Electrophysiological Changes Research Articles

Fibroblast growth factor 13-mediated regulation of medium spiny neuron excitability and cocaine self-administration.

Cocaine use disorder (CUD) is a prevalent neuropsychiatric disorder with few existing treatments. Thus, there is an unmet need for the identification of new pharmacological targets for CUD. Previous studies using environmental enrichment versus isolation paradigms have found that the latter induces increased cocaine self-administration with correlative increases in the excitability of medium spiny neurons (MSN) of the nucleus accumbens shell (NAcSh). Expanding upon these findings, we sought in the present investigation to elucidate molecular determinants of these phenomena. To that end, we first employed a secondary transcriptomic analysis and found that cocaine self-administration differentially regulates mRNA for fibroblast growth factor 13 (FGF13), which codes for a prominent auxiliary protein of the voltage-gated Na+ (Nav) channel, in the NAcSh of environmentally enriched rats (i.e., resilient behavioral phenotype) compared to environmentally isolated rats (susceptible phenotype). Based upon this finding, we used in vivo genetic silencing to study the causal functional and behavioral consequences of knocking down FGF13 in the NAcSh. Functional studies revealed that knockdown of FGF13 in the NAcSh augmented excitability of MSNs by increasing the activity of Nav channels. These electrophysiological changes were concomitant with a decrease in cocaine demand elasticity (i.e., susceptible phenotype). Taken together, these data support FGF13 as being protective against cocaine self-administration, which positions it well as a pharmacological target for CUD.

Oxidized high-density lipoprotein associates with atrial fibrillation

BackgroundAtrial fibrillation (AF) is the most common heart arrhythmia and considered to be a progressive chronic disease associated with increased morbidity and mortality. Recent data suggest a link between inflammation, oxidative stress, and AF, although the underlying mechanisms are not fully understood. Because oxidized lipoproteins cause structural damage and electrophysiologic changes in cardiomyocytes, it is feasible that the transformation of atheroprotective high-density lipoprotein (HDL) into dysfunctional HDL contributes to the development of AF. ObjectiveThe purpose of this study was to determine whether a reduced antioxidant function of HDL is associated with the presence of AF. MethodsIn this multicenter cross-sectional cohort study, we assessed HDL function in sera of 1206 participants. Patients were divided into groups according to the presence of AF (n = 233) or no AF (n = 973). A validated cell-free biochemical assay was used to determine reduced HDL antioxidant function as assessed by increased normalized HDL lipid peroxide content (nHDLox). ResultsParticipants with AF had a 9% higher mean relative nHDLox compared to persons without AF (P = .025). nHDLox was strongly associated with AF in all models of logistic regression, including the analysis adjusted for age, sex, and risk factors for AF (all P ≤.01). ConclusionReduced antioxidant HDL function is associated with the presence of AF, which supports growing evidence that impaired lipoprotein function is linked to electrophysiological changes in cardiomyocytes. nHDLox is one of several contributors to the initiation and perpetuation of AF.

Determinants of electrical propagation and propagation block in Arrhythmogenic Cardiomyopathy

Gap junction and ion channel remodeling occur early in Arrhythmogenic Cardiomyopathy (ACM), but their pathogenic consequences have not been elucidated. Here, we identified the arrhythmogenic substrate, consisting of propagation slowing and conduction block, in ACM models expressing two different desmosomal gene variants. Neonatal rat ventricular myocytes were transduced to express variants in genes encoding desmosomal proteins plakoglobin or plakophilin-2. Studies were performed in engineered cells and anisotropic tissues to quantify changes in conduction velocity, formation of unidirectional propagation, cell–cell electrical coupling, and ion currents. Conduction velocity decreased by 71% and 63% in the two ACM models. SB216763, an inhibitor of glycogen synthase kinase-3 beta, restored conduction velocity to near normal levels. Compared to control, both ACM models showed greater propensity for unidirectional conduction block, which increased further at greater stimulation frequencies. Cell–cell electrical conductance measured in cell pairs was reduced by 86% and 87% in the two ACM models. Computer modeling showed close correspondence between simulated and experimentally determined changes in conduction velocity. The simulation identified that reduced cell–cell electrical coupling was the dominant factor leading to slow conduction, while the combination of reduced cell–cell electrical coupling, reduced sodium current and inward rectifier potassium current explained the development of unidirectional block. Expression of two different ACM variants markedly reduced cell–cell electrical coupling and conduction velocity, and greatly increased the likelihood of developing unidirectional block – both key features of arrhythmogenesis. This study provides the first quantitative analysis of cellular electrophysiological changes leading to the substrate of reentrant arrhythmias in early stage ACM.

