Spontaneous Electrical Activity Research Articles

Features of the Background EEG of Alcohol Dependent Patients with Comorbid Exogenous Organic Brain Damage

Background: the range and prevalence of complicating pathologies in alcoholism indicate the need for a thorough examination of patients using modern diagnostic approaches. The aim was to study the indicators of spontaneous electrical activity of the brain in patients with alcohol dependence with comorbid exogenous organic brain damage non-alcoholic nature. Patients and methods: a study of electroencephalograms of 148 men with alcohol dependence using the classification of E.A. Zhirmunskaya (1984) was conducted. Results: based on the hystory data, 85 (57.4%) patients were found to have exogenous organic vascular brain damage (including hypertension in 57 (38.5%) cases, chronic cerebral circulation disorder — in 8 (5.4%), somatoform autonomic dysfunction — in 7 (4.7%)) and traumatic character (mild traumatic brain injury) in 13 (8.8%)) patients. The analysis using Fisher’s exact criterion revealed statistically significant differences between patients with alcohol dependence and alcoholism patients with comorbid exogenous organic brain damage in the frequency of occurrence of various types of electroencephalograms (p < 0.001). The study clearly showed that the presence of exogenous organic brain damage in patients with alcoholism leads to more pronounced functional changes in the brain. Conclusion: early detection of pathological activity on the EEG in patients with alcohol dependence will allow clinicians to carry out appropriate therapeutic and diagnostic measures in a timely manner and will provide additional information necessary for the development of personalized medical rehabilitation programs for patients taking into account their neurophysiological profile.

Modeling sporadic juvenile ALS in iPSC-derived motor neurons explores the pathogenesis of FUSR503fs mutation.

Fused in sarcoma (FUS) mutations represent the most common genetic etiology of juvenile amyotrophic lateral sclerosis (JALS), for which effective treatments are lacking. In a prior report, we identified a novel FUS mutation, c.1509dupA: p. R503fs (FUSR503fs), in a sporadic JALS patient. The physicochemical properties and structure of FUSR503fs protein were analyzed by software: Multi-electrode array (MEA) assay, calcium activity imaging assay and transcriptome analysis were used to explore the pathophysiological mechanism of iPSC derived motor neurons. Structural analysis and predictions regarding physical and chemical properties of this mutation suggest that the reduction of phosphorylation and glycosylation sites, along with alterations in the amino acid sequence, may contribute to abnormal FUS accumulation within the cytoplasm and nucleus of induced pluripotent stem cell- derived motor neurons (MNs). Multi-electrode array and calcium activity imaging indicate diminished spontaneous electrical and calcium activity signals in MNs harboring the FUSR503fs mutation. Transcriptomic analysis reveals upregulation of genes associated with viral infection and downregulation of genes involved in neural function maintenance, such as the ATP6V1C2 gene. Treatment with ropinirole marginally mitigates the electrophysiological decline in FUSR503fs MNs, suggesting the utility of this cell model for mechanistic exploration and drug screening. iPSCs-derived motor neurons from JALS patients are promising tools for drug screening. The pathological changes in motor neurons of FUSR503fs may occur earlier than in other known mutation types that have been reported.

The contribution of EEG to assess and treat motor disorders in multiple sclerosis

ObjectiveElectroencephalography (EEG) can highlight significant changes in spontaneous electrical activity of the brain produced by altered brain network connectivity linked to inflammatory demyelinating lesions and neuronal loss occurring in multiple sclerosis (MS). In this review, we describe the main EEG findings reported in the literature to characterize motor network alteration in term of local activity or functional connectivity changes in patients with MS (pwMS). MethodsA comprehensive literature search was conducted to include articles with quantitative analyses of resting-state EEG recordings (spectrograms or advanced methods for assessing spatial and temporal dynamics, such as coherence, theory of graphs, recurrent quantification, microstates) or dynamic EEG recordings during a motor task, with or without connectivity analyses. ResultsIn this systematic review, we identified 26 original articles using EEG in the evaluation of MS-related motor disorders. Various resting or dynamic EEG parameters could serve as diagnostic biomarkers of motor control impairment to differentiate pwMS from healthy subjects or be related to a specific clinical condition (fatigue) or neuroradiological aspects (lesion load). ConclusionsWe highlight some key EEG patterns in pwMS at rest and during movement, both suggesting an alteration or disruption of brain connectivity, more specifically involving sensorimotor networks. SignificanceSome of these EEG biomarkers of motor disturbance could be used to design future therapeutic strategies in MS based on neuromodulation approaches, or to predict the effects of motor training and rehabilitation in pwMS.

