consuming BPM than for those consuming the comparison pearl millet (CPM). Critically, the best model for the relationship between change in iron status and change in cognition had change in brain measures as a mediating factor, with both change in serum ferritin as a primary predictor and change in hemoglobin as a moderator. CONCLUSIONS: A dietary intervention involving a biofortified staple grain was shown to be efficacious in improving blood iron biomarkers, behavioral measures of cognition, and EEG measures of brain function. Modeling the relationships among these variables strongly suggests multiple mechanisms by which blood iron level affects brain function and cognition. TRIAL REGISTRATION: Registered at ClinicalTrials.gov, NCT02152150 , 02 June 2014.

Neural mechanisms underlying psilocybin's therapeutic potential - the need for preclinical in vivo electrophysiology.

Psilocybin is a naturally occurring psychedelic compound with profound perception-, emotion- and cognition-altering properties and great potential for treating brain disorders. However, the neural mechanisms mediating its effects require in-depth investigation as there is still much to learn about how psychedelic drugs produce their profound and long-lasting effects. In this review, we outline the current understanding of the neurophysiology of psilocybin's psychoactive properties, highlighting the need for additional preclinical studies to determine its effect on neural network dynamics. We first describe how psilocybin's effect on brain regions associated with the default-mode network (DMN), particularly the prefrontal cortex and hippocampus, likely plays a key role in mediating its consciousness-altering properties. We then outline the specific receptor and cell types involved and discuss contradictory evidence from neuroimaging studies regarding psilocybin's net effect on activity within these regions. We go on to argue that in vivo electrophysiology is ideally suited to provide a more holistic, neural network analysis approach to understand psilocybin's mode of action. Thus, we integrate information about the neural bases for oscillatory activity generation with the accumulating evidence about psychedelic drug effects on neural synchrony within DMN-associated areas. This approach will help to generate important questions for future preclinical and clinical studies. Answers to these questions are vital for determining the neural mechanisms mediating psilocybin's psychotherapeutic potential, which promises to improve outcomes for patients with severe depression and other difficulty to treat conditions.

The Direction of response selectivity between conspecific and heterospecific auditory stimuli varies with response metric.

Species recognition is an essential behavioral outcome of social discrimination, flocking, mobbing, mating, and/or parental care. In songbirds, auditory species recognition cues are processed through specialized forebrain circuits dedicated to acoustic discrimination. Here we addressed the direction of behavioral and neural metrics of zebra finches' (Taeniopygia guttata) responses to acoustic cues of unfamiliar conspecifics vs. heterospecifics. Behaviorally, vocal response rates were greater for conspecific male zebra finch songs over heterospecific Pin-tailed Whydah (Vidua macroura) songs, which paralleled greater multiunit spike rates in the auditory forebrain in response to the same type of conspecific over heterospecific auditory stimuli. In contrast, forebrain activation levels were reversed to species-specific song playbacks during two functional magnetic resonance imaging experiments: we detected consistently greater responses to whydah songs over finch songs and did so independently of whether subjects had been co-housed or not with heterospecifics. These results imply that the directionality of behavioral and neural response selectivity metrics are not always consistent and appear to be experience-independent in this set of stimulus-and-subject experimental paradigms.

Transesophageal electrophysiology study in the diagnosis of dual atrioventricular nodal nonreentrant tachycardia.

"Double fire" is generally characterized by 1:2 atrioventricular conduction of sinus beats traveling down fast and slow pathways that result in double ventricular response. When this phenomenon repeats rapidly, dual atrioventricular nodal nonreentrant tachycardia (DAVNNT) occurs. We report a case of an irregular tachycardia with a comprehensive record that includes an electrocardiogram, a transesophageal electrophysiology study, and an intracardiac electrophysiology study. This is the first report of transesophageal electrophysiology study in the diagnosis of DAVNNT. A diagnosis of DAVNNT was deduced, and the patient was successfully treated with radiofrequency ablation of the slow pathway.

