Effect of the Heaviness of Smoking Index (HSI) and Duration of Smoking on Central Neural Processing Using Brainstem Auditory Evoked Responses (BAERs).

Purpose of study The goal of this research was to find the correlation of nicotine dependence and duration of smoking with the status of central neuronal processing in chronic smokers. Our primary objective was to record brainstem auditory evoked responses (BAERs) in chronic smokers and further find their correlation to the Heaviness of Smoking Index (HSI) scores and years of non-abstained smoking of the subjects. We postulated that smoking leads to myelination abnormalities which in turn causes decreased impulse conduction velocity. Methods After obtaining informed consent, we conducted BAER on 60 male smokers who were further classified into groups based on their HSI scores (low, moderate, and high nicotine dependency) and 20 age-matched, non-smoking males. The obtained data was examined using the two-way ANOVA test and the Kruskal-Wallis test. Pearson's coefficient of correlation and the median (as a measure of central tendency) were calculated. Results We observed a non-significant negative correlation between wave I BAER latency and the degree of nicotine dependence. Wave II showed minimal correlation, whereas a positive correlation was seen in waves III, IV, and V. Interpeak latencies (IPL) I-III and III-V showed a non-significant positive correlation with the HSI score, whereas IPL I-V showed a significant positive correlation with the same. When correlated with the duration of smoking (years), the latencies (msec) of BAER waves I-V showed a pattern of progressively decreasing negative correlation, out of which waves I, II, and III were significantly affected. The IPL (msec) of waves I-III was non-significantly, yet positively, correlated, while the IPL of waves I-V and III-V showed a significant positive correlation to the duration of smoking. Conclusions The degree of nicotine dependence and duration of tobacco smoking progressively affected the latencies of BAER waves at the pontomedullary level of the brainstem. This indicates slower central neuronal processing at this level and an increased central transmission time, the extent of which is directly dependent on the extent of tobacco smoking. This is attributed to the myelination defects caused by direct and indirect effects of the toxic metabolites of tobacco smoke, chronic hypoxia, hypercapnia, and respiratory acidosis.

CTNND2 moderates the pace of synaptic maturation and links human evolution to synaptic neoteny.

Human-specific genes are potential drivers of brain evolution. Among them, SRGAP2C has contributed to the emergence of features characterizing human cortical synapses, including their extended period of maturation. SRGAP2C inhibits its ancestral copy, the postsynaptic protein SRGAP2A, but the synaptic molecular pathways differentially regulated in humans by SRGAP2 proteins remain largely unknown. Here, we identify CTNND2, a protein implicated in severe intellectual disability (ID) in Cri-du-Chat syndrome, as a major partner of SRGAP2. We demonstrate that CTNND2 slows synaptic maturation and promotes neuronal integrity. During postnatal development, CTNND2 moderates neuronal excitation and excitability. In adults, it supports synapse maintenance. While CTNND2 deficiency is deleterious and results in synaptic loss of SYNGAP1, another major ID-associated protein, the human-specific protein SRGAP2C, enhances CTNND2 synaptic accumulation in human neurons. Our findings suggest that CTNND2 regulation by SRGAP2C contributes to synaptic neoteny in humans and link human-specific and ID genes at the synapse.

Subjective visual sensitivity in neurotypical adults: insights from a magnetic resonance spectroscopy study.