Intranasal delivery of shRNA to knockdown the 5HT-2A receptor enhances memory and alleviates anxiety

Short-hairpin RNAs (shRNA), targeting knockdown of specific genes, hold enormous promise for precision-based therapeutics to treat numerous neurodegenerative disorders. However, whether shRNA constructed molecules can modify neuronal circuits underlying certain behaviors has not been explored. We designed shRNA to knockdown the human HTR2A gene in vitro using iPSC-differentiated neurons. Multi-electrode array (MEA) results showed that the knockdown of the 5HT-2A mRNA and receptor protein led to a decrease in spontaneous electrical activity. In vivo, intranasal delivery of AAV9 vectors containing shRNA resulted in a decrease in anxiety-like behavior in mice and a significant improvement in memory in both mice (104%) and rats (92%) compared to vehicle-treated animals. Our demonstration of a non-invasive shRNA delivery platform that can bypass the blood–brain barrier has broad implications for treating numerous neurological mental disorders. Specifically, targeting the HTR2A gene presents a novel therapeutic approach for treating chronic anxiety and age-related cognitive decline.

Treatment of Chronic Muscle Spasm Secondary to Chemotherapy – A Case Report

A known common complication of chemotherapy is the development of muscle spasms. The etiology of which may be multifactorial. However, unlike spasticity secondary to stroke, chronic muscle spasms are not maintained by neurological impulses or lack thereof. Chronic muscle spasms are maintained by continuous spontaneous electrical activity (SEA) throughout the body of the muscle. I have proposed the underlying cause for the SEA is muscle ischemia and the SEA is essentially an arrhythmia similar to what is seen with arrhythmias caused by cardiac ischemia [01]. Regardless of the initial insult that results in chronic muscle spasm, the spasm takes on a life of its own

Assessment of the Effects of Sphingosine Kinase 1/Sphingosine-1-Phosphate on Microangiogenesis at Rat Myofascial Trigger Points Using Contrast-Enhanced Ultrasonography.

Few studies have assessed the effects of sphingosine kinase 1/sphingosine-1-phosphate (SPHK1/S1P) on microangiogenesis at rat myofascial trigger points (MTrPs) using contrast-enhanced ultrasonography (CEUS). This study aimed to address these deficiencies. Here, we investigated the effects of SPHK1/S1P on MTrP microangiogenesis and the value of CEUS in evaluating these effects. Forty Sprague‒Dawley rats were subdivided into two groups: control and MTrP groups. MTrPs were established by 8 weeks of the strike procedure combined with eccentric motion and 4 weeks of recovery. All rats were euthanized after having undergone CEUS with an overdose of pentobarbital sodium. MTrP and control tissue samples were removed for haematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) imaging. The tissue was dehydrated, cleared, and embedded before sectioning. The sections were then incubated overnight at 4°C, and immunohistochemistry was carried out with primary antibodies including rabbit anti-CD31, rabbit anti-SPHK1and rabbit anti-S1PR1. MTrP rats exhibited spontaneous electrical activity (SEA) and a local twitch response (LTR) during electromyography (EMG) examination. The CEUS time-intensity curves (TICs) showed that the perfusion intensity in the MTrPs and surrounding tissue area was increased, with faster perfusion than in normal sites, while the TICs in the control group slowly increased and then slowly decreased. The correlation coefficient between the microvessel density (MVD) and sphingosine 1-phosphate receptor 1 (S1PR1) was 0.716 (p <0.01). Spearman correlation analysis revealed that Spearman's rho (ρ) values between the MVD and peak intensity (PI), between the MVD and area under the curve (AUC), and between the MVD and SPHK1 were > 0.5 (p <0.05), > 0.7 (p <0.01), and > 0.7 (p <0.01), respectively. CEUS is valuable for detecting microangiogenesis within MTrPs, and SPHK1/S1P plays an important role in promoting MTrP tissue microangiogenesis.