Hippocampal interneuronal dysfunction and hyperexcitability in a porcine model of concussion

Cognitive impairment is a common symptom following mild traumatic brain injury (mTBI or concussion) and can persist for years in some individuals. Hippocampal slice preparations following closed-head, rotational acceleration injury in swine have previously demonstrated reduced axonal function and hippocampal circuitry disruption. However, electrophysiological changes in hippocampal neurons and their subtypes in a large animal mTBI model have not been examined. Using in vivo electrophysiology techniques, we examined laminar oscillatory field potentials and single unit activity in the hippocampal network 7 days post-injury in anesthetized minipigs. Concussion altered the electrophysiological properties of pyramidal cells and interneurons differently in area CA1. While the firing rate, spike width and amplitude of CA1 interneurons were significantly decreased post-mTBI, these parameters were unchanged in CA1 pyramidal neurons. In addition, CA1 pyramidal neurons in TBI animals were less entrained to hippocampal gamma (40–80 Hz) oscillations. Stimulation of the Schaffer collaterals also revealed hyperexcitability across the CA1 lamina post-mTBI. Computational simulations suggest that reported changes in interneuronal physiology may be due to alterations in voltage-gated sodium channels. These data demonstrate that a single concussion can lead to significant neuronal and circuit level changes in the hippocampus, which may contribute to cognitive dysfunction following mTBI.

Characterization of atrial cardiomyopathy subtypes - A cellular electrophysiological comparison and evaluation of appropriate treatment options

Abstract Background Atrial fibrillation occurs in the context of atrial remodeling processes which are the result of an underlying atrial cardiomyopathy (AC). Insufficient understanding of the pathophysiological mechanisms behind AC contributes significantly to the fact that current clinical strategies for the treatment of atrial fibrillation are often ineffective. A systematic investigation of these cellular remodeling processes in the context of the various cardiac diseases underlying AC is still missing. Purpose The aim of this study was to characterize different subtypes of AC associated with common cardiac disease entities by systematic cellular electrophysiological characterization of the atria in combination with molecular and structural investigations. Methods For a comprehensive analysis of the molecular changes associated with AC, we characterized several mouse models of common heart diseases, including models for dilated cardiomyopathy (DCM), HFpEF, mitral regurgitation and immune checkpoint inhibitor (ICI-)mediated myocarditis. Patch clamp experiments were performed on isolated atrial cardiomyocytes to study atrial action potentials (aAP) and different ion currents contributing to the aAP. The cellular electrophysiological parameters of the different models were correlated to clinical parameters (ecg, echocardiography of the atria) of the mouse models and with data from RNA sequencing of the mice’ atria. Results Patch clamp measurements performed on isolated left and right atrial cardiomyocytes revealed distinct differences among the examined models. In all pathophysiological models, the aAP was significantly shorter than in the corresponding wild type mice. The different ion current components we measured various changes in potassium, sodium and calcium currents. The repolarizing TASK-1 potassium current was significantly increased in all models. The DCM model caused by an R636Q mutation in the RBM20 gene showed the most severe changes in cellular electrophysiology. Considering the detected atrial changes, we investigated the effects of SGLTi on atrial cardiomyocytes of the different models. When elevated concentrations of dapa-, empa- and sotagliflozin were administrated on atrial cardiomyocytes, a class-I-antiarrhythmic effect with reduced aAP inducibility and changes in the aAP duration could be observed. Conclusion Characterization of murine models of cardiac disease with respect to classification of AC subtypes revealed various electrical remodeling processes at the level of ion currents involved in aAP formation. A potent inductor of atrial proarrhythmogenity in the AC subtypes was an aAP shortening caused by an increase in repolarizing potassium currents, mediated especially by TASK-1. The most severe electrical remodeling in atria cardiomyocytes was observed in the RBM20-mutant model (DCM). SGLTi exhibit anti-arrhythmic effects in different murine disease models and may provide future treatment options for patients with AC.

