The electrical heart axis of the fetus between 18 and 24 weeks of gestation: A cohort study

Introduction A fetal anomaly scan in mid-pregnancy is performed, to check for the presence of congenital anomalies, including congenital heart disease (CHD). Unfortunately, 40% of CHD is still missed. The combined use of ultrasound and electrocardiography might boost detection rates. The electrical heart axis is one of the characteristics which can be deduced from an electrocardiogram (ECG). The aim of this study was to determine reference values for the electrical heart axis in healthy fetuses around 20 weeks of gestation. Material and methods Non-invasive fetal electrocardiography was performed subsequent to the fetal anomaly scan in pregnant women carrying a healthy singleton fetus between 18 and 24 weeks of gestation. Eight adhesive electrodes were applied on the maternal abdomen including one ground and one reference electrode, yielding six channels of bipolar electrophysiological measurements. After removal of interferences, a fetal vectorcardiogram was calculated and then corrected for fetal orientation. The orientation of the electrical heart axis was determined from this normalized fetal vectorcardiogram. Descriptive statistics were used on normalized cartesian coordinates to determine the average electrical heart axis in the frontal plane. Furthermore, 90% prediction intervals (PI) for abnormality were calculated. Results Of the 328 fetal ECGs performed, 281 were included in the analysis. The average electrical heart axis in the frontal plane was determined at 122.7° (90% PI: -25.6°; 270.9°). Discussion The average electrical heart axis of healthy fetuses around mid-gestation is oriented to the right, which is, due to the unique fetal circulation, in line with muscle distribution in the fetal heart.

TRAP1 and cyclophilin D compete at OSCP subunit to regulate enzymatic activity and permeability transition pore opening by F-ATP synthase

Binding of the mitochondrial chaperone TRAP1 to client proteins shapes cell bioenergetic and proteostatic adaptations, but the panel of TRAP1 clients is only partially defined. Here we show that TRAP1 interacts with F-ATP synthase, the protein complex that provides most cellular ATP. TRAP1 competes with the peptidyl-prolyl cis-trans isomerase cyclophilin D (CyPD) for binding to the oligomycin sensitivity-conferring protein (OSCP) subunit of F-ATP synthase, increasing its catalytic activity and counteracting the inhibitory effect of CyPD. Moreover, TRAP1 inhibits opening of the permeability transition pore (PTP) formed by F-ATP synthase and effectively antagonizes the PTP-inducing effect of CyPD, which elicits mitochondrial depolarization and cell death. Consistently, electrophysiological measurements indicate that TRAP1 and CyPD compete in the modulation of channel activity of purified F-ATP synthase, resulting in PTP inhibition and activation, respectively, and outcompeting each other effect on the channel. Moreover, TRAP1 counteracts PTP induction by CyPD, whereas CyPD reverses TRAP1-mediated PTP inhibition. Our data identify TRAP1 as a F-ATP synthase regulator that can influence cell bioenergetics and survival and can be targeted in pathological conditions where these processes are dysregulated, such as cancer.

Listening to speech in noisy scenes: Antithetical contribution of primary and non-primary auditory cortex

Invasive and non-invasive electrophysiological measurements during cocktail-party-like listening indicate that neural activity in human auditory cortex (AC) tracks the envelope of relevant speech. Due to the measurement s limited coverage and/or spatial resolution, however, the distinct contribution of primary and non-primary auditory areas remains unclear. Using 7-Tesla fMRI, here we measured brain responses of participants attending to one speaker, without and with another concurrent speaker. Using voxel-wise modeling, we observed significant speech envelope tracking in bilateral Heschl s gyrus (HG) and middle superior temporal sulcus (mSTS), despite the sluggish fMRI responses and slow temporal sampling. Neural activity was either positively (HG) or negatively (mSTS) correlated to the speech envelope. Spatial pattern analyses indicated that whereas tracking in HG reflected both relevant and (to a lesser extent) non-relevant speech, right mSTS selectively represented the relevant speech signal. These results indicate that primary and non-primary AC antithetically process ongoing speech suggesting a push-pull of acoustic and linguistic information.

That means something to me: the effect of linguistic and emotional experience on the acquisition and processing of novel abstract concepts

This study aimed to investigate the acquisition and representation of novel abstract concepts grounded in linguistic and emotional experience. In five linguistic training sessions, participants learned emotional and neutral abstract concepts and either engaged in explicit mental imagery (n = 32) or lexico-semantic processing (n = 34) with the linguistic material. After training, a high lexical decision and semantic judgment accuracy showed that participants successfully acquired the novel concepts. A feature production task showed that emotional concepts were generally enriched by a surplus of (emotion) features, and neutral concepts by relatively more cognition features. More features led to a higher LDT accuracy but not to faster reactions, which cannot be fully explained by noise due to the online assessment as, descriptively, more features slowed down reactions in participants, who did the imagery task and accelerated them for those, who did the rephrasing task. Our findings support the notion that linguistic and emotional information are crucial for grounding abstract concepts, and that this grounding does not rely on explicit imagery. Future research might combine the linguistic training paradigm with controlled reaction time and electrophysiological measurements to further corroborate the experiential grounding of abstract words.