Introduction: Altered subjective visual sensitivity manifests as feelings of discomfort or overload elicited by intense and irritative visual stimuli. This can result in a host of visual aberrations including visual distortions, elementary visual hallucinations and visceral responses like dizziness and nausea, collectively referred to as "pattern glare." Current knowledge of the underlying neural mechanisms has focused on overall excitability of the visual cortex, but the individual contribution of excitatory and inhibitory systems has not yet been quantified. Methods: In this study, we focus on the role of glutamate and γ-aminobutyric acid (GABA) as potential mediators of individual differences in subjective visual sensitivity, measured by a computerized Pattern Glare Test-a series of monochromatic square-wave gratings with three different spatial frequencies, while controlling for psychological variables related to sensory sensitivity with multiple questionnaires. Resting neurotransmitter concentrations in primary visual cortex (V1) and right anterior insula were studied in 160 healthy participants using magnetic resonance spectroscopy. Results: Data showed significant differences in the perception of visual distortions (VD) and comfort scores between men and women, with women generally reporting more VD, and therefore the modulatory effect of sex was considered in a further examination. A general linear model analysis showed a negative effect of occipital glutamate on a number of reported visual distortions, but also a significant role of several background psychological traits. When assessing comfort scores in women, an important intervening variable was the menstrual cycle. Discussion: Our findings do not support that baseline neurotransmitter levels have a significant role in overreactivity to aversive stimuli in neurotypical population. However, we demonstrated that biological sex can have a significant impact on subjective responses. Based on this additional finding, we suggest that future studies investigate aversive visual stimuli while examining the role of biological sex.

Somatosensory temporal discrimination analysis reveals impaired processing in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: While amyotrophic lateral sclerosis (ALS) is primarily characterized as a motor system disorder, there is a growing body of evidence indicating sensory involvement. This study aimed to examine the hypothesis that somatosensory processing is impaired in ALS. METHODS: Study participants were ALS patients followed at the Neuromuscular Outpatient Unit, as well as healthy volunteers, from March 2021 to July 2023. The Medical Research Council (MRC) sum score was calculated for nine muscle groups bilaterally. The clinical status of patients was evaluated with the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Penn Upper Motor Neuron core. Somatosensory temporal discrimination thresholds (STDTs) were recorded on the medial and lateral parts of both hands. Somatosensory cortex excitability was investigated with the paired somatosensory evoked potentials (SEP) paradigm in a subgroup. RESULTS: Increased STD values were detected in ALS patients compared to controls in both medial (107.66 ± 35 ms vs. 82.7 ± 32.5 ms, p = .001) and lateral (106.5 ± 34.5 ms vs. 82.9 ± 31.3 ms, p = .002) hands. There were no significant differences in STDTs among ALS patients across four regions (medial and lateral parts of the right and left hands). Amplitude ratios obtained from the paired-pulse SEP paradigm were approximately 1 for all interstimulus intervals (ISIs). STDTs did not show any correlations with motor findings or scales. DISCUSSION: Somatosensory processing appears to be compromised among ALS patients. The lack of correlation between impaired STDT and motor findings implies that it is a purely sensory deficit in ALS.

High temperature and hyperkalemia increase vulnerability of navaga cod (Eleginus nawaga) cardiomyocytes to the ecotoxicant 3-methyl-phenanthrene.

Oil and gas mining and transportation in the Arctic can lead to release of polycyclic aromatic hydrocarbons (PAHs) in the ocean and freshwater basins. PAHs are known for their toxic effects in fish hearts, including the inhibition of main ionic currents (IKr, INa and ICaL) in fish cardiac myocytes. The present study is the first one to assess the effect of a particular PAH abundant in crude oil and diesel, namely 3-methyl-phenanthrene (3-MP), on the electrical excitability (EE) of cardiomyocytes from navaga cod (Eleginus nawaga), commercial fish species from the Arctic. Action potentials (APs) were elicited in current-clamp experiments at 9, 15 and 21 °C, and AP characteristics and the current needed to elicit APs were examined. Also, the effects of 3 µM 3-MP were tested at 3 temperatures and in normal (3.5 mM) and high (8 mM) extracellular K+ concentrations. Elevation of temperature leads to hyperpolarization of resting membrane potential and AP shortening, but does not decrease EE. 3-MP was found to suppress EE in cardiomyocytes at 9 and 15 °C, but not at 21 °C. High extracellular K+ itself drastically decreases EE, although it does not worsen the effect of 3-MP. However, combination of hyperthermia and high K+ leads to augmentation of depressive effect of 3-MP on EE. We hypothesize that hyperthermia rescues Na+ channels from inactivation due to membrane hyperpolarization, thereby compensating for the partial inhibition of INa by 3-MP. However, elevation of extracellular K+ nullifies this protective mechanism by depolarizing the resting potential and aggravates the effect of 3-MP.

