Electrophysiological Mechanisms Research Articles

Mechanistic Insights into Melatonin’s Antiarrhythmic Effects in Acute Ischemia-Reperfusion-Injured Rabbit Hearts Undergoing Therapeutic Hypothermia

The electrophysiological mechanisms underlying melatonin’s actions and the electrophysiological consequences of superimposed therapeutic hypothermia (TH) in preventing cardiac ischemia-reperfusion (IR) injury-induced arrhythmias remain largely unknown. This study aimed to unveil these issues using acute IR-injured hearts. Rabbits were divided into heart failure (HF), HF+melatonin, control, and control+melatonin groups. HF was induced by rapid right ventricular pacing. Melatonin was administered orally (10 mg/kg/day) for four weeks, and IR was created by 60-min coronary artery ligation and 30-min reperfusion. The hearts were then excised and Langendorff-perfused for optical mapping studies at normothermia, followed by TH. Melatonin significantly reduced ventricular fibrillation (VF) maintenance. In failing hearts, melatonin reduced the spatially discordant alternans (SDA) inducibility mainly by modulating intracellular Ca2+ dynamics via upregulation of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) and calsequestrin 2 and attenuating the downregulation of phosphorylated phospholamban protein expression. In control hearts, melatonin improved conduction slowing and reduced dispersion of action potential duration (APDdispersion) by upregulating phosphorylated connexin 43, attenuating the downregulation of SERCA2a and phosphorylated phospholamban and attenuating the upregulation of phosphorylated Ca2+/calmodulin-dependent protein kinase II. TH significantly retarded intracellular Ca2+ decay slowed conduction, and increased APDdispersion, thereby facilitating SDA induction, which counteracted the beneficial effects of melatonin in reducing VF maintenance.

The Role of RyR2 Mutations in Congenital Heart Diseases: Insights Into Cardiac Electrophysiological Mechanisms.

Ryanodine receptor 2 (RyR2) protein, a calcium ion release channel in the sarcoplasmic reticulum (SR) of myocardial cells, plays a crucial role in regulating cardiac systolic and diastolic functions. Mutations in RyR2 and its dysfunction are implicated in various congenital heart diseases (CHDs). Studies have shown that mutations in the RYR2 gene, which encodes the RyR2 protein, are linked to several cardiac arrhythmias, including catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), calcium release deficiency syndrome (CRDS), and atrial fibrillation (AF). Additionally, RyR2 mutations have been associated with multiple genetic cardiomyopathies, such as left ventricular non-compaction cardiomyopathy (LVNC), arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Through various cell and animal models, researchers have developed mutant RyR2 models demonstrated that these mutations often lead to calcium dysregulation, typically resulting in either a gain or loss of function. This comprehensive review delves into the current understanding of RyR2 mutations and their impact on cardiac electrophysiology, focusing on the molecular mechanisms linking these mutations to arrhythmias and cardiomyopathies-an essential step in advancing diagnostic and therapeutic strategies.

Aperiodic and oscillatory systems underpinning human domain-general cognition

Domain-general cognitive systems are essential for adaptive human behaviour, supporting various cognitive tasks through flexible neural mechanisms. While fMRI studies link frontoparietal network activation to increasing demands across various tasks, the electrophysiological mechanisms underlying this domain-general response to demand remain unclear. Here, we used MEG/EEG, and separated the aperiodic and oscillatory components of the signals to examine their roles in domain-general cognition across three cognitive tasks using multivariate analysis. We found that both aperiodic (broadband power, slope, and intercept) and oscillatory (theta, alpha, and beta power) components coded task demand and content across all subtasks. Aperiodic broadband power in particular strongly coded task demand, in a manner that generalised across all subtasks. Source estimation suggested that increasing cognitive demand decreased aperiodic broadband power across the brain, with the strongest modulations overlapping with the frontoparietal network. In contrast, oscillatory activity showed more localised patterns of modulation, primarily in frontal or occipital regions. These results provide insights into the electrophysiological underpinnings of human domain-general cognition, highlighting the critical role of aperiodic broadband power.

