Human cortical activity reflects interactions between local recurrent circuits and distributed brain-wide inputs, but how these contributions shape cortical dynamics remains unclear. We compared oscillatory and single unit activity in laminar recordings from the same human cortical regions in eight patients across wakefulness, NREM sleep, and acute slices after surgical isolation. Gamma-band spike-field synchronization increased from wakefulness to sleep and isolated cortex, whereas population coupling, putative connectivity, network integration, and dynamical dimensionality declined. Laminar gamma sink-source organization persisted in isolation, indicating the presence of local gamma-generating mechanisms. Integration with histological data showed preserved tissue architecture, while neuronal density predicted population integration in vivo but not after isolation. Removing long-range inputs thus did not suppress cortical activity but shifted its organization toward stronger rhythmic coordination and reduced integration. Our findings suggest that neocortical microcircuits intrinsically generate coherent gamma activity, whereas network embedding supports the diverse, high-dimensional dynamics of the intact cortex.

The subthalamic nucleus (STN) is a critical hub for inhibitory control, implicated in decision making under conflict and impulsivity. Delta frequency oscillations have also been associated with inhibitory control processes, yet the relationship between human STN neuronal activity and local delta frequencies during response inhibition remains unresolved. Here we recorded STN neurons and local field potentials in patients with Parkinson's disease performing a stop-signal reaction time task during deep brain stimulation surgery. Approximately half of STN neurons responded to a diverse set of behaviorally relevant events including go and stop signals, with stronger go-related firing and enhanced delta phase coupling linked to failed inhibition. Notably, a specific population of bursting STN neurons showed increased delta coupling. These findings suggest that STN neurons integrate go and stop information, and that enhanced delta engagement and bursting may impair inhibitory control, providing insights into the neuronal mechanism of action cancellation.

Rising global temperatures can lead to heat waves, which in turn can pose health risks to the community. However, a notable gap remains in highlighting the primary contributing factors that amplify heat-health risk among vulnerable populations. This study aims to evaluate the precedence of heat stress contributing factors in urban and rural vulnerable populations living in hot and humid tropical regions. A comparative cross-sectional study was conducted, involving 108 respondents from urban and rural areas in Klang Valley, Malaysia, using a face-to-face interview and a validated questionnaire. Data was analyzed using the principal component analysis, categorizing factors into exposure, sensitivity, and adaptive capacity indicators. In urban areas, five principal components (PCs) explained 64.3% of variability, with primary factors being sensitivity (health morbidity, medicine intake, increased age), adaptive capacity (outdoor occupation type, lack of ceiling, longer residency duration), and exposure (lower ceiling height, increased building age). In rural, five PCs explained 71.5% of variability, with primary factors being exposure (lack of ceiling, high thermal conductivity roof material, increased building age, shorter residency duration), sensitivity (health morbidity, medicine intake, increased age), and adaptive capacity (female, non-smoking, higher BMI). The order of heat-health vulnerability indicators was sensitivity > adaptive capacity > exposure for urban areas, and exposure > sensitivity > adaptive capacity for rural areas. This study demonstrated a different pattern of leading contributors to heat stress between urban and rural vulnerable populations.

Epilepsy is a prevalent neurological condition, with underlying neuronal mechanisms involving hyperexcitability and hypersynchrony. Imbalance between excitatory and inhibitory circuits, as well as histological reorganization are relatively well-documented in animal models or even in the human hippocampus, but less is known about human neocortical epileptic activity. Our knowledge about changes in the excitatory signaling is especially scarce, compared to that about the inhibitory cell population. This study investigated the firing properties of single neurons in the human neocortex in vitro, during pharmacological blockade of glutamate receptors, and additionally evaluated anatomical changes in the excitatory circuit in tissue samples from epileptic and non-epileptic patients. Both epileptic and non-epileptic tissues exhibited spontaneous population activity (SPA), NMDA receptor antagonization reduced SPA recurrence only in epileptic tissue, whereas further blockade of AMPA/kainate receptors reversibly abolished SPA emergence regardless of epilepsy. Firing rates did not significantly change in excitatory principal cells and inhibitory interneurons during pharmacological experiments. Granular layer (L4) neurons showed an increased firing rate in epileptic compared to non-epileptic tissue. The burstiness of neurons remained unchanged, except for that of inhibitory cells in epileptic recordings, which decreased during blockade of glutamate receptors. Crosscorrelograms computed from single neuron discharge revealed both mono- and polysynaptic connections, particularly involving intrinsically bursting principal cells. Histological investigations found similar densities of SMI-32-immunopositive long-range projecting pyramidal cells in both groups, and shorter excitatory synaptic active zones with a higher proportion of perforated synapses in the epileptic group. These findings provide insights into epileptic modifications from the perspective of the excitatory system and highlight discrete alterations in firing patterns and synaptic structure. Our data suggest that NMDA-dependent glutamatergic signaling, as well as the excitatory synaptic machinery are perturbed in epilepsy, which might contribute to epileptic activity in the human neocortex.