Regulation of voltage-gated sodium channels by TNF-α during herpes simplex virus latency establishment.

During lytic or latent infection of sensory neurons with herpes simplex virus type 1 (HSV-1) there are significant changes in the expression of voltage-gated Na+ channels, which may disrupt the transmission of pain information. HSV-1 infection can also evoke the secretion of various pro-inflammatory cytokines, including TNF-α and IL-6. In this work, we hypothesized that TNF-α regulates the expression of Na+ channels during HSV-1 latency establishment in ND7/23 sensory-like neurons. Latency establishment was mimicked by culturing HSV-1 infected ND7/23 cells in the presence of acyclovir (ACV) for 3 days. Changes in the functional expression of voltage-gated Na+ channels were assessed by whole-cell recordings. Our results demonstrate that infection of ND7/23 cells with the HSV-1 strain McKrae with GFP expression (M-GFP) causes a significant decrease in sodium currents during latency establishment. Exposure of ND7/23 cells to TNF-α during latency establishment reverses the effect of HSV-1, resulting in a significant increase in sodium current density. However, Na+ currents were not restored by 3 day-treatment with IL-6. There were no changes in the pharmacological and biophysical properties of sodium currents promoted by TNF-α, including sensitivity to tetrodotoxin and the current-voltage relationship. TNF-α stimulation of ND7/23 cells increases p38 signaling. Inhibition of p38 signaling with SB203580 or SB202190 eliminates the stimulatory effect of TNF-α on sodium currents. These results indicate that TNF-α signaling in sensory neurons during latency establishment upregulates the expression of voltage-gated Na+ channels in order to maintain the transmission of pain information.

Neuromuscular characteristics of eccentric, concentric and isometric contractions of the knee extensors.

PURPOSE: We compared voluntary drive and corticospinal responses during eccentric (ECC), isometric (ISOM) and concentric (CON) muscle contractions to shed light on neurophysiological mechanisms underpinning the lower voluntary drive in a greater force production in ECC than other contractions. METHODS: Sixteen participants (20-33 years) performed ISOM and isokinetic (30°/s) CON and ECC knee extensor contractions (110°-40° knee flexion) in which electromyographic activity (EMG) was recorded from vastus lateralis. Voluntary activation (VA) was measured during ISOM, CON and ECC maximal voluntary contractions (MVCs). Transcranial magnetic stimulation elicited motor-evoked potentials (MEPs) and corticospinal silent periods (CSP) during MVCs and submaximal (30%) contractions, and short-interval intracortical inhibition (SICI) in submaximal contractions. RESULTS: MVC torque was greater (P < 0.01) during ECC (302.6 ± 90.0 Nm) than ISOM (269.8 ± 81.5 Nm) and CON (235.4 ± 78.6 Nm), but VA was lower (P < 0.01) for ECC (68.4 ± 14.9%) than ISOM (78.3 ± 13.1%) and CON (80.7 ± 15.4%). In addition, EMG/torque was lower (P < 0.02) for ECC (1.9 ± 1.1 µV.Nm-1) than ISOM (2.2 ± 1.2 µV.Nm-1) and CON (2.7 ± 1.6 µV.Nm-1), CSP was shorter (p < 0.04) for ECC (0.097 ± 0.03 s) than ISOM (0.109 ± 0.02 s) and CON (0.109 ± 0.03 s), and MEP amplitude was lower (P < 0.01) for ECC (3.46 ± 1.67 mV) than ISOM (4.21 ± 2.33 mV) and CON (4.01 ± 2.06 mV). Similar results were found for EMG/torque and CSP during 30% contractions, but MEP and SICI showed no differences among contractions (p > 0.05). CONCLUSIONS: The lower voluntary drive indicated by reduced VA during ECC may be partly explained by lower corticospinal excitability, while the shorter CSP may reflect extra muscle spindle excitation of the motoneurons from vastus lateralis muscle lengthening.

The multi-stage plasticity in the aggression circuit underlying the winner effect.