The influence of sentence focus on motor system activity in language comprehension and its temporal dynamics: Preliminary evidence from sEMG

Previous research has shown that individual experiences and experimental tasks can influence the occurrence of mental simulation during sentence comprehension. However, little research has focused on the effect of sentence focus on mental simulation and its temporal dynamics. Sentence focus refers to the hierarchical structure of information within a sentence, where focused information represents the most prominent and essential information. In contrast, nonfocused information provides a background for the focused information. The present study investigated whether sentence focus would affect the activity of the motor system in language comprehension and at which stage the effect of sentence focus occurred. We measured spontaneous arm muscle electrical activity by surface electromyography (sEMG) while participants read action-focused, nonaction-focused, and control sentences. We observed greater spontaneous muscle electrical activity in the flexor common muscle of the fingers when participants read action-focused sentences compared to nonaction-focused and control sentences. Additionally, there was an interactive trend between sentence type and time, spontaneous muscle electrical activity while reading action-focused sentences was observed in both early (1 ms to 300 ms after the presentation of the action phrase) and late time windows (901 ms to 1500 ms after the action phrase). The findings suggest that the motor system exhibits flexible engagement during language comprehension and the impact of sentence focus on motor system activity may be throughout both the lexical-semantic retrieval and sentence-meaning integration stages.

Simulation and fabrication of in vitro microfluidic microelectrode array chip for patterned culture and electrophysiological detection of neurons

To enable the detection and modulation of modularized neural networks in vitro, this study proposes a microfluidic microelectrode array chip for the cultivation, compartmentalization, and control of neural cells. The chip was designed based on the specific structure of neurons and the requirements for detection and modulation. Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software, and the simulation results show that the liquid within the chip can flow smoothly, ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels. By employing MEMS technology in combination with nanomaterial modification techniques, the microfluidic microelectrode array chip was fabricated successfully. Primary hippocampal neurons were cultured on the chip, forming a well-defined neural network. Spontaneous electrical activity of the detected neurons was recorded, exhibiting a 23.7% increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array. This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro, potentially serving as a novel tool in neuroscience research.

DiffMDD: A Diffusion-Based Deep Learning Framework for MDD Diagnosis Using EEG.

Major Depression Disorder (MDD) is a common yet destructive mental disorder that affects millions of people worldwide. Making early and accurate diagnosis of it is very meaningful. Recently, EEG, a non-invasive technique of recording spontaneous electrical activity of brains, has been widely used for MDD diagnosis. However, there are still some challenges in data quality and data size of EEG: (1) A large amount of noise is inevitable during EEG collection, making it difficult to extract discriminative features from raw EEG; (2) It is difficult to recruit a large number of subjects to collect sufficient and diverse data for model training. Both of the challenges cause the overfitting problem, especially for deep learning methods. In this paper, we propose DiffMDD, a diffusion-based deep learning framework for MDD diagnosis using EEG. Specifically, we extract more noise-irrelevant features to improve the model's robustness by designing the Forward Diffusion Noisy Training Module. Then we increase the size and diversity of data to help the model learn more generalized features by designing the Reverse Diffusion Data Augmentation Module. Finally, we re-train the classifier on the augmented dataset for MDD diagnosis. We conducted comprehensive experiments to test the overall performance and each module's effectiveness. The framework was validated on two public MDD diagnosis datasets, achieving the state-of-the-art performance.

Silicate Microfiber Scaffolds Support the Formation and Expansion of the Cortical Neuronal Layer of Cerebral Organoids With a Sheet-Like Configuration.

Cerebral organoids (COs) are derived from human-induced pluripotent stem cells in vitro and mimic the features of the human fetal brain. The development of COs is largely dependent on "self-organization" mechanisms, in which differentiating cells committed to cortical cells autonomously organize into the cerebral cortex-like tissue. However, extrinsic manipulation of their morphology, including size and thickness, remains challenging. In this study, we discovered that silicate microfiber scaffolds could support the formation of cortical neuronal layers and successfully generated cortical neuronal layers, which are 9 times thicker than conventional COs, in 70 days. These cortical neurons in the silicate microfiber layer were differentiated in a fetal brain-like lamination pattern. While these cellular characteristics such as cortical neurons and neural stem/progenitor cells were like those of conventional COs, the cortical neuronal layers were greatly thickened in sheet-like configuration. Moreover, the cortical neurons in the scaffolds showed spontaneous electrical activity. We concluded that silicate microfiber scaffolds support the formation of the cortical neuronal layers of COs without disturbing self-organization-driven corticogenesis. The extrinsic manipulation of the formation of the cortical neuronal layers of COs may be useful for the research of developmental mechanisms or pathogenesis of the human cerebral cortex, particularly for the development of regenerative therapy and bioengineering.