Abstract 11632: Altered Autonomic Balance Linked to Arrhythmogenicity in Chronic Myocardial Infarction Ovine Model

Background: Increased sympathetic drive resulting in decreased heart rate variability (HRV), has been linked to cardiovascular diseases such as heart failure and myocardial infarction (MI). Dynamic electrophysiological changes due to acute ischemia and chronic MI are known to be pro-arrhythmic. Objective: Evaluate the changes in autonomic tone resulting from substrate remodeling during the development of chronic MI in an in-vivo ovine model. Methods: ECG recordings were collected at baseline, post occlusion and 6 weeks post MI, in young adult sheep (n=16). Time domain, frequency domain and non-linear measures of HRV were evaluated from 10 minutes of ECG data at the 3 time points. RR interval, heart rate, SDRR (standard deviation of the RR intervals), RMSSD (root mean square of successive differences between normal heartbeats), QTc interval, pNN 50 , LF/HF ratio and SD1/SD2 ratio were calculated and compared between baseline, post acute coronary artery occlusion and after 6 weeks of chronic MI. 24-hour telemetry was also performed in an ambulatory animal for 6 weeks to monitor the progression of alterations in the T-wave morphology or duration, i.e. T-wave alternans, a known marker of ventricular tachyarrhythmias, with chronic MI. Results: Chronic MI led to significantly decreased RR interval (Fig.1A) and increased heart rate (Fig.1B), along with a significant prolongation of the QTc interval (Fig.1C). Significant rise was also observed in the SDRR (Fig1D) and LF/HF ratio (Fig1E) indicating a shift towards increased sympathetic tone and reduced parasympathetic drive. In addition to the autonomic changes, a significant rise in T-wave alternans burden (Fig1F) and localized action potential alternans inducibility was observed with progression of MI indicating increased arrhythmogenicity. Conclusion: Skewed autonomic balance is evident in chronic MI and may be closely linked to increased arrhythmogenicity.

Water Extract of Capsella bursa-pastoris Mitigates Doxorubicin-Induced Cardiotoxicity by Upregulating Antioxidant Enzymes

Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of Capsella bursa-pastoris (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death. Superoxide dismutase (SOD) levels, reactive oxygen species (ROS) production, and oxygen consumption rate were measured in H9c2 cells. C57BL/6 mice were treated with DOX and CBW to assess their impact on various cardiac parameters. Human-induced pluripotent stem-cell-derived cardiomyocytes were also used to investigate DOX-induced electrophysiological changes and the potential ameliorative effects of CBW. UPLC-TQ/MS analysis identified seven flavonoids in CBW, with luteolin-7-O-glucoside and isoorientin as the major compounds. CBW inhibited DOX-induced death of H9c2 rat cardiomyocytes but did not affect DOX-induced death of MDA-MB-231 human breast cancer cells. CBW increased SOD levels in a dose-dependent manner, reducing ROS production and increasing the oxygen consumption rate in H9c2 cells. The heart rate, RR interval, QT, and ST prolongation remarkably recovered in C57BL/6 mice treated with the combination of DOX and CBW compared to those in mice treated with DOX alone. Administration of CBW with DOX effectively alleviated collagen accumulation, cell death in mouse heart tissues, and reduced the levels of creatinine kinase (CK) and lactate dehydrogenase (LDH) in serum. Furthermore, DOX-induced pathological electrophysiological features in human-induced pluripotent stem-cell-derived cardiomyocytes were ameliorated by CBW. CBW may prevent DICT by stabilizing SOD and scavenging ROS. The presence of flavonoids, particularly luteolin-7-O-glucoside and isoorientin, in CBW may contribute to its protective effects. These results suggest the potential of CBW as a traditional therapeutic option to mitigate DOX-induced cardiotoxicity.