Winning increases the readiness to attack and the probability of winning, a widespread phenomenon known as the "winner effect." Here, we reveal a transition from target-specific to generalized aggression enhancement over 10 days of winning in male mice. This behavioral change is supported by three causally linked plasticity events in the ventrolateral part of the ventromedial hypothalamus (VMHvl), a critical node for aggression. Over 10 days of winning, VMHvl cells experience monotonic potentiation of long-range excitatory inputs, transient local connectivity strengthening, and a delayed excitability increase. Optogenetically coactivating the posterior amygdala (PA) terminals and VMHvl cells potentiates the PA-VMHvl pathway and triggers the same cascade of plasticity events observed during repeated winning. Optogenetically blocking PA-VMHvl synaptic potentiation eliminates all winning-induced plasticity. These results reveal the complex Hebbian synaptic and excitability plasticity in the aggression circuit during winning, ultimately leading to increased "aggressiveness" in repeated winners.

Repetitive peripheral magnetic stimulation alone or in combination with repetitive transcranial magnetic stimulation in poststroke rehabilitation: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to comprehensively review the effects of repetitive peripheral magnetic stimulation (rPMS) alone or in combination with repetitive transcranial magnetic stimulation (rTMS) on improving upper limb motor functions and activities of daily living (ADL) in patients with stroke, and to explore possible efficacy-related modulators. METHODS: A literature search from 1st January 2004 to 1st June 2024 was performed to identified studies that investigated the effects of rPMS on upper limb motor functions and ADL in poststroke patients. RESULTS: Seventeen studies were included. Compared with the control, both rPMS alone or rPMS in combination with rTMS significantly improved upper limb motor function (rPMS: Hedge's g = 0.703, p = 0.015; rPMS + rTMS: Hedge's g = 0.892, p < 0.001) and ADL (rPMS: Hedge's g = 0.923, p = 0.013; rPMS + rTMS: Hedge's g = 0.923, p < 0.001). However, rPMS combined with rTMS was not superior to rTMS alone on improving poststroke upper limb motor function and ADL (Hedge's g = 0.273, p = 0.123). Meta-regression revealed that the total pulses (p = 0.003) and the number of pulses per session of rPMS (p < 0.001) correlated with the effect sizes of ADL. CONCLUSIONS: Using rPMS alone or in combination with rTMS appears to effectively improve upper extremity functional recovery and activity independence in patients after stroke. However, a simple combination of these two interventions may not produce additive benefits than the use of rTMS alone. Optimization of rPMS protocols, such as applying appropriate dosage, may lead to a more favourable recovery outcome in poststroke rehabilitation.

Induction of long-term hyperexcitability by memory-related cAMP signaling in isolated nociceptor cell bodies.

Persistent hyperactivity of nociceptors is known to contribute significantly to long-lasting sensitization and ongoing pain in many clinical conditions. It is often assumed that nociceptor hyperactivity is mainly driven by continuing stimulation from inflammatory mediators. We have tested an additional possibility: that persistent increases in excitability promoting hyperactivity can be induced by a prototypical cellular signaling pathway long known to induce late-phase long-term potentiation (LTP) of synapses in brain regions involved in memory formation. This cAMP-PKA-CREB-gene transcription-protein synthesis pathway was tested using whole-cell current clamp methods on small dissociated sensory neurons (primarily nociceptors) from dorsal root ganglia (DRGs) excised from previously uninjured ("naïve") male rats. Six-hour treatment with the specific Gαs-coupled 5-HT4 receptor agonist, prucalopride, or with the adenylyl cyclase activator forskolin induced long-term hyperexcitability (LTH) in DRG neurons that manifested 12-24 h later as action potential (AP) discharge (ongoing activity, OA) during artificial depolarization to -45 mV, a membrane potential that is normally subthreshold for AP generation. Prucalopride treatment also induced significant long-lasting depolarization of resting membrane potential (from -69 to -66 mV), enhanced depolarizing spontaneous fluctuations (DSFs) of membrane potential, and produced trends for reduced AP threshold and rheobase. LTH was prevented by co-treatment of prucalopride with inhibitors of PKA, CREB, gene transcription, or protein synthesis. As in the induction of synaptic memory, many other cellular signals are likely to be involved. However, the discovery that this prototypical memory induction pathway can induce nociceptor LTH, along with reports that cAMP signaling and CREB activity in DRGs can induce hyperalgesic priming, suggest that early, temporary, cAMP-induced transcriptional and translational mechanisms can induce nociceptor LTH that might last for long periods. The present results also raise the question of whether reactivation of primed signaling mechanisms by re-exposure to inflammatory mediators linked to cAMP synthesis during subsequent challenges to bodily integrity can "reconsolidate" nociceptor memory, extending the duration of persistent hyperexcitability.