Quantitative assays to measure the transport activity of the mitochondrial calcium uniporter in cell lines or Xenopus oocytes.

The mitochondrial calcium uniporter, which mediates mitochondrial Ca2+ uptake, regulates key cellular functions, including intracellular Ca2+ signaling, cell-fate determination, and mitochondrial bioenergetics. Here, we describe two complementary strategies to quantify the uniporter's transport activity. First, we detail a mitochondrial Ca2+ radionuclide uptake assay in cultured cell lines. Second, we describe electrophysiological recordings of the uniporter expressed in Xenopus oocytes. These approaches enable a detailed kinetic analysis of the uniporter to link its molecular properties to physiological functions. For complete details on the use and execution of this protocol, please refer to Tsai and Tsai (2018) and Phillips et al. (2019).

Neural correlates of acoustic dissonance in music: The role of musicianship, schematic and veridical expectations.

In western music, harmonic expectations can be fulfilled or broken by unexpected chords. Musical irregularities in the absence of auditory deviance elicit well-studied neural responses (e.g. ERAN, P3, N5). These responses are sensitive to schematic expectations (induced by syntactic rules of chord succession) and veridical expectations about predictability (induced by experimental regularities). However, the cognitive and sensory contributions to these responses and their plasticity as a result of musical training remains under debate. In the present study, we explored whether the neural processing of pure acoustic violations is affected by schematic and veridical expectations. Moreover, we investigated whether these two factors interact with long-term musical training. In Experiment 1, we registered the ERPs elicited by dissonant clusters placed either at the middle or the ending position of chord cadences. In Experiment 2, we presented to the listeners with a high proportion of cadences ending in a dissonant chord. In both experiments, we compared the ERPs of musicians and non-musicians. Dissonant clusters elicited distinctive neural responses (an early negativity, the P3 and the N5). While the EN was not affected by syntactic rules, the P3a and P3b were larger for dissonant closures than for middle dissonant chords. Interestingly, these components were larger in musicians than in non-musicians, while the N5 was the opposite. Finally, the predictability of dissonant closures in our experiment did not modulate any of the ERPs. Our study suggests that, at early time windows, dissonance is processed based on acoustic deviance independently of syntactic rules. However, at longer latencies, listeners may be able to engage integration mechanisms and further processes of attentional and structural analysis dependent on musical hierarchies, which are enhanced in musicians.

Efficiency of cell-type specific and generic promoters in transducing oxytocin neurons and monitoring their neural activity during lactation.

Hypothalamic oxytocin (OXT) and arginine-vasopressin (AVP) neurons have been at the center of several physiological and behavioral studies. Advances in viral vector biology and the development of transgenic rodent models have allowed for targeted gene expression to study the functions of specific cell populations and brain circuits. In this study, we compared the efficiency of various adeno-associated viral vectors in these cell populations and demonstrated that none of the widely used promoters were, on their own, effective at driving expression of a down-stream fluorescent protein in OXT or AVP neurons. As anticipated, the OXT promoter could efficiently drive gene expression in OXT neurons and this efficiency is solely attributed to the promoter and not the viral serotype. We also report that a dual virus approach using an OXT promoter driven Cre recombinase significantly improved the efficiency of viral transduction in OXT neurons. Finally, we demonstrate the utility of the OXT promoter for conducting functional studies on OXT neurons by using an OXT specific viral system to record neural activity of OXT neurons in lactating female rats across time. We conclude that extreme caution is needed when employing non-neuron-specific viral approaches/promoters to study neural populations within the paraventricular nucleus of the hypothalamus.

Assessment of cochlear electrophysiology in typically developing children and children with auditory processing disorder.