Mutational analysis to explore long-range allosteric couplings involved in a pentameric channel receptor pre-activation and activation

Pentameric ligand-gated ion channels (pLGICs) mediate chemical signaling through a succession of allosteric transitions that are yet not completely understood as intermediate states remain poorly characterized by structural approaches. In a previous study on the prototypic bacterial proton-gated channel GLIC, we generated several fluorescent sensors of the protein conformation that report a fast transition to a pre-active state, which precedes the slower process of activation with pore opening. Here, we explored the phenotype of a series of allosteric mutations, using paralleled steady-state fluorescence and electrophysiological measurements over a broad pH range. Our data, fitted to a 3-states Monod-Wyman-Changeux (MWC) model, show that mutations at the subunit interface in the extracellular domain (ECD) principally alter pre-activation, while mutations in the lower ECD and in the transmembrane domain principally alter activation. We also show that propofol alters both transitions. Data are discussed in the framework of transition pathways generated by normal mode analysis (iModFit) that suggest collective protein motions concerted with pore opening. It further supports that pre-activation involves major quaternary compaction of the ECD, and suggests that activation involves principally a re-organization of a 'central gating region' involving a contraction of the ECD β-sandwich and the tilt of the channel lining M2 helix.

Preliminary Observations on Skeletal Muscle Adaptation and Plasticity in Homer 2-/- Mice

Homer represents a diversified family of scaffold and transduction proteins made up of several isoforms. Here, we present preliminary observations on skeletal muscle adaptation and plasticity in a transgenic model of Homer 2-/- mouse using a multifaceted approach entailing morphometry, quantitative RT-PCR, confocal immunofluorescence, and electrophysiology. Morphometry shows that Soleus muscle (SOL), at variance with Extensor digitorum longus muscle (EDL) and Flexor digitorum brevis muscle (FDB), displays sizable reduction of fibre cross-sectional area compared to the WT counterparts. In SOL of Homer 2-/- mice, quantitative RT-PCR indicated the upregulation of Atrogin-1 and Muscle ring finger protein 1 (MuRF1) genes, and confocal immunofluorescence showed the decrease of neuromuscular junction (NMJ) Homer content. Electrophysiological measurements of isolated FDB fibres from Homer 2-/- mice detected the exclusive presence of the adult ε-nAChR isoform excluding denervation. As for NMJ morphology, data were not conclusive, and further work is needed to ascertain whether the null Homer 2 phenotype induces any endplate remodelling. Within the context of adaptation and plasticity, the present data show that Homer 2 is a co-regulator of the normotrophic status in a muscle specific fashion.

Directed functional and structural connectivity in a large-scale model for the mouse cortex

Inferring the structural connectivity from electrophysiological measurements is a fundamental challenge in systems neuroscience. Directed functional connectivity measures, such as the Generalized Partial Directed Coherence (GPDC), provide estimates of the causal influence between areas. However, the relation between causality estimates and structural connectivity is still not clear. We analyzed this problem by evaluating the effectiveness of GPDC to estimate the connectivity of a ground-truth, data-constrained computational model of a large-scale network model of the mouse cortex. The model contains 19 cortical areas comprised of spiking neurons, with areas connected by long-range projections with weights obtained from a tract-tracing cortical connectome. We show that GPDC values provide a reasonable estimate of structural connectivity, with an average Pearson correlation over simulations of 0.74. Moreover, even in a typical electrophysiological recording scenario containing five areas, the mean correlation was above 0.6. These results suggest that it may be possible to empirically estimate structural connectivity from functional connectivity even when detailed whole-brain recordings are not achievable.

Az elektródasor visszatekeredésének kimutatása transzimpedanciamátrix (TIM)-vizsgálattal cochlearis implantátumban