Effects of physical training combined with transcranial direct current stimulation on maximal strength and lower limb explosive strength in healthy adults.

Objective: The purpose of this systematic review and meta-analysis was to investigates whether transcranial direct current stimulation applied during physical training increases muscle strength in comparison with sham tDCS combined with physical training. Methods: Randomized controlled trials of the effects of tDCS combined physical training intervention on muscle strength and cortical excitability were collected by searching Web of Science, Pubmed, EBSCO, CNKI. The retrieval date ends in April 2024. 11 randomized controlled trials are finally included. The total sample size of the study is 338. The experimental group was subjected to tDCS combined with physical training intervention, and the control group was physical training combined with sham tDCS intervention. Results: There is a significant increase in maximal strength (SMD = 0.38; 95% CI: 0.09, 0.67; p = 0.01) and lower limb explosive strength (MD = 2.90; 95% CI: 1.06, 4.74; p = 0.002) when physical training was performed with tDCS, but not following physical training combined with sham tDCS. Subgroup analysis of the subject population showed an increase in muscle strength in those with training experience following tDCS combined with physical training (SMD = 0.39; 95% CI: 0.08, 0.70; p = 0.01), but not for those without training experience (SMD = 0.29; 95% CI: -0.06, 0.63; p = 0.10). Motor evoked potential (MEP) wave amplitude increased significantly following physical training with tDCS (SMD = 0.71; 95% CI: 0.18, 1.24; p = 0.008), but was not different between groups (SMD = 0.16; 95% CI: -0.33, 0.65; p = 0.52). Conclusions: tDCS combined with physical training intervention can improve muscle strength, lower limb explosive strength and cerebral cortex excitability. Compared to tDCS combined with training of small muscle groups, tDCS combined with training of large muscle groups was more effective in improving muscle strength. Muscle strength was more likely to improve after tDCS combined with physical training in people with physical training experience compared with people without physical training experience. The combination of tDCS with physical training intervention and the sham-tDCS with physical training intervention both increased cortical excitability. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO, identifier (CRD42024550454).

Impact of background input on memory consolidation.

Memory consolidation involves repeated replay of new information by the hippocampus, which transfers memories to the neocortex for long-term storage. This occurs mainly during slow wave sleep, a phase characterized in the cortex by low cholinergic tone and low afferent input. High cholinergic tone has been shown to hamper memory consolidation, probably mediated by reduced network excitability (the ease of activity propagation in a network). We used cortical neuronal networks on multi electrode arrays to investigate whether low background input contributes to memory consolidation. Networks received focal electrical stimuli to memorize, with or without background afferent input (global optogenetic stimulation). Background stimulation hampered memory formation and consolidation, confirming the importance of low background input. Moreover, it lowered network excitability, similar to high cholinergic tone. These findings suggest that high network excitability is a critical feature of slow wave sleep that facilitates memory consolidation.

Investigating the effects of excitatory and inhibitory somatosensory rTMS on somatosensory functioning in the acute and subacute phases of stroke: a preliminary double-blind and randomized trial.