Knowledge about the activity of single neurons is essential in understanding the mechanisms of synchrony generation, and particularly interesting if related to pathological conditions. The generation of interictal spikes-the hypersynchronous events between seizures-is linked to hyperexcitability and to bursting behaviour of neurons in animal models. To explore its cellular mechanisms in humans we investigated the activity of clustered single neurons in a human in vitro model generating both physiological and epileptiform synchronous events. We show that non-epileptic synchronous events resulted from the finely balanced firing of excitatory and inhibitory cells, which was shifted towards an enhanced excitability in epileptic tissue. In contrast, interictal-like spikes were characterised by an asymmetric overall neuronal discharge initiated by excitatory neurons with the presumptive leading role of bursting pyramidal cells, and possibly terminated by inhibitory interneurons. We found that the overall burstiness of human neocortical neurons is not necessarily related to epilepsy, but the bursting behaviour of excitatory cells comprising both intrinsic and synaptically driven bursting is clearly linked to the generation of epileptiform synchrony.

Purpose: We aimed to examine the effectiveness of different therapeutic options for and to identify the possible risk factors of recurrent internal carotid artery (ICA) in-stent restenosis (ISR). Methods: Forty-six ICA ISRs, which were reintervened at least once, were retrospectively analyzed regarding clinical and imaging characteristics, as well as invasive treatment type (percutaneous transluminal angioplasty [PTA] with a plain balloon, PTA with a drug-eluting balloon [DEB], re-stenting) used. Results: The median follow-up was 29.5 months (IQR, 8.5-52.8 months) in patients who underwent reintervention for ICA ISR. Stent occlusion occurred in 3 patients (6.5%). One ISR recurrence was noted in 10 patients (21.7%); reintervention was carried out in 7 cases (7/10 [70%]; PTA, N = 5; PTA with a DEB, N = 1; re-stenting, N = 1), while 3 patients (3/10; 30%) received best medical treatment. Two ISR recurrences were observed in 3 patients (6.5%); all of them underwent reintervention (PTA, N = 1; PTA with a DEB, N = 2). Three ISR recurrences were seen in 1 patient (2.2%), who was treated with PTA. No recurrence was observed in those patients, who had DEB treatment. Multiple logistic regression analysis revealed statin therapy to be a protective factor against recurrent ISR (OR, 0.17; 95% CI, 0.03-0.84; P = .029). Conclusion: Our study suggests that PTA with a DEB is the most effective for the treatment of recurrent ISR, and confirms the importance of statin use in patients who have had a carotid reintervention.