Assessment of electrophysiological mechanisms of ventricular ectopia in arrhythmogenic right ventricular dysplasia

Relevance of the problem. Arrhythmogenic right ventricular dysplasia (ARVD) is one of the significant causes of sudden cardiac death (SCD) among young people. ARVD is characterized by premature ventricular ectopic contractions (PVCs) from the right ventricular outflow tract (RVOT), which may occur before morphological changes appear and, in these cases, it is necessary to assess the risk of developing SCD based on an analysis of the electrophysiological mechanism of the development of PVCs. Purpose of the study. To evaluate the electrophysiological mechanisms of PVCs in patients with ARVD according to stress tests. Material and methods. We examined 13 patients with confirmed ARVD on MRI, including 9 men and 4 women, aged from 26 to 63 years (42.9±11.0). All patients underwent the following studies: standard electrocardiography (ECG), 24-hour ECG monitoring, echocardiography, cardiac MRI, treadmill stress test. During the stress test, at each load level, ventricular ectopy was analyzed (morphology, number of ventricular ectopic complexes), and the dependence of corrected QTc on heart rate was assessed. Results. According to the data obtained, the patients were divided into two groups depending on the response of PVCs to physical activity. The first group – patients in whom the number of PVCs increased during physical activity – stress-induced ventricular ectopy – 10 people (77%). The second group – patients in whom the number of PVCs decreased, or they disappeared at the peak of the load – stress-inhibited ventricular ectopy – 3 people (23%). All patients had a normal reaction of the QT interval to physical activity – its shortening in response to an increase in heart rate. Conclusions. ARVD is characterized by ventricular ectopia from the right ventricle outflow tract or bifocal ectopia from the right ventricle outflow tract and the right ventricle apex. The electrophysiological mechanisms of ventricular ectopia in ARVD are different: the mechanism of trigger activity and increased automaticity.

Slow oscillation-spindle coupling predicts sequence-based language learning.

Sentence comprehension involves the rapid decoding of both semantic and grammatical information, a process fundamental to communication. As with other complex cognitive processes, language comprehension relies, in part, on long-term memory. However, the electrophysiological mechanisms underpinning the initial encoding and generalisation of higher-order linguistic knowledge remain elusive, particularly from a sleep-based consolidation perspective. One candidate mechanism that may support the consolidation of higher-order language is the temporal coordination of slow oscillations (SO) and sleep spindles during non-rapid eye movement sleep (NREM). To examine this hypothesis, we analysed electroencephalographic (EEG) data recorded from 35 participants (Mage = 25.4, SD = 7.10; 16 males) during an artificial language learning task, contrasting performance between individuals who were given an 8hr nocturnal sleep period or an equivalent period of wake. We found that sleep relative to wake was associated with superior performance for rules that followed a sequence-based word order. Post-sleep sequence-based word order processing was further associated with less task-related theta desynchronisation, an electrophysiological signature of successful memory consolidation, as well as cognitive control and working memory. Frontal NREM SO-spindle coupling was also positively associated with behavioural sensitivity to sequence-based word order rules, as well as with task-related theta power. As such, theta activity during retrieval of previously learned information correlates with SO-spindle coupling, thus linking neural activity in the sleeping and waking brain. Taken together, this study presents converging behavioral and neurophysiological evidence for a role of NREM SO-spindle coupling and task-related theta activity as signatures of successful memory consolidation and retrieval in the context of higher-order language learning.Significance statement The endogenous temporal coordination of neural oscillations supports information processing during both wake and sleep states. Here we demonstrate that slow oscillation-spindle coupling during non-rapid eye movement sleep predicts the consolidation of complex grammatical rules and modulates task-related oscillatory dynamics previously implicated in sentence processing. We show that increases in theta power predict enhanced sensitivity to grammatical violations after a period of sleep and strong slow oscillation-spindle coupling modulates subsequent task-related theta activity to influence behaviour. Our findings reveal a complex interaction between both wake- and sleep-related oscillatory dynamics during the early stages of language learning beyond the single word level.