Background: Repetitive transcranial magnetic stimulation (rTMS) targeting the primary somatosensory cortex (S1) has a potential effect on somatosensory functioning following a stroke. However, S1-rTMS was combined with peripheral therapies in previous trials. Moreover, these studies have commonly targeted the ipsilesional S1 with excitatory rTMS paradigms. Methods: This double-blind, randomized trial (registration number: ChiCTR2200059098) investigated two forms of paradigms, that is ipsilesional excitatory and contralesional inhibitory rTMS, as a stand-alone treatment in post-stroke somatosensation. Patients in the acute and subacute phases of stroke were randomly assigned to either contralesional 1-Hz or ipsilesional 10-Hz rTMS group and received 10 daily sessions of treatment in two consecutive weeks. Results: Results indicate that the contralesional inhibitory and ipsilesional excitatory stimulation were equally effective in improving somatosensory functioning. Moreover, this effect was most prominent in deep sensations and subjective sensations. Using single-pulse EMG recordings, our data also revealed an increased MEP amplitude in the ipsilesional motor cortex following ipsilesional excitatory treatment. Conclusion: This preliminary study demonstrates the primary somatosensory cortex as an effective rTMS target in somatosensory recovery following stroke. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=166474, ChiCTR2200059098.

Effect of home-based transcranial direct current stimulation combined with nutritional counseling therapy on binge eating disorder symptoms: A randomized pilot trial.

OBJECTIVE: To examine the effect of nutritional counseling therapy (NCT) combined with transcranial direct current stimulation (tDCS) on Binge Eating Disorder (BED) symptoms. METHODS: 40 women with BED were randomly (ratio of 2:2:2) allocated to one of the groups: active tDCS (a-tDCS), NCT, sham tDCS (s-tDCS) with NCT, and a-tDCS with NCT. Home-based tDCS was applied to the dorsolateral prefrontal cortex for 28 sessions. RESULTS: A mixed analysis of variance showed no main effect between groups or a time × group interaction. However, a significant main effect was found for time on the primary outcome: Binge Eating Scale (p = 0.001; eta2p= 0.325), which tended to decrease during treatment and follow-up. A significant main effect was found on the secondary outcome: short-interval intracortical inhibition (SICI) (p = 0.02; eta2p= 0.112), a measure of inhibitory function, which increased from baseline to the final period in the a-tDCS group, without significant differences between groups. CONCLUSIONS: These findings reveal that the combined therapy did not have a synergic effect on BED symptoms. Since this is a pilot study and this is a promising area, we provide data to plan future larger-scale studies investigating the effects of tDCS and behavioral interventions in BED treatment.

1H-MRS reveals abnormal energy metabolism and excitatory-inhibitory imbalance in a chronic migraine-like state induced by nitroglycerin in mice.

BACKGROUND: Chronic migraine is closely related to the dysregulation of neurochemical substances in the brain, with metabolic imbalance being one of the proposed causes of chronic migraine. This study aims to evaluate the metabolic changes between energy metabolism and excitatory and inhibitory neurotransmitters in key brain regions of mice with chronic migraine-like state and to uncover the dysfunctional pathways of migraine. METHODS: A chronic migraine-like state mouse model was established by repeated administration of nitroglycerin (NTG). We used von Frey filaments to assess the mechanical thresholds of the hind paw and periorbital in wild-type and familial hemiplegic migraine type 2 mice. After the experiments, tissue was collected from five brain regions: the somatosensory cortex (SSP), hippocampus, thalamus (TH), hypothalamus, and the spinal trigeminal nucleus caudalis (TNC). Proton magnetic resonance spectroscopy (1H-MRS) was employed to study the changes in brain metabolites associated with migraine, aiming to explore the mechanisms underlying metabolic imbalance in chronic migraine-like state. RESULTS: In NTG-induced chronic migraine-like state model, we observed a significant reduction in energy metabolism during central sensitization, an increase in excitatory neurotransmitters such as glutamate, and a tendency for inhibitory neurotransmitters like GABA to decrease. The TNC and thalamus were the most affected regions. Furthermore, the consistency of N-acetylaspartate levels highlighted the importance of the TNC-TH-SSP pathway in the ascending nociceptive transmission of migraine. CONCLUSION: Abnormal energy metabolism and neurotransmitter imbalance in the brain region of NTG-induced chronic migraine-like state model are crucial mechanisms contributing to the chronicity of migraine.