Összefoglaló. Az aortadissectio krónikus stádiumában kialakuló thoracoabdominalis tágulatok megoldása multidiszciplináris megközelítést, nagy felkészültséget és fejlett technológiát igényel. A jellemzően többlépcsős műtétsorozat mortalitása és morbiditása az endovascularis technológia fejlődésével csökkent, de még mindig jelentős. A fenesztrált endovascularis aortaműtét a thoracoabdominalis nyitott műtét alternatívája, mely kisebb mortalitással és morbiditással, rövidebb kórházi tartózkodással jár. Aortadissectio esetén történő alkalmazása az aorta lumenében lévő membrán miatt kihívást jelent. Esetbemutatásunkban egy 56 éves nőbeteget demonstrálunk, aki tíz évvel korábban A-típusú dissectio miatt aorta ascendens rekonstrukción esett át. A követés során csaknem a teljes aorta tágulata alakult ki, melynek megoldása három lépésben történt. Az első lépésben a disszekált aortaív nyitott műtétjét végeztük 'frozen elephant trunk' technikával, majd az aorta descendens tágulatának endovascularis kezelése történt sztentgraft-implantációval. A műtétsorozat záró lépése egy fenesztrált endovascularis aortaműtét volt, mely egyben ezen technikának az aortadissectio esetében történt első hazai alkalmazását jelenti. Orv Hetil. 2021; 162(31): 1260-1264. Summary. Thoracoabdominal aortic aneurysms developing in the chronic phase of an aortic dissection require multidisciplinary approach, experienced operators and advanced technology. The mortality and morbidity rate of these multistage operations were reduced with the latest technical achievements in endovascular repair, but they are still significant. Fenestrated endovascular aortic repair, an alternative of thoracoabdominal open repair, is associated with less mortality and morbidity, shorter hospital stay. Using fenestrated devices in aortic dissection is usually technically demanding due to the dissection membrane. We report the case of a 56-year-old woman, who underwent ascending aortic repair due to type A aortic dissection. During the follow-up, a large thoracoabdominal aneurysm developed involving also the arch. We performed a three-stage operation starting with the open repair of the aortic arch using a 'frozen elephant trunk' device followed by a thoracic endovascular aortic repair of the descending aorta. The final stage was a fenestrated endovascular aortic repair, which is the first use of this technique in aortic dissection in Hungary. Orv Hetil. 2021; 162(31): 1260-1264.

Background: Cardiovascular diseases are the number one cause of death globally and represent 31% of all global deaths. The aim of our study was to determine the influence of front effects on acute cardiovascular diseases (ACVDs). Methods: We obtained all ACVD admissions in a Central-European region, Hungary, Budapest. A timeseries analysis was applied to 6499 morbidity cases during a five-year period (2009-2013). Poissonregression model was used and adjusted for air temperature, pressure, humidity, wind velocity, their interactions and seasonality to assess the association of fronts and ACVDs. Results: There is a positive significant association between ACVDs and a cold front effect lagged by one day (p = 0.018) with a relative risk (RR) of 1.095 [95% CI (1.021,1.181)]. Our findings show that among patient subgroups with major cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, history of CVDs) the patterns are similar, but occluded fronts also have a significant effect. Conclusion: Atmospheric fronts could play an important role in the pathogenesis of ACVDs. Our findings might help to provide a better understanding about fronts as minor cardiovascular risk factors and to organize medical prevention more effectively. Our research project may become a basis of a new field of preventive cardiovascular medicine in the future. (C) 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

The correct practice is the one that is proven to be the most effective based on systematic statistical analyses of different treatment methods, and is applied according to evidence-based principles. In recent years, not only has the European Society of Vascular Surgery created a guideline about the management of supra-aortic steno-occlusive disease, but some nations' vascular surgical societies and related disciplines have also developed their own guidance. In this paper, the guidelines by the European societies on the clinical care of patients with carotid artery luminal narrowing is compared to national guidelines published in Hungarian, English, German, and Italian. Although the fundamental points of the guidelines are similar, there are some important differences among them both in presentation and in content; as a result, they sometimes appear to be contradictory. The three main sources of inconsistency are the various goals, the discrepancy in the definition of symptomatic and asymptomatic carotid artery stenosis, and the bias arising from the use of distinct evidence levels. A comparison of guidelines suggests that the treatment of symptomatic significant carotid artery stenosis with surgery can be considered evidence. Symptomatic carotid artery stenosis is defined as transient or definite plegia, paresis, aphasia due to cerebral ischemia, and monocular blindness caused by embolism in the central retinal artery. However, in the case of asymptomatic 70% or greater carotid artery stenosis, the guidelines are quite heterogeneous, and these patients require individual consideration and a vascular team decision is recommended.