T-Type Voltage-Gated Calcium Channels: Potential Regulators of Smooth Muscle Contractility.

Emerging evidence has indicated a possible link between attenuation of contractility in aortic smooth muscle cells and pathogenesis of aortic dissection, as revealed through comprehensive, multi-omic analyses of familial thoracic aortic aneurysm and dissection models. While L-type voltage-gated calcium channels have been extensively investigated for their roles in smooth muscle contraction, more recent investigations have suggested that downregulation of T-type voltage-gated calcium channels, rather than their L-type counterparts, may be more closely associated with impaired contractility observed in vascular smooth muscle cells. This review provides a detailed examination of T-type voltage-gated calcium channels, highlighting their structure, electrophysiology, biophysics, expression patterns, functional roles, and potential mechanisms through which their downregulation may contribute to reduced contractile function. Furthermore, the application of multi-omic approaches in investigating calcium channels is discussed.

Effects and mechanisms of dexmedetomidine preconditioning on isoproterenol-induced ventricular arrhythmias

Dexmedetomidine (DEX) is commonly used in clinical practice because of its sedative, analgesic, antisympathetic, hemodynamic stabilization and antianxiety effects. Previous clinical studies have demonstrated that DEX plays a role in both the prevention and treatment of perioperative arrhythmias. However, the precise mechanisms underlying the effects of DEX remain unclear. Furthermore, few studies have examined the effect of DEX on cardiac electrophysiology. ECG recording was performed in vivo and ex vivo on C57 mice. Simultaneous recording of membrane voltage (Vm) and [Ca2+]i changes was achieved with dual-dye optical mapping, in which voltage- and Ca2+-sensitive dyes are employed. Simultaneous programmed electrical stimulation was used to pacing and induce arrhythmias. Simulating catecholamine-induced arrhythmias with isoprotereno (ISO) and preconditioning with DEX to investigate the antiarrhythmic effects of DEX. Our findings demonstrated that ISO increased the incidence of ventricular tachycardia or ventricular fibrillation in mice during rapid pacing stimulation. DEX preconditioning reduced the incidence of ISO-induced ventricular arrhythmias. Optical mapping with simultaneous recordings of dual dyes (Vm dye and intracellular Ca2+ dye) revealed that DEX pretreatment attenuated the ISO-induced shortening of action potential duration (APD), calcium transient duration (CaTD), and time-to-peak (TTP) of calcium transients, as well as the ISO-induced increase in repolarization heterogeneity. DEX also slowed the conduction velocity. More importantly, DEX preconditioning significantly reduced the calcium transient alternans ratio at 80-ms, 70-ms, and 60-ms pacing cycles. These findings suggest that DEX preconditioning can reduce the incidence of ventricular arrhythmias induced by acute stress simulated by ISO. Prolongation of action potential duration and calcium transient duration and the maintenance of intracellular calcium homeostasis may be the electrophysiological mechanisms involved.

Electrophysiological dynamics of salience, default mode, and frontoparietal networks during episodic memory formation and recall revealed through multi-experiment iEEG replication.

Dynamic interactions between large-scale brain networks underpin human cognitive processes, but their electrophysiological mechanisms remain elusive. The triple network model, encompassing the salience network (SN), default mode network (DMN), and frontoparietal network (FPN), provides a framework for understanding these interactions. We analyzed intracranial electroencephalography (EEG) recordings from 177 participants across four diverse episodic memory experiments, each involving encoding as well as recall phases. Phase transfer entropy analysis revealed consistently higher directed information flow from the anterior insula (AI), a key SN node, to both DMN and FPN nodes. This directed influence was significantly stronger during memory tasks compared to resting state, highlighting the AI's task-specific role in coordinating large-scale network interactions. This pattern persisted across externally driven memory encoding and internally governed free recall. Control analyses using the inferior frontal gyrus (IFG) showed an inverse pattern, with DMN and FPN exerting higher influence on IFG, underscoring the AI's unique role. We observed task-specific suppression of high-gamma power in the posterior cingulate cortex/precuneus node of the DMN during memory encoding, but not recall. Crucially, these results were replicated across all four experiments spanning verbal and spatial memory domains with high Bayes replication factors. Our findings advance understanding of how coordinated neural network interactions support memory processes, highlighting the AI's critical role in orchestrating large-scale brain network dynamics during both memory encoding and retrieval. By elucidating the electrophysiological basis of triple network interactions in episodic memory, our study provides insights into neural circuit dynamics underlying memory function and offer a framework for investigating network disruptions in memory-related disorders.

