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How the human brain processes information during different cognitive tasks is one of the greatest questions in contemporary neuroscience. Understanding the statistical properties of brain signals during specific activities is one promising way to address this question. Here we analyze freely available data from implanted electrocorticography (ECoG) in five human subjects during two different cognitive tasks in the light of information theory quantifiers ideas. We employ a symbolic information approach to determine the probability distribution function associated with the time series from different cortical areas. Then we utilize these probabilities to calculate the associated Shannon entropy and a statistical complexity measure based on the disequilibrium between the actual time series and one with a uniform probability distribution function. We show that an Euclidian distance in the complexity-entropy plane and an asymmetry index for complexity are useful for comparing the two conditions. We show that our method can distinguish visual search epochs from blank screen intervals in different electrodes and patients. By using a multiscale approach and embedding time delays to downsample the data, we find important timescales in which the relevant information is being processed. We also determine cortical regions and time intervals along the 2-s-long trials that present more pronounced differences between the two cognitive tasks. Finally, we show that the method is useful to distinguish cognitive processes using brain activity on a trial-by-trial basis.

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The electrical activity of the brain, characterized by its frequency components, reflects a complex interplay between periodic (oscillatory) and aperiodic components. These components are associated with various neurophysiological processes, such as the excitation-inhibition balance (aperiodic activity) or interregional communication (oscillatory activity). However, we do not fully understand whether these components are truly independent or if different neuromodulators affect them in different ways. The dopaminergic system has a critical role for cognition and motivation, being a potential modulator of these power spectrum components. To improve our understanding of these questions, we investigated the differential effects of this system on these components using electrocorticogram recordings in cats, which show clear oscillations and aperiodic 1/f activity. Specifically, we focused on the effects of haloperidol (a D2 receptor antagonist) on oscillatory and aperiodic dynamics during wakefulness and sleep. By parameterizing the power spectrum into these two components, our findings reveal a robust modulation of oscillatory activity by the D2 receptor across the brain. Surprisingly, aperiodic activity was not significantly affected and exhibited inconsistent changes across the brain. This suggests a nuanced interplay between neuromodulation and the distinct components of brain oscillations, providing insights into the selective regulation of oscillatory dynamics in awake states.

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Alcohol, a widely commercialized psychotropic drug, and the benzodiazepine Flunitrazepam, an anxiolytic widely prescribed for patients with anxiety and insomnia problems, are well known drugs and both act on the central nervous system. The misuse and the association of these two drugs are public health concerns in several countries and could cause momentary, long-lasting and even lethal neurophysiological problems due to the potentiation of their adverse effects in synergy. The present study observed the result of the association of these drugs on electrophysiological responses in the brain, heart, and respiratory rate in Wistar rats. 8 experimental groups were determined: control, one alcohol group (20% at a dose of 1 ml/100 g VO), three Flunitrazepam groups (doses 0.1; 0.2 and 0.3 mg/kg) and three alcohol-Flunitrazepam groups (20% at a dose of 1 ml/100 g VO of alcohol, combined with 0.1; 0.2 and 0.3 mg/kg of Flunitrazepam, respectively). The results showed that there was a more pronounced reduction in alpha and theta wave power in the alcohol-Flunitrazepam groups, a decrease in the power of beta oscillations and greater sedation. There was a progressive decrease in respiratory rate linked to the increase of Flunitrazepam dose in the alcohol-Flunitrazepam associated administration. It was observed alteration in heart rate and Q-T interval in high doses of Flunitrazepam. Therefore, we conclude that the association alcohol-Flunitrazepam presented deepening of depressant synergistic effects according to the increase in the dose of the benzodiazepine, and this could cause alterations in low frequency brain oscillations, breathing, and hemodynamics of the patient.

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Characterization of brain states is essential for understanding its functioning in the absence of external stimuli. Brain states differ on their balance between excitation and inhibition, and on the diversity of their activity patterns. These can be respectively indexed by 1/f slope and Lempel-Ziv complexity (LZc). However, whether and how these two brain state properties relate remain elusive. Here we analyzed the relation between 1/f slope and LZc with two in-silico approaches and in both rat EEG and monkey ECoG data. We contrasted resting state with propofol anesthesia, which directly modulates the excitation-inhibition balance. We found convergent results among simulated and empirical data, showing a strong, inverse and non trivial monotonic relation between 1/f slope and complexity, consistent at both ECoG and EEG scales. We hypothesize that differentially entropic regimes could underlie the link between the excitation-inhibition balance and the vastness of the repertoire of brain systems.