Összefoglaló. A tudomány jelenlegi állása szerint – csoportok összehasonlítására épülő matematikai-statisztikai eszközökkel – a leginkább hatékonynak és hatásosnak vélt kezelési módszerek szisztematikus elemzése mentén, a bizonyítékokon alapuló irányelveken nyugvó gyógyító munkát tekintjük követendőnek. A nyaki verőérszűkület ellátása esetén az utóbbi években elkészült mind a hazai, mind az európai irányelv, mindemellett a társszakmák irányelveiben is megjelentek kezelési javaslatok. Közleményünkben összehasonlítottuk a témában publikált magyar, angol, német és olasz nyelvű, valamint az európai társaságok által kiadott irányelveket. Az irányelvek alapelveikben hasonlóak, formailag és tartalmilag azonban jelentős (időnként egymásnak ellentmondani látszó) különbségeket találhatunk. Az ellentmondások három leggyakoribb oka: 1) az egyes irányelvek által kitűzött célok különbözősége, 2) az aszimptomatikus és szimptomatikus betegcsoport definíciói, valamint 3) az eltérő evidenciaszintek. Az irányelvek összevetése alapján a tünetes, szignifikáns nyaki verőérszűkületek sebészi ellátása evidenciának tekinthető. A szimptomatikus nyaki verőérszűkület a definíció szerint ellenoldali cerebralis ischaemia okozta, tranziens vagy definitív plegia, paresis, aphasia és az azonos oldali arteria centralis retinae embolisatiója miatti amaurosis fugax. A tünetmentes nyaki verőérszűkületek ellátása tekintetében az európai és a nemzeti irányelvek nem azonosak, ezen esetek terápiás döntése egyéni mérlegelést igényel. Tünetmentes, 70%-os stenosis esetén vascularteam-konzílium javasolt. Orv Hetil. 2020; 161(51): 2139–2145. Summary. The correct practice is the one that is proven to be the most effective based on systematic statistical analyses of different treatment methods, and is applied according to evidence-based principles. In recent years, not only has the European Society of Vascular Surgery created a guideline about the management of supra-aortic steno-occlusive disease, but some nations’ vascular surgical societies and related disciplines have also developed their own guidance. In this paper, the guidelines by the European societies on the clinical care of patients with carotid artery luminal narrowing is compared to national guidelines published in Hungarian, English, German, and Italian. Although the fundamental points of the guidelines are similar, there are some important differences among them both in presentation and in content; as a result, they sometimes appear to be contradictory. The three main sources of inconsistency are the various goals, the discrepancy in the definition of symptomatic and asymptomatic carotid artery stenosis, and the bias arising from the use of distinct evidence levels. A comparison of guidelines suggests that the treatment of symptomatic significant carotid artery stenosis with surgery can be considered evidence. Symptomatic carotid artery stenosis is defined as transient or definite plegia, paresis, aphasia due to cerebral ischemia, and monocular blindness caused by embolism in the central retinal artery. However, in the case of asymptomatic 70% or greater carotid artery stenosis, the guidelines are quite heterogeneous, and these patients require individual consideration and a vascular team decision is recommended. Orv Hetil. 2020; 161(51): 2139–2145.

Quantitative MRI methods have recently gained extensive interest and are seeing substantial developments; however, their application in single patient vs control group comparisons is often limited by inherent statistical difficulties. One such application is detecting malformations of cortical development (MCDs) behind drug resistant epilepsies, a task that, especially when based solely on conventional MR images, may represent a serious challenge. We aimed to develop a novel straightforward voxel-wise evaluation method based on the Mahalanobis-distance, combining quantitative MRI data into a multidimensional parameter space and detecting lesion voxels as outliers. Simulations with standard multivariate Gaussian distribution and resampled DTI-eigenvalue data of 45 healthy control subjects determined the optimal critical value, cluster size threshold, and the expectable lesion detection performance through ROC-analyses. To reduce the effect of false positives emanating from registration artefacts and gyrification differences, an automatic classification method was applied, fine-tuned using a leave-one-out strategy based on diffusion and T1-weighted data of the controls. DWI processing, including thorough corrections and robust tensor fitting was performed with ExploreDTI, spatial coregistration was achieved with the DARTEL tools of SPM12. Additional to simulations, clusters of outlying diffusion profile, concordant with neuroradiological evaluation and independent calculations with the MAP07 toolbox were identified in 12 cases of a 13 patient example population with various types of MCDs. The multidimensional approach proved sufficiently sensitive in pinpointing regions of abnormal tissue microstructure using DTI data both in simulations and in the heterogeneous example population. Inherent limitations posed by registration artefacts, age-related differences, and the different or mixed pathologies limit the generalization of specificity estimation. Nevertheless, the proposed statistical method may aid the everyday examination of individual subjects, ever so more upon extending the framework with quantitative information from other modalities, e.g. susceptibility mapping, relaxometry, or perfusion.