Transcranial direct current stimulation as a potential remyelinating therapy: Visual evoked potentials recovery in cuprizone demyelination.

AIMS: Non-invasive neuromodulation by transcranial direct current stimulation (tDCS), owing to its reported beneficial effects on neuronal plasticity, has been proposed as a treatment to promote functional recovery in several neurological conditions, including demyelinating diseases like multiple sclerosis. Less information is available on the effects of tDCS in major pathological mechanisms of multiple sclerosis, such as demyelination and inflammation. To learn more about the latter effects, we applied multi-session anodal tDCS in mice exposed to long-term cuprizone (CPZ) diet, known to induce chronic demyelination. METHODS: Visual evoked potentials (VEP) and motor performance (beam test) were employed for longitudinal monitoring of visual and motor pathways in 28 mice undergoing CPZ diet, compared with 12 control (H) mice. After randomization, anodal tDCS was applied for 5 days in awake, freely-moving surviving animals: 12 CPZ-anodal, 10 CPZ-sham, 5H-anodal, 5 h-sham. At the end of the experiment, histological analysis was performed on the optic nerves and corpus callosum for myelin, axons and microglia/macrophages. KEY FINDINGS: CPZ diet was associated with significantly delayed VEPs starting at 4 weeks compared with their baseline, significant compared with controls at 8 weeks. After 5-day tDCS, VEPs latency significantly recovered in the active group compared with the sham group. Similar findings were observed in the time to cross on the beam test Optic nerve histology revealed higher myelin content and lower microglia/macrophage counts in the CPZ-Anodal group compared with CPZ-Sham. SIGNIFICANCE: Multiple sessions of anodal transcranial direct current stimulation (tDCS) in freely moving mice induced recovery of visual nervous conduction and significant beneficial effects in myelin content and inflammatory cells in the cuprizone model of demyelination. Altogether, these promising findings prompt further exploration of tDCS as a potential therapeutic approach for remyelination.

A comprehensive review of electrophysiological techniques in amyotrophic lateral sclerosis research.

Amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is characterized by progressive motor neuron degeneration, leading to widespread weakness and respiratory failure. While a variety of mechanisms have been proposed as causes of this disease, a full understanding remains elusive. Electrophysiological alterations, including increased motor axon excitability, likely play an important role in disease progression. There remains a critical need for non-animal disease models that can integrate electrophysiological tools to better understand underlying mechanisms, track disease progression, and evaluate potential therapeutic interventions. This review explores the integration of electrophysiological technologies with ALS disease models. It covers cellular and clinical electrophysiological tools and their applications in ALS research. Additionally, we examine conventional animal models and highlight advancements in humanized models and 3D organoid technologies. By bridging the gap between these models, we aim to enhance our understanding of ALS pathogenesis and facilitate the development of new therapeutic strategies.

The impact of acute blood-flow-restriction resistance exercise on somatosensory-evoked potentials in healthy adults.

Blood-flow-restriction exercise (BFREX) is an emerging method to stimulate hypertrophy and strength without the need for high training loads. However, the impact of BFREX concerning somatosensory processing remains elusive. Here, we aimed to investigate the acute effects of BFREX on somatosensory processing in healthy adults using somatosensory-evoked potentials (SEPs). Twelve healthy adults (23.0 ± 3.2 years of age) participated in a randomized crossover experiment, consisting of three experimental conditions: application of blood-flow restriction without resistance exercise (BFR), resistance exercise for multiple sets with blood-flow restriction (BFREX) and traditional resistance exercise (unilateral biceps curls) for multiple sets without BFR (EX). SEP measurements were recorded bilaterally before, during and after each condition. SEP amplitudes were largely unaffected during various occlusive conditions. Nonetheless, our findings demonstrate a significant decrease in N9 latencies for condition EX compared with BFR, specifically in the exercised limb (mean difference = -0.26 ms, SE = 0.06 ms, P = 0.002, d = -0.335). This study provides evidence on the lack of impact of BFREX within the somatosensory domain, according to current guidelines. As an alternative method to traditional high-load resistance exercise, BFREX might offer a considerable upside for rehabilitative settings by reducing strain on the musculoskeletal system.