OBJECTIVE: Children with auditory processing disorder (APD) are reported to have abnormal auditory brainstem responses (ABR) but little is understood about their cochlear integrity. Poor cochlear integrity can affect neural responses. In this study, cochlear and auditory brainstem integrity was investigated in children with APD. METHOD: Twenty children with APD, sixteen typically developing children and twenty adults participated in this study. Click evoked electrocochleography (ECochG) and ABRs were recorded from all the participants. Cochlear responses were analyzed using a) latency and amplitude of summating potential; action potential, b) transmission time between summating potential and action potential, c) summating potential/action potential amplitude ratio and d) action potential latency difference to condensation and rarefaction polarity. Amplitude in the ABR components was examined. RESULTS: Children with APD showed similar cochlear function to the typically developing children. There were no significant differences in wave I amplitude between children with APD and typically developing children. However, wave V amplitude was significantly reduced in children with APD compared to typically developing children. CONCLUSION: In the absence of any functional differences in the cochlea, children with APD can show poor amplitude in the later components of the ABR. The ABR anomalies observed in children with APD arise due to poor neural processing, possibly after the first auditory synapse.

Time course for urethral neuromuscular reestablishment and its facilitated recovery by transcutaneous neuromodulation after simulated birth trauma in rats.

The aims of the study were to determine the time-course of urinary incontinence recovery after vaginal distension (VD), elucidate the mechanisms of injury from VD leading to external urethral sphincter (EUS) dysfunction, and assess if transcutaneous electrical stimulation (TENS) of the dorsal nerve of the clitoris facilitates recovery of urinary continence after VD. Rats underwent 4-h VD, 4-h sham VD (SH-VD), VD plus 1-h DNC TENS, and VD plus 1-h sham TENS (SH-TENS). TENS or SH-TENS were applied immediately and at days 2 and 4 post-VD. Micturition behavior, urethral histochemistry and histology, EUS and nerve electrophysiology, and cystometrograms were evaluated. VD induced urine leakage and significantly disrupted EUS fibers and nerve-conduction (VD vs SH-VD group; p < 0.01). Urine leakage disappeared 13 days post-VD (p < 0.001). Structural and functional recovery of EUS neuromuscular circuitry started by day 6 post-VD, but did not fully recover by day 11 post-VD (p > 0.05). TENS significantly decreased the frequency of urine leakage post-VD (days 5-7; p < 0.01). We conclude that rat urinary continence after VD requires 2 weeks to recover, although urethra structure is not fully recovered. TENS facilitated urinary continence recovery after VD. Additional studies are necessary to assess if TENS could be used in postpartum women.

Cochlear outer hair cell electromotility enhances organ of Corti motion on a cycle-by-cycle basis at high frequencies in vivo.

Mammalian hearing depends on an amplification process involving prestin, a voltage-sensitive motor protein that enables cochlear outer hair cells (OHCs) to change length and generate force. However, it has been questioned whether this prestin-based somatic electromotility can operate fast enough in vivo to amplify cochlear vibrations at the high frequencies that mammals hear. In this study, we measured sound-evoked vibrations from within the living mouse cochlea and found that the top and bottom of the OHCs move in opposite directions at frequencies exceeding 20 kHz, consistent with fast somatic length changes. These motions are physiologically vulnerable, depend on prestin, and dominate the cochlea's vibratory response to high-frequency sound. This dominance was observed despite mechanisms that clearly low-pass filter the in vivo electromotile response. Low-pass filtering therefore does not critically limit the OHC's ability to move the organ of Corti on a cycle-by-cycle basis. Our data argue that electromotility serves as the primary high-frequency amplifying mechanism within the mammalian cochlea.

Bioelectromagnetic Platform for Cell, Tissue, and In Vivo Stimulation.

Magnetogenetics is a new field that utilizes electromagnetic fields to remotely control cellular activity. In addition to the development of the biological genetic tools, this approach requires designing hardware with a specific set of demands for the electromagnets used to provide the desired stimulation for electrophysiology and imaging experiments. Here, we present a universal stimulus delivery system comprising four magnet designs compatible with electrophysiology, fluorescence and luminescence imaging, microscopy, and freely behaving animal experiments. The overall system includes a low-cost stimulation controller that enables rapid switching between active and sham stimulation trials as well as precise control of stimulation delivery thereby enabling repeatable and reproducible measurements.