Introduction: According to the current clinical guidelines the indication for any intervention on carotid artery stenosis is a minimum 70% grade diameter stenosis. The perioperative risk of stroke of carotid artery endarterectomy is around 2%.Clinical decisions may be altered if any plaque features could be identified to be responsible for elevated risk of cerebral ischaemia. Currently, there is no imaging technique widely accepted and used clinically to predict potentially higher stroke risk. Our aim is the identification of plaque components on CTA images of patients with significant carotid artery stenosis. Furthermore, prediction of potentially increased risk of cerebral ischaemia caused by plaque instability based on the correlation of plaque components and relevant cerebral ischaemic lesions on preoperative head MRI. Methods: Asymptomatic and symptomatic patients with high grade carotid artery stenosis operated at Semmelweis University between 01.01.2016 and 30.05.2017 were enrolled to the study. Enrollment criteria were the preoperative protocolized CTA by Philips Brilliance iCT and the consent to the preoperative MRI. The CTA imaging of the plaques were analysed by Medis AngioQ software. The ratio of the different plaque components (fibrotic, fatty fibrotic, necrotic and calcified) to the total plaque volume were calculated. The cerebral ischemic lesions in MRI were classified by the Fazekas-scale (0-3). The statistical analysis was performed by SPSS software. Results: During the study period out of 471 operated patients 60 fulfilled all the enrollment criteria. In 60 cases the CTA plaque analysis and MRI Fazakas-scale classification were performed. There was a significant correlation (p=0.047) between the higher volume of necrotic component ratio and the higher incidence of relevant ischemic lesions according to the univariate linear regression analysis. Conclusion: Our results suggest that the higher ratio of necrotic components (based on CTA plaque analysis) could significantly increase the incidence of relevant side cerebral ischaemic lesions (classified by Fazekas-scale). Based on these findings the asymptomatic patients with high necrotic component ratio have higher risk of cerebral ischaemia thus should be operated more urgently.

Abstract Background One of the biggest health challenges in the 21st century is global climate change. The health effect of climate change is partly mediated through atmospheric parameters. There is a growing concern that atmospheric parameters might increase cardiovascular (CV) morbidity. Increased levels of haemostatic factors are predictors of CV events. The associations between CV diseases and atmospheric parameters have been widely reported, however there are few studies of atmospheric parameters' effects on markers of haemostasis. Purpose We examined the possible association between atmospheric parameters and several haemostatic markers. Methods The study consisted of 3800 hospitalized patients with acute CV diseases (ACVDs) and 260 healthy blood donors. We examined the relationship of haemoglobin (Hgb), white blood cells (WBC), thrombocytes (THR) and local atmospheric parameter conditions (temperature, atmospheric pressure, humidity, wind speed, atmospheric front) on a day-to-day basis in a 5-year period (2009–2013) using a General Additive Model with cubic splines of covariates, regularized by a ridge penalty, and employing generalized cross validation. Atmospheric parameters were allowed to have a lagged effect by up to 21 days. Results Among blood donors, the average of daily temperature lagged by 8–14 days had a significant effect on Hgb, exhibiting a U-shaped relationship, where higher Hgb values were associated with extremities of the observed temperature interval. For ACVD patients, all examined blood test variables has a significant association with at least some of the atmospheric parameters. Hgb was shown to have a negative linear relationship with mean daily humidity, and the average of daily temperature lagged by 15–21 days, while the average of daily temperature variation lagged by 2–7 days had highly non-linear effect. The relative strength of the association with Hgb was largest for daily temperature variation. WBC values had a slightly non-linear positive relationship with atmospheric pressure lagged by 1 day, with WBC being significantly increased above 1030 hPa. THR values decreased linearly with an increase in mean daily temperature averaged for days lagged 15–21. Atmospheric pressure lagged by 1 day also had a significant effect on THR, with a positive linear effect under 1010 and over 1020 hPa but no effect between. The relative effect of atmospheric pressure on THR was twice as large compared to temperature. Conclusions Our study showed that exposure to certain atmospheric parameters is associated with significant changes in haemostatic marker levels. In the context of global climate change, the importance of focusing on atmospheric parameters as minor CV risk factor is substantially growing. A better understanding of the fluctuation of the examined markers, in light of atmospheric parameters, appears to be of particular importance for future studies and could help establish new CV prevention strategies.