Electrophysiological dynamics of salience, default mode, and frontoparietal networks during episodic memory formation and recall revealed through multi-experiment iEEG replication

Dynamic interactions between large-scale brain networks underpin human cognitive processes, but their electrophysiological mechanisms remain elusive. The triple network model, encompassing the salience network (SN), default mode network (DMN), and frontoparietal network (FPN), provides a framework for understanding these interactions. We analyzed intracranial electroencephalography (EEG) recordings from 177 participants across four diverse episodic memory experiments, each involving encoding as well as recall phases. Phase transfer entropy analysis revealed consistently higher directed information flow from the anterior insula (AI), a key SN node, to both DMN and FPN nodes. This directed influence was significantly stronger during memory tasks compared to resting state, highlighting the AI’s task-specific role in coordinating large-scale network interactions. This pattern persisted across externally driven memory encoding and internally governed free recall. Control analyses using the inferior frontal gyrus (IFG) showed an inverse pattern, with DMN and FPN exerting higher influence on IFG, underscoring the AI’s unique role. We observed task-specific suppression of high-gamma power in the posterior cingulate cortex/precuneus node of the DMN during memory encoding, but not recall. Crucially, these results were replicated across all four experiments spanning verbal and spatial memory domains with high Bayes replication factors. Our findings advance understanding of how coordinated neural network interactions support memory processes, highlighting the AI’s critical role in orchestrating large-scale brain network dynamics during both memory encoding and retrieval. By elucidating the electrophysiological basis of triple network interactions in episodic memory, our study provides insights into neural circuit dynamics underlying memory function and offer a framework for investigating network disruptions in memory-related disorders.

Electrophysiological Characteristics and Mechanism of His-Bundle Pacing Guided by Electrocardiograms in Uninterrupted Real-Time Monitoring Technique.

His-bundle pacing (HBP) is a pacing mode that provides near-physiological pacing and has more advantages over standard right ventricle (RV) septum pacing in positive clinical results. However, traditional HBP cannot accurately and stably place the lead tip into the His-Purkinje system. Hence, this study aimed to establish a novel strategy for HBP to strike a balancebetween an excellent pacing threshold and minor injuries to the conduction system. HBP, using continuous and real-time monitoring of unipolar His-bundle (HB) electrograms along with electrocardiograms, was performed in 29 consecutive atrial fibrillation patients. We analyzed the unipolar HB intracardiac electrogram (EGM) and electrophysiological characteristics during HBP using John Jiang's connecting cable and an electrophysiology recording system. All patients were followed up for 12 months. Of the 29 patients, 28 (96.55%) successfully received HBP. Twenty-one (75%) patients were confirmed to have the negative deflection of His potential with a negative amplitude of ≥ 0.1mV in HB EGM. The subgroup with a deep negative deflection was recorded with an HBP threshold (0.71 ± 0.41V), significantly lower than those thresholds with no deep negative deflection (1.83 ± 0.76V) (p < 0.05). The selective HBP rate was significantly different between the two groups: 20 (95.24%) in the deep negative deflection group and three (42.86%) in thenon-deep negative deflection group (p < 0.05); five (17.24%) patients presented right bundle branch block (RBBB) during the lead placement. This study supports the safety and feasibility of using an uninterrupted real-time monitoring technique for HBP. An uninterrupted real-time monitoring technique can guide theaccurate placement of the HB lead and may provide abalancebetween anexcellent pacing threshold and minor injury to the conduction system.