Hyperexcitability of muscle spindle afferents in jaw-closing muscles in experimental myalgia: Evidence for large primary afferents involvement in chronic pain.

The goals of this review are to improve understanding of the aetiology of chronic muscle pain and identify new targets for treatments. Muscle pain is usually associated with trigger points in syndromes such as fibromyalgia and myofascial syndrome, and with small spots associated with spontaneous electrical activity that seems to emanate from fibers inside muscle spindles in EMG studies. These observations, added to the reports that large-diameter primary afferents, such as those innervating muscle spindles, become hyperexcitable and develop spontaneous ectopic firing in conditions leading to neuropathic pain, suggest that changes in excitability of these afferents might make an important contribution to the development of pathological pain. Here, we review evidence that the muscle spindle afferents (MSAs) of the jaw-closing muscles become hyperexcitable in a model of chronic orofacial myalgia. In these afferents, as in other large-diameter primary afferents in dorsal root ganglia, firing emerges from fast membrane potential oscillations that are supported by a persistent sodium current (INaP ) mediated by Na+ channels containing the α-subunit NaV 1.6. The current flowing through NaV 1.6 channels increases when the extracellular Ca2+ concentration decreases, and studies have shown that INaP -driven firing is increased by S100β, an astrocytic protein that chelates Ca2+ when released in the extracellular space. We review evidence of how astrocytes, which are known to be activated in pain conditions, might, through their regulation of extracellular Ca2+ , contribute to the generation of ectopic firing in MSAs. To explain how ectopic firing in MSAs might cause pain, we review evidence supporting the hypothesis that cross-talk between proprioceptive and nociceptive pathways might occur in the periphery, within the spindle capsule.

Interhemispheric connectivity dynamics of brain activity indused by cortical spreading depolarization in rats

Growing experimental and clinical evidence indicates the crucial role of network dysfunction in neurological disorders’ pathogenesis, including migraine, one of the most prevalent chronic brain diseases. Episodic headache attacks, frequently unilateral, accompanied by an aura, are associated with migraine. Migraine aura is a neurological condition characterized by the temporary development of unilateral sensory, motor, and/or speech disturbances. The symptoms are thought to indicate transient cerebral dysfunction in the cerebral cortex resulting from cortical spreading depolarization (SD), a wave of strong cellular depolarization that gradually spreads through the cortex at a rate of 3–5 mm/min. Electrophysiologically, the cortical SD wave is revealed by a high-amplitude slow negative shift in the extracellular potential and temporary suppression of the electrical activity of the cortex (EEG depression). The change in extracellular potential is associated with strong neuroglial depolarization and disruption of local ion homeostasis, which lasts for 1–2 min in healthy neuronal tissue. The SD results in a momentary suppression of the spontaneous electrical activity within the cortex, which is preceded by a brief excitation of the neurons. The neurological symptoms of the aura suggest a unilateral impairment of interhemispheric interactions during the early phase of a migraine attack. Our study investigated the effect of unilateral SD (a probable pathophysiological mechanism of migraine aura) on interhemispheric functional communication in freely behaving rats using local field potentials of the visual and motor cortex. Two methods were used to examine connectivity: mutual information function, computed using the method proposed in [1], and phase synchronization, calculated through the method [2], for four frequency bands: delta (1–4 Hz), theta (4–10 Hz), beta (10–25 Hz), and gamma (25–50 Hz). This was done by performing calculations on non-overlapping twenty-second intervals. Functional connectivity evolution was analyzed using local field potential records collected from homotopic points of the motor and visual cortex of two hemispheres in freely moving rats after inducing a single unilateral cortical SD in the somatosensory cortex. Cortical SD caused a significant wide-band decline (3–4 times) in interhemispheric functional connectivity in both the visual and motor cortex areas. Following the depolarization wave, the functional decoupling of the hemispheres began and progressively intensified, concluding by 5 min after the induction of the cortical SD wave. The network impairment displayed region- and frequency-specific features, with greater prominence observed in the visual cortex than in the motor cortex. The decline in functional connectivity was concurrent with abnormal animal behavior and aberrant activity in the ipsilateral cortex that appeared after the SD wave had ended. The study indicated that unilateral SD leads to a reversible decline in the functional interhemispheric connectivity in the awake animal cortex. Given the crucial role of synchronizing cortical oscillations for processing sensory information and integrating sensorimotor functions, the intracortical functional interactions disruption resulting from a unilateral SD wave, which we discovered in our present study, could contribute to the neuropathological mechanisms of migraine aura and sensory processing dysfunction during a migraine attack.