The local cortical activation-inhibition sequence underlying electrically evoked cortico-cortical potentials (CCEPs) is little known in humans. Our aim was to study these physiological mechanisms in drug-resistant epileptic patients implanted with subdural electrodes. To reveal the effect of cortical electrical stimulation (CES) we used intracortical laminar multielectrodes. We studied the effect of CES, applying single (10 mA, 0.5 Hz) and paired (ISI: 7–1000 ms) pulses on subdural electrodes. We analyzed the cortical depth distribution of local field potentials, current source density (CSD), changes in spectral power, and in multiple and single unit activity (MUA and SUA) in the time window of CCEPs. The laminar profile of the CCEPs showed a surface current source and middle layer sink (P1) followed by surface sink and a layer IV source (N1) associated with an increase in MUA and SUA, a surface source and a layer IV sink (P2) subsequently a cortical wide source in the middle layers (N2) accompanied by MUA and SUA decrease and a middle layer sink and increase in MUA and SUA for P3. In paired pulse setting, the amplitude differences of N1-P2 were correlated with ISI. We found similar N1-P2 curve in 8 out of 10 patients characterized by an excitation at ISI 7–10 ms, inhibition at 20–50 ms and a long interval excitation at 200–500 We identified both excitatory (P1, N1, P3) and inhibitory (P2, N2) CCEP components. In our paired pulse stimulation setting we demonstrated these inhibitory and excitatory effects on the second CCEP response.

Repetitive TMS (rTMS) represent the front-line of innovative approaches to correct dysfunctional brain networks. rTMS is FDA-approved for patients with depression, OCD and clinical trials for PTSD and substance use are underway. Despite this increasing use, knowledge of how repetitive stimulation induces brain plasticity in humans is critically lacking and will be necessary to develop next-generation personalized brain stimulation treatments. Here, we investigate the neural mechanisms underlying rTMS using direct brain recordings with high spatiotemporal resolution. We applied a single session of 10Hz prefrontal electrical stimulation, patterned to mimic rTMS, and measured intracranial EEG in 15 patients with medically-intractable epilepsy. We found that cortical regions (1) anatomically close to the stimulated site and (2) exhibiting strong evoked potentials underwent changes in excitability following stimulation. We demonstrate high accuracy (72–95%) and discriminability (81–99%) in predicting regions exhibiting changes using individual subjects’ pre-stimulation connectivity profile. We next investigated the brain dynamics during stimulation to determine how brain plasticity is induced. In each patient, we observed a four-phase response to repetitive stimulation, consisting of acute neural changes during and directly after each stimulation train as well as a buildup of effects across stimulation trains. The neural response to just one minute of stimulation reliably predicted long-term brain changes. Together this work sheds light on the mechanism underlying plasticity induction in humans. Furthermore, utilization of pre-stimulation network attributes and intra-stimulation cortical dynamics can be utilized to optimize brain stimulation technologies.