Underlying mechanism of atrial fibrillation–associated Nppa-I137T mutation and cardiac effect of potential drug therapy

BackgroundMore than a hundred genetic loci have been associated with atrial fibrillation (AF). But the exact mechanism remains unclear and the treatment needs to be improved. ObjectiveThis study aimed to investigate the mechanism and potential treatment of NPPA mutation–associated AF. MethodsNppa knock-in (KI, p.I137T) rats were generated, and cardiac function was evaluated. Blood pressure was recorded using a tail-cuff system. The expression levels were measured using real-time polymerase chain reaction, enzyme-linked immunosorbent assay or Western blot analysis, and RNA-sequence analysis. Programmed electrical stimulation, patch clamp, and multielectrode array were used to record the electrophysical characteristics. ResultsMutant rats displayed downregulated expression of atrial natriuretic peptide but elevated blood pressure and enlarged left atrial end-diastolic diameter. Further, gene topology analysis suggested that the majority of differently expressed genes in Nppa KI rats were related to inflammation, electrical remodeling, and structural remodeling. The expression levels of C-C chemokine ligand 5 and galectin-3 involved in remodeling were higher, while there were declined levels of Nav1.5, Cav1.2, and connexin 40. AF was more easily induced in KI rats. Electrical remodeling included abbreviated action potentials, effective refractory period, increased late sodium current, and reduced calcium current, giving rise to conduction abnormalities. These electrophysiological changes could be reversed by the late sodium current blocker ranolazine and the Nav1.8 blocker A-803467. ConclusionOur findings suggest that structural remodeling related to inflammation and fibrosis and electrical remodeling involved in late sodium current underly the major effects of the Nppa (p.I137T) variant to induce AF, which can be attenuated by the late sodium current blocker and Nav1.8 blocker.

36 Impact of Neuropsychological Performance and Anxiety on Meditation in Drug Resistant Epilepsy (DRE) Patients Implanted with a Responsive Neurostimulation (RNS) Device

Objective:Responsive neurostimulation (RNS) is a surgical intervention to reduce the frequency of seizures as an adjunctive therapy for patients with drug-resistant epilepsy (DRE). Presurgical neuropsychological evaluations capture symptoms of anxiety and depression, which occur in higher rates within the epilepsy population than in the general population; however, the effects of mood are commonly overlooked or underappreciated in the conceptualization of cognitive functioning and overall quality of life. Previous studies have shown the effects of attentional control and executive functioning on engagement in meditative states. The present study examines pre and post-meditation self-reported anxiety symptoms and the electrophysiological changes captured intracranially during meditation sessions in patients implanted with an RNS device. This study seeks to utilize presurgical neuropsychological evaluations to explore relationships between cognitive profiles and meditative state changes, and reductions in anxiety.Participants and Methods:This study presents a series of 10 patients who underwent RNS device implantation for the treatment of DRE at Mount Sinai Hospital. All patients had at least one contact in the basolateral amygdala. Prior to surgical implantation of the RNS device, all patients completed a comprehensive neuropsychological evaluation based on the NIH Common Data Elements Battery for Epilepsy Patients. Patients in this study completed a 17-and 22-minute meditation protocol based on loving-kindness and Focal Awareness (FA) meditation. Control points and mind-wandering phases were utilized to distinguish the meditative portion of the study during intracranial recordings. All patients completed a pre- and post-meditation questionnaire adapted from the PROMIS Anxiety Short Form as well as self-ratings on meditation depth and satisfaction.Results:Presurgical neuropsychological evaluation of patients showed elevated levels of anxiety on the BAI (M = 18.14, SD = 12.03) and depression on the BDI-II (M = 15.57, SD = 6.92). Neuropsychological findings localized to frontal or frontotemporal deficits in 80% of the patients were captured in this study. Regarding lateralization, 50% of patients presented with bilateral weakness on neuropsychological evaluation, with the rest showing unilateral profiles. A negative correlation was observed between patient responses on pre-meditation anxiety measures and self-reported depth of engagement in meditation, r = -0.65, p = .043. When all meditation sessions were evaluated, patients displayed a reduction in anxiety levels pre- and post- meditation, t = 2.3, p = .03.Conclusions:Present findings suggest a reduction in anxiety symptoms following completion of a meditation paradigm. Additionally, a relationship between anxiety and depth of engagement in meditation was identified. During each meditation session, electrocorticography data was collected and analyzed. Given the high comorbidities of anxiety and depression as well as cognitive symptoms common for individuals with epilepsy, a systems-based approach may enhance conceptualization of neuropsychological and neuropsychiatric evaluations, which may have a significant clinical impact. Evaluation of neuropsychological profiles, meditation effects, and anxiety in this population may support cross-discipline understanding of cognitive and psychiatric profiles to better inform treatment recommendations.