Electrogastrography in patients with gastric motility disorders.

Electrogastrography (EGG) is a novel diagnostic modality for assessing the gastrointestinal tract (GI) that generates spontaneous electrical activity and monitors gastric motility. The aim of this study was to compare patients with functional dyspepsia (FD) and diabetic gastroparesis (D-GP) with healthy controls (CT) to use established findings on abnormalities of gastric motility based on EGG characteristics. In this study, 50 patients with FD, 50 D-GP patients, and 50 CT subjects were studied to compare EGG with discrete wavelet transform models (DWT) to extract signal characteristics using a variety of different qualitative and quantitative metrics from pre-prandial and postprandial states. As a result, higher statistically significant (p < 0.05*) were found in the DWT models based on power spectral density (PSD) analysis in both states. We also present that the correlations between EGG metrics and the presence of FD, D-GP, and CT symptoms were inconsistent. This paper represents that EGG assessments of FD and D-GP patients differ from healthy controls in terms of abnormalities of gastric motility. Additionally, we demonstrate that diverse datasets showed adequate gastric motility responses to a meal. We anticipate that our method will provide a comprehensive understanding of gastric motility disorders for better treatment and monitoring in both clinical and research settings. In conclusion, we present potential future opportunities for precise gastrointestinal electrophysiological disorders.

Antineutrophil cytoplasmic antibody-associated vasculitis with predominant truncal muscle weakness: a retrospective case series.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) frequently leads to mononeuritis multiplex, which are characterized by distal weakness associated with sensory disturbances. Although AAV has also been reported to be associated with myopathy, the pathogenesis and characteristics remain unclear. We aimed to show the clinical and laboratory findings in AAV-associated myopathy. This retrospective single-center study included patients with the diagnosis of AAV who had been admitted to the neurology department and had biopsy specimens of muscle and/or nerve tissue. We identified four patients with a distinct clinical presentation of muscle weakness in the trunk and proximal limbs. The weakness resembled that of inflammatory muscle disease. These patients denied symptoms associated with neuropathy, and had normal serum creatine kinase (CK) levels. Needle electromyography (needle EMG) showed spontaneous electrical activity at rest, and results of magnetic resonance imaging (MRI) suggested inflammatory myopathy. Muscle biopsy specimens from all four patients revealed vasculitis and inflammation in proximity to the affected vessels, without any discernible characteristics of other myopathies. The patients also complained of symptoms affecting other organs, such as the ears and kidneys, which is typical of AAV cases. Remission induction therapy, such as cyclophosphamide pulse therapy in addition to oral prednisolone, were effective for all four patients. However, relapses occurred in two patients during maintenance therapy and two patients died of aspiration pneumonia. The clinical course of our patients might represent a subtype of AAV that is characterized by muscle weakness of the trunk and proximal extremities and arises from vasculitis within the muscles. The clinical manifestations of our patients were similar to those of patients with inflammatory myopathy with regard to the distribution of muscle weakness, MRI and needle EMG findings. However, there are notable differences between AAV associated myopathy vs. inflammatory myositis like dermatomyositis; (1) the absence of elevated CK levels, (2) the presence of complications in other organs, (3) distinct pathological findings, and (4) severe outcomes. Awareness that AAV patients with muscle involvement could have a subtype of AAV that seriously affects various organs is critical for an accurate diagnosis and effective therapeutic management.