Key points Initiation of pathological synchronous events such as epileptic spikes and seizures is linked to the hyperexcitability of the neuronal network in both humans and animals. In the present study, we show that epileptiform interictal‐like spikes and seizures emerged in human neocortical slices by blocking GABAA receptors, following the disappearance of the spontaneously occurring synchronous population activity. Large variability of temporally and spatially simple and complex spikes was generated by tissue from epileptic patients, whereas only simple events appeared in samples from non‐epileptic patients. Physiological population activity was associated with a moderate level of principal cell and interneuron firing, with a slight dominance of excitatory neuronal activity, whereas epileptiform events were mainly initiated by the synchronous and intense discharge of inhibitory cells. These results help us to understand the role of excitatory and inhibitory neurons in synchrony‐generating mechanisms, in both epileptic and non‐epileptic conditions. AbstractUnderstanding the role of different neuron types in synchrony generation is crucial for developing new therapies aiming to prevent hypersynchronous events such as epileptic seizures. Paroxysmal activity was linked to hyperexcitability and to bursting behaviour of pyramidal cells in animals. Human data suggested a leading role of either principal cells or interneurons, depending on the seizure morphology. In the present study, we aimed to uncover the role of excitatory and inhibitory processes in synchrony generation by analysing the activity of clustered single neurons during physiological and epileptiform synchronies in human neocortical slices. Spontaneous population activity was detected with a 24‐channel laminar microelectrode in tissue derived from patients with or without preoperative clinical manifestations of epilepsy. This population activity disappeared by blocking GABAA receptors, and several variations of spatially and temporally simple or complex interictal‐like spikes emerged in epileptic tissue, whereas peritumoural slices generated only simple spikes. Around one‐half of the clustered neurons participated with an elevated firing rate in physiological synchronies with a slight dominance of excitatory cells. By contrast, more than 90% of the neurons contributed to interictal‐like spikes and seizures, and an intense and synchronous discharge of inhibitory neurons was associated with the start of these events. Intrinsically bursting principal cells fired later than other neurons. Our data suggest that a balanced excitation and inhibition characterized physiological synchronies, whereas disinhibition‐induced epileptiform events were initiated mainly by non‐synaptically synchronized inhibitory neurons. Our results further highlight the differences between humans and animal models, and between in vivo and (pharmacologically manipulated) in vitro conditions.

We investigated the functional network reorganization caused by low-frequency electrical stimulation (LFES) of human brain cortical surface. Intracranial EEG data from subdural grid positions were analyzed in 16 pre-surgery epileptic patients. LFES was performed by injecting current pulses (10 mA, 0.2 ms pulse width, 0.5Hz, 25 trials) into all adjacent electrode contacts. Dynamic functional connectivity analysis was carried out on two frequency bands (low: 1-4Hz; high: 10-40 Hz) to investigate the early, high frequency and late, low frequency responses elicited by the stimulation. The centralization increased in early compared to late responses, suggesting a more prominent role of direct neural links between primarily activated areas and distant brain regions. Injecting the current into the seizure onset zone (SOZ) evoked a more integrated functional topology during the early (N1) period of the response, whereas during the late (N2) period - regardless of the stimulation site - the connectedness of the SOZ was elevated compared to the non-SOZ tissue. The abnormal behavior of the epileptic sub-network during both part of the responses supports the idea of the pathogenic role of impaired inhibition and excitation mechanisms in epilepsy.

Several studies have examined the cardiovascular effects of atmospheric parameters as separate factors; however, few have investigated atmospheric parameters’ joint effects. We aim to explore the joint effects of atmospheric parameters on acute cardiovascular diseases (ACVDs) and on major cardiovascular risk factors (CRFs). We correlated all ACVD admissions with major CRFs and local atmospheric conditions during a 5-year study period. A seasonal variation was detected in a higher incidence rate during cold atmospheric conditions. There were significant incidence relative ratios, including: 1.140 (95% CI [1.020, 1.283]) for daily temperature change (≥5 °C); 0.991 (95% CI [0.988, 0.994]) for average daily temperature; and 1.290 (95% CI [1.090, 1.599]) for the interaction of daily temperature change (≥5 °C) with humidity change (≥40%). We observed a significant association between the atmospheric parameters’ joint effects and hyperlipidaemia, diabetes, and previous ACVDs. Patients with diabetes had the highest significant incidence relative ratio at 2.429 (95% CI [1.088, 5.424]) for humidity-temperature interactions. Thus, the atmospheric parameters’ joint effects play an important role as minor CRFs. These unfavourable atmospheric situations are predicted to increase the number of ACVDs mainly. Our study may help to organize prevention strategies more effectively and to reduce cardiovascular risks.