Retracted: Neurotransmitters and Electrophysiological Changes Might Work as Biomarkers for Diagnosing Affective Disorders.

[This retracts the article DOI: 10.1155/2021/9116502.].

EEG-Based Functional Connectivity Analysis for Cognitive Impairment Classification

Understanding how mild cognitive impairment affects global neural networks may explain changes in brain electrophysiology. Using graph theory and the visual oddball paradigm, we evaluated the functional connectivity of neuronal networks in brain lobes. The study involved 30 participants: 14 with mild cognitive impairment (MCI) and 16 healthy control (HC) participants. We conducted an examination using the visual oddball paradigm, focusing on electroencephalography signals with targeted stimuli. Our analysis employed functional connectivity utilizing the change point detection method. Additionally, we implemented training for linear discriminant analysis, K-nearest neighbor, and decision tree techniques to classify brain activity, distinguishing between subjects with mild cognitive impairment and those in the healthy control group. Our results demonstrate the efficacy of combining functional connectivity measurements derived from electroencephalography with machine learning for cognitive impairment classification. This research opens avenues for further exploration, including the potential for real-time detection of cognitive decline in complex real-world scenarios.

Analysis of the characteristics and clinical significance of pelvic floor electrophysiology and imaging changes in female patients with MFPP

ObjectiveChronic Pelvic Pain (CPP) is a very common disease. Studies have found that some female patients with CPP have a myofascial trigger point for pain, which has classified as myofascial pelvic pain (MFPP). This study intends to compare the changes of pelvic floor electrophysiology and imaging between female patients with MFPP and normal women by measuring pelvic floor muscle potential, tension and two-dimensional and three-dimensional ultrasound, and then to explore the characteristics and significance of the changes. MethodsA total of 49 MFPP patients were randomly selected as the study group and 41 healthy women were randomly selected as the control group. Vaginal muscle potential was detected by pelvic floor muscle potential tester. The electronic tensioner was used to measure the muscle tension and the pelvic floor muscle contraction force of 5o and 10o, respectively. The parameters of the two groups were detected by transperineal 2D ultrasound and transvaginal 3D ultrasound respectively. Results1. The resting muscle potential and maximum muscle potential of the study group were higher than those of the control group. 2. The static tension, dynamic tension and contractile force of pelvic floor muscle in the study group were higher than those in the control group when the tensioner was opened for 5o. 3. In resting state, BND, BSD and anterior-to-posterior diameter of genital tract hiatus in the study group were smaller than those in the control group. The anal Angle in Valsalva state was greater in study group than in control group. 4. At rest, the hiatus area, anterior-posterior diameter, transverse diameter and defect score of the levator anal muscle in the study group were smaller than those in the control group. ConclusionMFPP presents a state of continuous spasm and loss of coordination of pelvic floor muscle fascia.