A Preliminary Assessment on Reproducibility of Triggered Electromyography During Selective Dorsal Rhizotomy

BACKGROUND AND OBJECTIVES: Selective dorsal rhizotomy (SDR) reduces spasticity in children with spastic cerebral palsy (CP). Intraoperative neurophysiology, triggered electromyography (trigger-EMG) is crucial in guiding sensory rootlet selection, but its reproducibility during SDR surgery has not been fully investigated. The objective of this study was to evaluate the reproducibility of trigger-EMG during SDR performed in children with spastic CP. METHODS: A retrospective review was performed for cases where dorsal roots were stimulated twice 1 to 2 minutes apart during SDR using a specific protocol. With single-pulse stimulation of 0.2 ms width having a gradually increasing intensity from 0.01 mA until the EMG amplitude is &gt;200 μV. Criteria were established to evaluate trigger-EMG reproducibility. RESULTS: This study showed that the reproducibility of trigger-EMG was excellent, as the most responsive channels in the second stimulation trial were the same as those in the first one in 90.1% of the roots stimulated. In addition, the 3 most responsive channels were mostly the same between the first and second stimulation trials in 96.9% of the roots tested. Furthermore, when comparing the evoked EMG pattern since the beginning to the end point between the 2 stimulation trials in all 131 roots, the amplitudes of trigger-EMG in 3 most responsive channels were similar to each other, particularly the most responsive one. Amplitudes of each phase in each EMG evoked were also similar to each other. CONCLUSION: The excellent reproducibility of trigger-EMG, as demonstrated by its consistent activation of specific spinal motor circuits, provides a solid foundation for future research. Further investigation into the underlying electrophysiological mechanisms of this reproducibility could inform the development of more refined stimulation protocols and data analysis techniques. These advancements hold promise for enhancing the accuracy of dorsal root selection during SDR and ultimately improving clinical outcomes for patients with spastic CP.

Electrophysiological mechanisms of single-neuron stimulation using a focused femtosecond laser

Abstract Single-cell stimulation can be effective for investigating neuronal network functions and their relationship with electrophysiological properties of single neurons. Previous studies have reported external stimulation of single neurons with low invasiveness using a focused femtosecond laser. However, laser-induced stimulation mechanisms remain unclear and require further evaluation of their electrophysiological properties. In this study, we evaluated the electrical activity of femtosecond laser-irradiated single neurons using simultaneous fluorescence Ca2+ imaging and whole-cell patch-clamp recordings. Extracellular Ca2+ influx and highly frequent action potentials were observed in target neurons after laser irradiation. Upstate membrane potentials are caused by extracellular cation influx through disrupted membranes at the focal spot. These results suggest that single neurons were stimulated by a focused femtosecond laser. The proposed method is effective in clarifying information processing in the brain at the single-cell level.

SLC4A3 anion exchanger mutations associated to sudden death : short or long QT syndrome?