Clinical manifestations and mechanisms of formation of neurological disorders in patients with vibration disease

The review presents an analysis of literature sources devoted to the study of changes in the nervous system in patients with vibration disease. Vibration-mediated cellular hypoxia, which occurs as a result of spastic changes in blood vessels, phase fluctuations in intravascular pressure, impaired blood and lymph outflow, causes suppression of energy metabolism, contributes to disorders at the level of receptor (glutamate, GABA-ergic, dopamine and cholinergic) and synaptic structures, conductors of pain and temperature sensitivity (demyelinization), analyzing neurons in the parietal region of the brain, regulatory proteins of the nervous tissue (NF-200, GFAP S-100). A low-amplitude, irregular, disorganized and sometimes deformed EEG spectrum with a predominance of the alpha wave and a shift of the alpha rhythm to the left reflects changes in the spontaneous electrical activity of brain structures in patients. With an increase in the experience dose of vibration-noise exposure, the dominant alpha activity changes to slow-wave or polyrhythmic. Mild and moderate diffuse changes in the brain become focal in nature, cortical-subcortical relationships are disrupted at the diencephalic level, creating a pathophysiological basis for sensorineural (sensory-neural) hearing loss, especially in patients with a genetic predisposition mediated by genes encoding proteins of the heat shock system. The psycho-emotional status of patients is characterized by a hypochondriacal focus on the state of health, mental disadaptation, psycho-emotional disorders in the form of anxiety, depressive mood. The analysis of literature sources on the mechanisms of the formation of neurological disorders in patients with vibration disease revealed the lack of data on the state of the multicomponent ghrelin system interacting with GHSR-1A and GHSR-1B receptors, which determines a new vector in further experimental and clinical studies.

Alternating current stimulation promotes neurite outgrowth and plasticity in neurons through activation of the PI3K/AKT signaling pathway.

As a commonly used physical intervention, electrical stimulation (ES) has been demonstrated to be effective in the treatment of central nervous system disorders. Currently, researchers are studying the effects of electrical stimulation on individual neurons and neural networks, which are dependent on factors such as stimulation intensity, duration, location, and neuronal properties. However, the exact mechanism of action of electrical stimulation remains unclear. In some cases, repeated or prolonged electrical stimulation can lead to changes in the morphology or function of the neuron. In this study, immunofluorescence staining and Sholl analysis are used to assess changes in the neurite number and axon length to determine the optimal pattern and stimulation parameters of ES for neurons. Neuronal death and plasticity are detected by TUNEL staining and microelectrode array assays, respectively. mRNA sequencing and bioinformatics analysis are applied to predict the key targets of the action of ES on neurons, and the identified targets are validated by western blot analysis and qRT-PCR. The effects of alternating current stimulation (ACS) on neurons are more significant than those of direct current stimulation (DCS), and the optimal parameters are 3 μA and 20 min. ACS stimulation significantly increases the number of neurites, the length of axons and the spontaneous electrical activity of neurons, significantly elevates the expression of growth-associated protein-43 (GAP-43) without significant changes in the expression of neurotrophic factors. Furthermore, application of PI3K/AKT-specific inhibitors significantly abolishes the beneficial effects of ACS on neurons, confirming that the PI3K/AKT pathway is an important potential signaling pathway in the action of ACS.

Multiple neuron clusters on Micro-Electrode Arrays as an in vitro model of brain network

Understanding the brain functioning is essential for governing brain processes with the aim of managing pathological network dysfunctions. Due to the morphological and biochemical complexity of the central nervous system, the development of general models with predictive power must start from in vitro brain network engineering. In the present work, we realized a micro-electrode array (MEA)-based in vitro brain network and studied its emerging dynamical properties. We obtained four-neuron-clusters (4N) assemblies by plating rat embryo cortical neurons on 60-electrode MEA with cross-shaped polymeric masks and compared the emerging dynamics with those of sister single networks (1N). Both 1N and 4N assemblies exhibited spontaneous electrical activity characterized by spiking and bursting signals up to global activation by means of network bursts. Data revealed distinct patterns of network activity with differences between 1 and 4N. Rhythmic network bursts and dominant initiator clusters suggested pacemaker activities in both assembly types, but the propagation of activation sequences was statistically influenced by the assembly topology. We proved that this rhythmic activity was ivabradine sensitive, suggesting the involvement of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, and propagated across the real clusters of 4N, or corresponding virtual clusters of 1N, with dominant initiator clusters, and nonrandom cluster activation sequences. The occurrence of nonrandom series of identical activation sequences in 4N revealed processes possibly ascribable to neuroplasticity. Hence, our multi-network dissociated cortical assemblies suggest the relevance of pacemaker neurons as essential elements for generating brain network electrophysiological patterns; indeed, such evidence should be considered in the development of computational models for envisaging network behavior both in physiological and pathological conditions.