Provocative changes in nerve conductions: Fact or fiction?

At times electrodiagnostic medical consultants (EMCs) are asked to perform studies in both a neutral position, and then again after the patient is in a provocative position that exacerbates symptoms, to assess for measurable electrophysiologic changes. While this approach might seem initially appealing, particularly when standard studies are not effective at diagnosis, empiric studies in several conditions have been unimpressive. Studies in median neuropathy at the wrist, thoracic outlet syndrome, piriformis syndrome, and radial tunnel syndrome have failed to demonstrate reproducible changes in nerve conduction studies in positions that exacerbate symptoms. Furthermore, there is lack of a plausible pathophysiologic mechanism for producing both measurable and rapidly reversible electrophysiologic changes after just a few minutes, or less, of compression. Axon loss and demyelination would not be rapidly reversible, and positional changes of 2 min or less (the durations generally studied) would be insufficient to produce measurable nerve ischemia. Last, we have gained a greater appreciation for how much nerves move within limbs with changes in joint position; this movement can lead to misleading changes in nerve conduction studies. It is thus appropriate to conclude that testing nerve conduction in provocative or symptomatic positions adds no value to electrodiagnostic testing.

Synaptic remodeling follows upper motor neuron hyperexcitability in a rodent model of TDP-43.

Amyotrophic Lateral Sclerosis (ALS) is an incurable disease characterized by relentlessly progressive degeneration of the corticomotor system. Cortical hyperexcitability has been identified as an early pre-symptomatic biomarker of ALS. This suggests that hyperexcitability occurs upstream in the ALS pathological cascade and may even be part of the mechanism that drives development of symptoms or loss of motor neurons in the spinal cord. However, many studies also indicate a loss to the synaptic machinery that mediates synaptic input which raises the question of which is the driver of disease, and which is a homeostatic response. Herein, we used an inducible mouse model of TDP-43 mediated ALS that permits for the construction of detailed phenotypic timelines. Our work comprehensively describes the relationship between intrinsic hyperexcitability and altered synaptic input onto motor cortical layer 5 pyramidal neurons over time. As a result, we have constructed the most complete timeline of electrophysiological changes following induction of TDP-43 dysfunction in the motor cortex. We report that intrinsic hyperexcitability of layer 5 pyramidal neurons precedes changes to excitatory synaptic connections, which manifest as an overall loss of inputs onto layer 5 pyramidal neurons. This finding highlights the importance of hyperexcitability as a primary mechanism of ALS and re-contextualizes synaptic changes as possibly representing secondary adaptive responses. Recognition of the relationship between intrinsic hyperexcitability and reduced excitatory synaptic input has important implications for the development of useful therapies against ALS. Novel strategies will need to be developed that target neuronal output by managing excitability against synapses separately.

Long-term spaceflight composite stress induces depressive behaviors in model rats through disrupting hippocampus synaptic plasticity.

Long-term spaceflight composite stress (LSCS) can cause adverse effects on human systems, including the central nervous system, which could trigger anxiety and depression. This study aimed to identify changes in hippocampus synaptic plasticity under LSCS. The present study simulated the real long-term space station environment by conducting a 42-day experiment that involved simulating microgravity, isolation, noise, circadian rhythm disruptions, and low pressure. The mood and behavior of the rats were assessed by behavior test. Transmission electron microscopy and patch-clamp were used to detect the changes in synapse morphology and electrophysiology, and finally, the expression of NMDA receptor channel proteins was detected by western blotting. The results showed that significant weight loss, anxiety, and depressive behaviors in rats were observed after being exposed to LSCS environment for 42 days. The synaptic structure was severely damaged, manifested as an obvious decrease in postsynaptic density thickness and synaptic interface curvature (p < 0.05; p < 0.05, respectively). Meanwhile, LTP was significantly impaired (p < 0.0001), and currents in the NMDAR channel were also significantly reduced (p < 0.0001). Further analysis found that LSCS decreased the expression of two key subtype proteins on this channel. These results suggested that LSCS-induced depressive behaviors by impairing synaptic plasticity in rat hippocampus.