Virtual stimulation of the interictal EEG network localizes the EZ as a measure of cortical excitability.

Introduction: For patients with drug-resistant epilepsy, successful localization and surgical treatment of the epileptogenic zone (EZ) can bring seizure freedom. However, surgical success rates vary widely because there are currently no clinically validated biomarkers of the EZ. Highly epileptogenic regions often display increased levels of cortical excitability, which can be probed using single-pulse electrical stimulation (SPES), where brief pulses of electrical current are delivered to brain tissue. It has been shown that high-amplitude responses to SPES can localize EZ regions, indicating a decreased threshold of excitability. However, performing extensive SPES in the epilepsy monitoring unit (EMU) is time-consuming. Thus, we built patient-specific in silico dynamical network models from interictal intracranial EEG (iEEG) to test whether virtual stimulation could reveal information about the underlying network to identify highly excitable brain regions similar to physical stimulation of the brain. Methods: We performed virtual stimulation in 69 patients that were evaluated at five centers and assessed for clinical outcome 1 year post surgery. We further investigated differences in observed SPES iEEG responses of 14 patients stratified by surgical outcome. Results: Clinically-labeled EZ cortical regions exhibited higher excitability from virtual stimulation than non-EZ regions with most significant differences in successful patients and little difference in failure patients. These trends were also observed in responses to extensive SPES performed in the EMU. Finally, when excitability was used to predict whether a channel is in the EZ or not, the classifier achieved an accuracy of 91%. Discussion: This study demonstrates how excitability determined via virtual stimulation can capture valuable information about the EZ from interictal intracranial EEG.

The value of electrophysiological testing in the adjunctive diagnosis of premature ejaculation.

BACKGROUND: Although the four-class system of classifying premature ejaculation (PE), including lifelong PE (LPE), acquired PE (APE), natural variable PE (NPE), and subjective PE (SPE), has existed for many years, objective classification standards in clinical practice are lacking. AIM: In this study, we sought to investigate the use of electrophysiologic parameters to assist in the classification of PE, thereby guiding subsequent treatment. METHODS: From July 2023 to April 2024, 187 study participants were enrolled. For each participant, the biological sensory threshold (BST), penile sympathetic skin response (PSSR), and dorsal nerve somatosensory evoked potential (DNSEP) were recorded. OUTCOMES: The differences in the PSSR latencies (PL) and DNSEP latencies (DL), the PSSR amplitudes (PA) and DNSEP amplitudes (DA), and the BST were compared among the LPE, APE, SPE, NPE, and healthy control (HC) groups. RESULTS: The participants were divided into the LPE (46 cases), APE (53 cases), SPE (20 cases), NPE (33 cases), and HC (35 cases) groups. The results showed shorter latencies of the PSSR (PL) and DNSEP (DL), larger amplitudes of the PSSR (PA) and DNSEP (DL), and smaller BST in the LPE group than in the NPE, SPE, APE, and HC groups (P < .05). In addition, the larger PA and shorter PL in the APE group than in the NPE and HC groups (P < .05). However, the electrophysiological parameters were not significantly different among the NPE, SPE, and HC groups (P > .05). In addition, PL <1262.0 milliseconds and DL <41.85 milliseconds were strong predictors of LPE, 1262.0 milliseconds < PL <1430.0 milliseconds was a predictor of APE, and PL >1430.0 milliseconds suggested possible SPE or NPE. CLINICAL IMPLICATIONS: Analysis of the electrophysiological parameters of PE may be helpful for classification and treatment. STRENGTHS AND LIMITATIONS: No previous study, to our knowledge, has analyzed the electrophysiological parameters of the four types of PE. The main limitation is the small sample size. CONCLUSION: APE is characterized by increased sympathetic excitability, whereas LPE is characterized by increased penile sensitivity and increased sympathetic excitability. However, penile sensitivity and sympathetic excitability in SPE and NPE patients may not differ significantly from normal.