Left cardiac vagotomy rapidly reduces contralateral cardiac vagal electrical activity in anesthetized Göttingen minipigs

BackgroundThe impact of acute unilateral injury on spontaneous electrical activity in both vagus nerves at the heart level is poorly understood. We investigated the immediate neuroelectrical response after right or left cardiac vagal nerve transection (VNTx) by recording spiking activity of each heart vagus nerve (VN). MethodsFourteen male Göttingen minipigs underwent sternotomy. Multi-electrode cuffs were implanted below the cut level to record vagal electroneurographic signals during electrocardiographic and hemodynamic monitoring, before and immediately after cardiac VNTx (left: L-cut, n = 6; right: R-cut, n = 8). ResultsLeft cardiac VNTx significantly reduced multi-unit electrical activity (MUA) firing rate in the vagal stump (−30.7% vs pre-cut) and intact right VN (−21.8% vs pre-cut) at the heart level, without affecting heart rate, heart rate variability, or hemodynamics. In contrast, right cardiac VNTx did not acutely alter MUA in either VN but slightly increased (p < 0.022) the root mean square of successive RR interval differences (rMSSD), an index of parasympathetic outflow, without affecting hemodynamics. ConclusionsOur study reveals an early left-lateralized pattern in vagal spiking activity following unilateral cardiac vagotomy. These findings enhance understanding of the neuroelectrical response to vagal injury and provide insights into preserving vagal outflow after unilateral cardiac vagotomy. Importantly, monitoring spiking activity of the cardiac right VN may predict onset of left vagal pathway injury, which is detrimental to cardiac patients and can occur as a complication of catheter ablation for atrial fibrillation.

Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells.

The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate (ATP) by supporting cells in the Kölliker's organ. However, the mechanisms responsible for initiating spontaneous ATP release have not been determined. Our previous study revealed that telomerase reverse transcriptase (TERT) is expressed in the basilar membrane during the first postnatal week. Its role in cochlear development remains unclear. In this study, we investigated the expression and role of TERT in postnatal cochlea supporting cells. Our results revealed that in postnatal cochlear Kölliker's organ supporting cells, TERT shifts from the nucleus into the cytoplasm over time. We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo. Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis, suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions. We observed increased ATP synthesis, release and activation of purine signaling systems in supporting cells during the first 10 postnatal days. The phenomenon that TERT translocation coincided with changes in ATP synthesis, release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system. Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.

In vitro exposure of neuronal networks to the 5G-3.5 GHz signal.

The current deployment of the fifth generation (5G) of wireless communications raises new questions about the potential health effects of exposure to radiofrequency (RF) fields. So far, most of the established biological effects of RF have been known to be caused by heating. We previously reported inhibition of the spontaneous electrical activity of neuronal networks in vitro when exposed to 1.8 GHz signals at specific absorption rates (SAR) well above the guidelines. The present study aimed to assess the effects of RF fields at 3.5 GHz, one of the frequencies related to 5G, on neuronal activity in-vitro. Potential differences in the effects elicited by continuous-wave (CW) and 5G-modulated signals were also investigated. Spontaneous activity of neuronal cultures from embryonic cortices was recorded using 60-electrode multi-electrode arrays (MEAs) between 17 and 27 days in vitro. The neuronal cultures were subjected to 15 min RF exposures at SAR of 1, 3, and 28 W/kg. At SAR close to the guidelines (1 and 3 W/kg), we found no conclusive evidence that 3.5 GHz RF exposure impacts the activity of neurons in vitro. On the contrary, CW and 5G-modulated signals elicited a clear decrease in bursting and total firing rates during RF exposure at high SAR levels (28 W/kg). Our experimental findings extend our previous results, showing that RF, at 1.8 to 3.5 GHz, inhibits the electrical activity of neurons in vitro at levels above environmental standards.