Abstract Introduction SLC4A3 gene codes for an (Cl-/HCO3-) exchanger present on the surface of cardiomyocytes (AE3 channel) is involved in maintaining the physiological acid-base gradient of the cardiomyocyte at rest. Loss of function of the SLC4A3 gene leading to an increase in intracellular pH has. been reported to be responsible for short QT syndrome (SQT). Methods The aim of our study was to characterize the genotype-phenotype relationships of SLC4A3 mutations identified in the French databases (Paris, Nantes and Lyon) in patients with sudden death. Through systematic exome sequencing we identified 3 new SLC4A3 variants in 3 families with a history of sudden death in two universitary hospitals. Results Family 1. The c.3209G&amp;gt;C variant (p.Gly1070Ala) in the SLC4A3 gene was identified in a 7-yo boy with VF at sleep but admitted in encephalic death. EKG showed short QT (QTc 280ms). Clinical examination, blood tests, TTE and autopsy were normal. There was no family history of sudden death. His mother had EKG evidence of SQT and was carrier the SLC4A3 mutation. She was implanted with an ICD. His two older brothers and the rest of the family had no mutation or pathological ECG and were asymptomatic. Family 2. The c.1027C&amp;gt;T (p.Arg343Cys) mutation in the SLC4A3 gene was identified in a 29-year-old man who presented with sudden death at sleep (VF). Clinical examination, blood tests, TTE and autopsy were normal. A maternal uncle died suddenly while sleeping. His two brothers (30 and 27 yo) are both carriers of the SLC4A3 mutation and exhibit SQT (QTc 320 and 330 ms respectively). TEE, Holter monitoring and stress test were normal in both. Both brothers were treated with hydroquinidine. Over a 2-year follow-up they had no symptom nor AF. Family 3. The c.1022C&amp;gt;G (p.Thr341Arg) mutation was identified in the SLC4A3 gene in a 54-yoman who presented with VF during shower but admitted in encephalic death. There was no family history of sudden death. Clinical examination, blood tests and echocardiography as well as coronary angiogram were normal. The initial ECG showed a prolonged QT interval (QTc 520 ms). QTc decreased to 480 ms in the 48 following hours. His parents and his sister as well as his 18 yo daughter have normal QTc values. We are awaiting the genetic results. Conclusion Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 has been recently reported to cause short QT syndrome but it seems that in rare cases it may also be responsible for LQTS. Further patients are needed to confirm these data. In order to understand the underlying electrophysiological mechanisms, we plan to characterize the cellular impact of these new mutations through IPS.

Surgical treatment of long-term epilepsy-associated tumors guided by stereoelectroencephalography

PurposeAccurate detection and resection of the epileptogenic zone (EZ) in patients with long-term epilepsy-associated tumors (LEATs) are significantly correlated with favorable seizure prognosis. However, the relationship between tumors and the EZ remains unknown. This study aimed to evaluate the spatial relationship between LEATs and the EZ, as well as the electrophysiological features of LEATs.MethodsWe retrospectively studied five patients with LEATs who underwent deep electrode implantation and EZ resection in the hospital. The clinical characteristics, surgical outcomes, localizing features and intracranial SEEG results were reviewed.ResultsOne female and four males (mean age: 25.2 years; median age: 24 years; range: 13–45 years) were included in the study. Five-to-eleven electrodes (mean: 8.4) were implanted per patient. The EZ was located in the tumor and nearby cortex in three cases and in the tumor and distant areas in two cases. Pathological examination revealed ganglioglioma in four cases, two of which were associated with hippocampal sclerosis, and the other case showed a multinodular and vacuolating neuronal tumor with gliosis. All patients were seizure-free for at least 24 months postoperatively.ConclusionsSEEG provides valuable insights into the electrophysiological mechanisms of LEATs. The EZ often contains brain tissue around the tumor. However, only a few cases, particularly those with temporoparietal occipital (TPO) area involvement, a long history of epilepsy and other abnormalities on MRI, such as hippocampal sclerosis and focal cortical dysplasia, may include distant areas.

Translation of pathophysiological mechanisms of atrial fibrosis into new diagnostic and therapeutic approaches.

Atrial fibrosis is one of the main manifestations of atrial cardiomyopathy, an array of electrical, mechanical and structural alterations associated with atrial fibrillation (AF), stroke and heart failure. Atrial fibrosis can be both a cause and a consequence of AF and, once present, it accelerates the progression of AF. The pathophysiological mechanisms leading to atrial fibrosis are diverse and include stretch-induced activation of fibroblasts, systemic inflammatory processes, activation of coagulation factors and fibrofatty infiltrations. Importantly, atrial fibrosis can occur in different forms, such as reactive and replacement fibrosis. The diversity of atrial fibrosis mechanisms and patterns depends on sex, age and comorbidity profile, hampering the development of therapeutic strategies. In addition, the presence and severity of comorbidities often change over time, potentially causing temporal changes in the mechanisms underlying atrial fibrosis development. This Review summarizes the latest knowledge on the molecular and cellular mechanisms of atrial fibrosis, its association with comorbidities and the sex-related differences. We describe how the various patterns of atrial fibrosis translate into electrophysiological mechanisms that promote AF, and critically appraise the clinical applicability and limitations of diagnostic tools to quantify atrial fibrosis. Finally, we provide an overview of the newest therapeutic interventions under development and discuss relevant knowledge gaps related to the association between clinical manifestations and pathological mechanisms of atrial fibrosis and to the translation of this knowledge to a clinical setting.