Six-Lead Electrocardiography Enables Identification of Rhythm and Conduction Anomalies of Patients in the Telemedicine-Based, Hospital-at-Home Setting: A Prospective Validation Study.

The hospital-at-home (HAH) model is a viable alternative for conventional in-hospital stays worldwide. Serum electrolyte abnormalities are common in acute patients, especially in those with many comorbidities. Pathologic changes in cardiac electrophysiology pose a potential risk during HAH stays. Periodical electrocardiogram (ECG) tracing is therefore advised, but few studies have evaluated the accuracy and efficiency of compact, self-activated ECG devices in HAH settings. This study aimed to evaluate the reliability of such a device in comparison with a standard 12-lead ECG. We prospectively recruited consecutive patients admitted to the Sheba Beyond Virtual Hospital, in the HAH department, during a 3-month duration. Each patient underwent a 12-lead ECG recording using the legacy device and a consecutive recording by a compact six-lead device. Baseline patient characteristics during hospitalization were collected. The level of agreement between devices was measured by Cohen's kappa coefficient for inter-rater reliability (Ϗ). Fifty patients were included in the study (median age 80 years, IQR 14). In total, 26 (52%) had electrolyte disturbances. Abnormal D-dimer values were observed in 33 (66%) patients, and 12 (24%) patients had elevated troponin values. We found a level of 94.5% raw agreement between devices with regards to nine of the options included in the automatic read-out of the legacy device. The calculated Ϗ was 0.72, classified as a substantial consensus. The rate of raw consensus regarding the ECG intervals' measurement (PR, RR, and QT) was 78.5%, and the calculated Ϗ was 0.42, corresponding to a moderate level of agreement. This is the first report to our knowledge regarding the feasibility of using a compact, six-lead ECG device in the setting of an HAH to be safe and bearing satisfying agreement level with a legacy, 12-lead ECG device, enabling quick, accessible arrythmia detection in this setting. Our findings bear a promise to the future development of telemedicine-based hospital-at-home methodology.

Longitudinal change in mismatch negativity (MMN) but not in gamma-band auditory steady-state response (ASSR) is associated with psychological difficulties in adolescence.

Adolescence is a critical period for psychological difficulties. Auditory mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are representative electrophysiological indices that mature during adolescence. However, the longitudinal association between MMN/ASSR and psychological difficulties among adolescents remains unclear. We measured MMN amplitude for duration and frequency changes and ASSR twice in a subsample (n = 67, mean age 13.4 and 16.1years, respectively) from a large-scale population-based cohort. No significant longitudinal changes were observed in any of the electroencephalography indices. Changes in SDQ-TD were significantly associated with changes in duration MMN, but not frequency MMN and ASSR. Furthermore, the subgroup with higher SDQ-TD at follow-up showed a significant duration MMN decrease over time, whereas the subgroup with lower SDQ-TD did not. The results of our population neuroscience study suggest that insufficient changes in electroencephalography indices may have been because of the short follow-up period or non-monotonic change during adolescence, and indicated that the longitudinal association with psychological difficulties was specific to the duration MMN. These findings provide new insights that electrophysiological change may underlie the development of psychosocial difficulties emerging in adolescence.

Multifunctional fibers enable modulation of cortical and deep brain activity during cognitive behavior in macaques.

Recording and modulating neural activity in vivo enables investigations of the neurophysiology underlying behavior and disease. However, there is a dearth of translational tools for simultaneous recording and localized receptor-specific modulation. We address this limitation by translating multifunctional fiber neurotechnology previously only available for rodent studies to enable cortical and subcortical neural recording and modulation in macaques. We record single-neuron and broader oscillatory activity during intracranial GABA infusions in the premotor cortex and putamen. By applying state-space models to characterize changes in electrophysiology, we uncover that neural activity evoked by a working memory task is reshaped by even a modest local inhibition. The recordings provide detailed insight into the electrophysiological effect of neurotransmitter receptor modulation in both cortical and subcortical structures in an awake macaque. Our results demonstrate a first-time application of multifunctional fibers for causal studies of neuronal activity in behaving nonhuman primates and pave the way for clinical translation of fiber-based neurotechnology.

NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and its prevalence increases with age. The irregular and rapid contraction of the atria can lead to ineffective blood pumping, local blood stasis, blood clots, ischemic stroke, and heart failure. NADPH oxidases (NOX) and mitochondria are the main sources of reactive oxygen species in the heart, and dysregulated activation of NOX and mitochondrial dysfunction are associated with AF pathogenesis. NOX- and mitochondria-derived oxidative stress contribute to the onset of paroxysmal AF by inducing electrophysiological changes in atrial myocytes and structural remodeling in the atria. Because high atrial activity causes cardiac myocytes to expend extremely high energy to maintain excitation-contraction coupling during persistent AF, mitochondria, the primary energy source, undergo metabolic stress, affecting their morphology, Ca2+ handling, and ATP generation. In this review, we discuss the role of oxidative stress in activating AF-triggered activities, regulating intracellular Ca2+ handling, and functional and anatomical reentry mechanisms, all of which are associated with AF initiation, perpetuation, and progression. Changes in the extracellular matrix, inflammation, ion channel expression and function, myofibril structure, and mitochondrial function occur during the early transitional stages of AF, opening a window of opportunity to target NOX and mitochondria-derived oxidative stress using isoform-specific NOX inhibitors and mitochondrial ROS scavengers, as well as drugs that improve mitochondrial dynamics and metabolism to treat persistent AF and its transition to permanent AF.

Short- and Long-Term High-Fat Diet Exposure Differentially Alters Phasic and Tonic GABAergic Signaling onto Lateral Orbitofrontal Pyramidal Neurons.

The chronic consumption of caloric dense high-fat foods is a major contributor to increased body weight, obesity, and other chronic health conditions. The orbitofrontal cortex (OFC) is critical in guiding decisions about food intake and is altered with diet-induced obesity. Obese rodents have altered morphologic and synaptic electrophysiological properties in the lateral orbitofrontal cortex (lOFC). Yet the time course by which exposure to a high-fat diet (HFD) induces these changes is poorly understood. Here, male mice are exposed to either short-term (7 d) or long-term (90 d) HFD. Long-term HFD exposure increases body weight, and glucose signaling compared with short-term HFD or a standard control diet (SCD). Both short and long-term HFD exposure increased the excitability of lOFC pyramidal neurons. However, phasic and tonic GABAergic signaling was differentially altered depending on HFD exposure length, such that tonic GABAergic signaling was decreased with early exposure to the HFD and phasic signaling was changed with long-term diet exposure. Furthermore, alterations in the short-term diet exposure were transient, as removal of the diet restored electrophysiological characteristics similar to mice fed SCD, whereas long-term HFD electrophysiological changes were persistent and remained after HFD removal. Finally, we demonstrate that changes in reward devaluation occur early with diet exposure. Together, these results suggest that the duration of HFD exposure differentially alters lOFC function and provides mechanistic insights into the susceptibility of the OFC to impairments in outcome devaluation.SIGNIFICANCE STATEMENT This study provides mechanistic insight on the impact of short-term and long-term high-fat diet (HFD) exposure on GABAergic function in the lateral orbitofrontal cortex (lOFC), a region known to guide decision-making. We find short-term HFD exposure induces transient changes in firing and tonic GABA action on lOFC pyramidal neurons, whereas long-term HFD induces obesity and has lasting changes on firing, tonic GABA and inhibitory synaptic transmission onto lOFC neurons. Given that GABAergic signaling in the lOFC can influence decision-making around food, these results have important implications in present society as palatable energy dense foods are abundantly available.