Összefoglaló. Bevezetés: Az elmúlt években a cochlearis implantátum a súlyos halláskárosodás vagy a teljes siketség rutinszerű és hatékony kezelési eszközévé vált. Korunk egyik leggyakrabban használt és leghatékonyabb újítása a cochlearis implantációban a perimodiolaris vékony elektródasorok alkalmazása. A cochlea középtengelyét, a modiolust szorosan ölelő atraumatikus elektródasor igen meggyőző eredménnyel bizonyítja népszerűségét, mind az elektrofiziológiai mérések során, mind az akusztikus hallás megőrzése terén nyújtott teljesítményével. Ugyanakkor igen kevés publikáció írja le az elektródasor nem megfelelő helyzetének előfordulási gyakoriságát, pontosabban a visszatekeredését a csúcsi szakaszon. Célkitűzés: Tanulmányunk célja olyan szoftveres technika, a transzimpedancia-mátrix (TIM) beillesztése a rutin intraoperatív elektrofiziológiai mérési metodikák közé, amely képes objektív diagnosztikai lehetőséget biztosítani ahhoz, hogy korán felismerhessük a cochlearis implantátum elektródasorán keletkezett hurkot. Módszer: Hároméves kisgyermek kétoldali cochlearis implantációját követően, posztoperatív röntgenfelvételen a bal oldalon az elektródasor megfelelő pozíciója figyelhető meg, míg a jobb oldalon az intracochlearis elektródasor végének visszatekeredése igazolódott. Képalkotó vizsgálatot követően elektrofiziológiai metódusként TIM-vizsgálatot végeztünk. Az eljárás során a mérőeszköz a kijelölt stimuláló elektródákon 1 V nagyságrendű feszültséget közöl állandó áramerősség mellett a cochlea közel eső struktúrái felé. Mérőelektródák segítségével regisztráljuk a szöveteken mérhető feszültséget, majd transzimpedancia-mátrixszá alakítjuk a mért értékeket. Eredmények: Az elektródasor visszatekeredése, amelyet korábban radiológiai vizsgálattal igazoltunk, az objektív elektrofiziológiai mérések segítségével is jól azonosítható, és a vizsgálatok szoros párhuzamot mutatnak. Következtetés: Az elektródák helyzetének megjelenítésére szolgáló standard radiológiai képalkotási technikák kiegészíthetők, illetve kiválthatók egyszerűen elvégezhető, hatékony, objektív elektrofiziológiai vizsgálatokkal. Intraoperatíven, még a sebzárás előtt kimutatható, ha az elektródasor nem megfelelő helyzetbe került, így csökkenthetjük a radiológiai vizsgálatokkal járó sugárterhelés és annak finanszírozási problémáját. Orv Hetil. 2021; 162(25): 988–996. Summary. Introduction: In recent years, the cochlear implant has become a routine and effective treatment tool for severe hearing loss and total deafness. One of the commonly used and effective innovations of our time in cochlear implantation is the perimodiolar thin electrode array. The atraumatic electrode array, which closely embraces the central axis of the cochlea (modiolus), has served its popularity with very convincing results, with its performance in both electrophysiological measurements and acoustic hearing preservation. However, very few publications describe the frequency of improper positioning of the electrode array, which is known as ‘tip fold-over’. Objective: The aim of our study is to incorporate a software technique, the transimpedance matrix (TIM), into routine intraoperative electrophysiological measurement methodologies to provide a potential objective diagnostic opportunity for early detection of tip fold-over of the electrode array. Method: Following bilateral cochlear implantation of a three-year-old child, postoperative radiography showed the correct position of the electrode array on the left side, while tip fold-over of the intracochlear electrode array was detected on the right side. Following imaging, a TIM study was performed as an electrophysiological method. During the procedure, the measuring device transmits a voltage of the order of 1 V to the nearby structures of the cochlea at a constant current at the designated stimulus electrodes. Measuring electrodes were used to register the voltage measured on the tissues, and then converted into a TIM. Results: Electrode tip fold-over was previously diagnosed by radiological examination, while it can also be diagnosed by objective electrophysiological measurements now, and these two tests correlate well. Conclusion: Standard radiological imaging techniques for electrode positioning can be supplemented or replaced by easy-to-perform, effective objective electrophysiological studies. Tip fold-over can be detected intraoperatively, even before wound closure, if the electrode array is in the wrong position, thus reducing the radiation exposure associated with radiological examinations as well as reducing relevant costs. Orv Hetil. 2021; 162(25): 988–996.

Connectomics of Human Electrophysiology

We present both a scientific overview and conceptual positions concerning the challenges and assets of electrophysiological measurements in the search for the nature and functions of the human connectome. We discuss how the field has been inspired by findings and approaches from functional magnetic resonance imaging (fMRI) and informed by a small number of significant multimodal empirical studies, which show that the canonical networks that are commonplace in fMRI are in fact rooted in electrophysiological processes. This review is also an opportunity to produce a brief, up-to-date critical survey of current data modalities and signal processing methods available for deriving both static and dynamic connectomes using electrophysiological data. We review hurdles that challenge the significance and impact of current electrophysiology connectome research. We then encourage the field to take a leap of faith and embrace the wealth of electrophysiological signals, despite their apparent, disconcerting complexity. Our position is that electrophysiology connectomics is poised to inform testable mechanistic models of information integration in hierarchical brain networks, constructed from observable oscillatory and aperiodic signal components and their polyrhythmic interactions.