Migraine and epilepsy frontiers, new challenges in its understanding: A case report

The relationship between migraine and epilepsy has been recognized since the 20th century. Currently, both pathologies share several characteristics, from molecular and electrophysiological mechanisms to their similarity in clinical symptoms and response to treatment. This is a case report of an 11-year-old male patient who presented with focal epilepsy at the age of 8 years. One year later, he developed episodes of migraine without aura followed by seizures with a frequency of 1–2 times per month, with headache duration ranging from 10 min to 6 h. At age 11, he also presented other episodes in which the headache occurred after the epileptic event and other episodes in which the headache was present both before and after the epileptic seizure. An interictal EEG study and an EEG study during a migraine attack showed the presence of high-voltage theta activity and bilateral temporo-parieto-occipital spikes with a greater expression in the right cerebral hemisphere. To our knowledge, this is the first report of an atypical presentation of migraine without aura and epileptic seizure. This case opens new challenges in the search for understanding between both pathologies.

The mechanisms of effects of oil-derived polyaromatic hydrocarbons on cardiac electrical activity in navaga cod (Eleginus nawaga)

The intensive development of oil and gas industries in the Arctic threatens Arctic aquatic ecosystems. The toxic and primarily lethal cardiotoxic effects of oil in living organisms are believed to be associated with polyaromatic hydrocarbons (PAHs), and previous works revealed the electrophysiological mechanisms of action of individual oil-derived PAHs. However, the physiological effects of a complex PAHs mixture in oil water-soluble fraction (WSF) have not been previously studied. This study is focused on the effects of oil WSF on electrical activity and major ionic currents in the working myocardium of navaga (Eleginus nawaga), which is one of the most important commercial fish species in the Arctic. We found that 1% and 10% solutions of oil WSF cause a marked increase in the duration of action potentials (APs) in navaga cardiomyocytes. This effect appears to be due to the suppression of rapid delayed rectifying current IKr (IC50 about 3% in ventricular and atrial myocardium). At higher concentrations, oil WSF also suppressed calcium current ICaL (IC50 = 10.6%), which led to a decrease in the contractile activity in isolated myocardial preparations. Unlike individual tricyclic PAHs, oil WSF did not affect fast sodium current INa and AP upstroke velocity. An assessment of the content of tricyclic PAHs in 10% solution of oil WSF showed that their total concentration is relatively low and does not exceed 100 nM. Thus, oil WSF also has a powerful cardiotoxic effect in fish myocardium, but its effects differ from the previously studied effects of tricyclic PAHs and suggest the presence of yet unexplored oil compounds that have a more powerful toxic potential against ERG channels.

Electrophysiological and hemodynamic mechanisms underlying load modulations in visuospatial working memory: A functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG) study.

The n-back task has been widely used to study working memory. Previous studies investigating the electrophysiological (electroencephalogram [EEG]) and hemodynamic correlates (functional near-infrared spectroscopy [fNIRS]) of the n-back task have been generally based on verbal stimuli and only investigated EEG frequency bands. We simultaneously acquired the EEG and fNIRS in 35 participants (16 males; age = 26.4 ± 4.3 years; educational attainment = 18 ± 2 years) during a visuospatial n-back task. The task encompassed a control condition and a low (requiring to recall one previous stimulus) and a high (requiring to recall two previous stimuli) working memory load experimental conditions. Accuracy decreased and reaction times slowed in the high compared to both low load and control conditions. Regarding EEG, P3a showed higher amplitude in the experimental conditions compared to the control one, and P3b exhibited higher amplitude in the low compared to the high load condition. Regarding fNIRS, the high load condition showed higher deoxygenated hemoglobin compared to the control one. Moreover, the central frontopolar cortex showed higher activation compared with the left frontal cortex. Our study showed that working memory load during a visuospatial n-back task influenced behavioral and electrophysiological indices. Even if the load effect was only observed for deoxygenated hemoglobin on hemodynamic data, this was in line with previous studies and coherent with its electrophysiological correlates. Thus, our study confirms that EEG and fNIRS can be successfully used in multimodal acquisitions, but also highlights that future studies are needed to develop a novel version of the task. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Electrophysiological dynamics of salience, default mode, and frontoparietal networks during episodic memory formation and recall: A multi-experiment iEEG replication.

Dynamic interactions between large-scale brain networks underpin human cognitive processes, but their electrophysiological mechanisms remain elusive. The triple network model, encompassing the salience (SN), default mode (DMN), and frontoparietal (FPN) networks, provides a framework for understanding these interactions. We analyzed intracranial EEG recordings from 177 participants across four diverse episodic memory experiments, each involving encoding as well as recall phases. Phase transfer entropy analysis revealed consistently higher directed information flow from the anterior insula (AI), a key SN node, to both DMN and FPN nodes. This directed influence was significantly stronger during memory tasks compared to resting-state, highlighting the AI's task-specific role in coordinating large-scale network interactions. This pattern persisted across externally-driven memory encoding and internally-governed free recall. Control analyses using the inferior frontal gyrus (IFG) showed an inverse pattern, with DMN and FPN exerting higher influence on IFG, underscoring the AI's unique role. We observed task-specific suppression of high-gamma power in the posterior cingulate cortex/precuneus node of the DMN during memory encoding, but not recall. Crucially, these results were replicated across all four experiments spanning verbal and spatial memory domains with high Bayes replication factors. Our findings advance understanding of how coordinated neural network interactions support memory processes, highlighting the AI's critical role in orchestrating large-scale brain network dynamics during both memory encoding and retrieval. By elucidating the electrophysiological basis of triple network interactions in episodic memory, our study provides insights into neural circuit dynamics underlying memory function and offer a framework for investigating network disruptions in memory-related disorders.

Machine Learning Elucidates Electrophysiological Properties Predictive of Multi- and Single-Firing Human and Mouse Dorsal Root Ganglia Neurons.

Human and mouse dorsal root ganglia (hDRG and mDRG) neurons are important tools in understanding the molecular and electrophysiological mechanisms that underlie nociception and drive pain behaviors. One of the simplest differences in firing phenotypes is that neurons are single-firing (exhibit only one action potential) or multi-firing (exhibit 2 or more action potentials). To determine if single- and multi-firing hDRG neurons exhibit differences in intrinsic properties, firing phenotypes, and AP waveform properties, and if these properties could be used to predict multi-firing, we measured 22 electrophysiological properties by whole-cell patch-clamp electrophysiology of 94 hDRG neurons from six male and four female donors. We then analyzed the data using several machine learning models to determine if these properties could be used to predict multi-firing. We used 1,000 iterations of Monte Carlo cross-validation to split the data into different train and test sets and tested the logistic regression, k-nearest neighbors, random forest, support vector classifier, and XGBoost machine learning models. All models tested had a >80% accuracy on average, with support vector classifier, and XGBoost performing the best. We found that several properties correlated with multi-firing hDRG neurons and together could be used to predict multi-firing neurons in hDRG including a long decay time, a low rheobase, and long first spike latency. We also found that the hDRG models were able to predict multi-firing with 90% accuracy in mDRG neurons. Understanding these properties could be beneficial in the elucidation of targets on peripheral sensory neurons related to pain.