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The Clibadium spp. is a shrub of occurrence in the Amazon, popularly known as Cunambi. The compounds in the leaves demonstrate ichthyotoxic properties, and its major substance, cunaniol, is a powerful central nervous system stimulant with proconvulsant activity. Few current studies relate behavioral changes to the electrophysiological profile of fish poisoning. This study aimed to describe the behavioral, electromyographic, electroencephalographic, electrocardiographic, and seizure control characteristics of anticonvulsant drugs in Colossoma macropomum submitted to cunaniol intoxication during bathing containing 0.3 µg/L cunaniol. The behavioral test showed rapid evolution presenting excitability and spasms, which were confirmed by the analysis of Electroencephalogram (EEG), Electromyogram (EMG), and changes in cardiac function detected in the ECG. Cunaniol-induced excitability control was evaluated using three anticonvulsant agents: Phenytoin, Phenobarbital, and Diazepam. While phenytoin was not effective in seizure control, diazepam proved to be the most efficient. These results demonstrate the susceptibility of Colossoma macropomum to cunaniol poisoning, given that the central nervous system and electrocardiographic changes were considered severe.

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Dissipative systems evolve in the preferred temporal direction indicated by the thermodynamic arrow of time. The fundamental nature of this temporal asymmetry led us to hypothesize its presence in the neural activity evoked by conscious perception of the physical world, and thus its covariance with the level of conscious awareness. We implemented a data-driven deep learning framework to decode the temporal inversion of electrocorticography signals acquired from non-human primates. Brain activity time series recorded during conscious wakefulness could be distinguished from their inverted counterparts with high accuracy, both using frequency and phase information. However, classification accuracy was reduced for data acquired during deep sleep and under ketamine-induced anesthesia; moreover, the predictions obtained from multiple independent neural networks were less consistent for sleep and anesthesia than for conscious wakefulness. Finally, the analysis of feature importance scores highlighted transitions between slow ($\approx$20 Hz) and fast frequencies (>40 Hz) as the main contributors to the temporal asymmetry observed during conscious wakefulness. Our results show that a preferred temporal direction is manifest in the neural activity evoked by conscious mentation and in the phenomenology of the passage of time, establishing common ground to tackle the relationship between brain and subjective experience.

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BACKGROUND: In the past twenty years, there has been an increasing interest among neuroscientists and physicians in mapping the cortical areas involved in the epileptogenic zone (EZ) through event-related potentials (ERPs) that enable the evaluation of the functional preservation of these areas. The present review is an update on publications on this topic. OBJECTIVE: To investigate the accuracy of the cognitive evoked of the medial temporal lobe P300 (MTL-P300) potential in detecting the EZ in temporal lobe epilepsy (TLE). METHODS: The systematic review of articles on the PubMed, Embase and Lilacs databases was conducted between February and December 2020. Articles published in English from 1985 to December 2020 were included. Additional studies were identified by searching the references of the selected studies and review articles. The studies were included for the following reasons: in-depth intracranial electroencephalography (iEEG) analysis of hippocampal activity; investigations of patients with TLE; and correlations between regarding the ERP results obtained in the temporal regions (MTL-P300) and the EZ. RESULTS: In the three studies analyzed, the authors were able to define the laterality of the EZ during the preoperative investigation through the MTL-P300 results. The sensitivity of this method was of ∼ 70% to 80%, and the specificity between 70% and 94.7%. One of the limitations of the present review was the low number of studies. CONCLUSION: There is evidence that the reduced amplitude of the MTL-P300 has high specificity in identifying the EZ, and this is a good marker for diagnosis in unilateral TLE. The low sensitivity and negative likelihood ratios negative that a normal MTL-P300 response does not exclude the epileptogenicity of the hippocampus.

ANTECEDENTES: Nos últimos 20 anos, tem havido um crescente interesse de neurocientistas e médicos em mapear áreas corticais envolvidas na zona epileptogênica (ZE) por meio de potenciais relacionados a eventos (PREs), que permitem avaliar a preservação funcional dessas áreas. Esta revisão é uma atualização das publicações sobre esse tema. OBJETIVO: Investigar a acurácia do potencial evocado cognitivo do lobo temporal medial P300 (medial temporal lobe P300, MTL-P300, em inglês) na detecção da ZE em casos de epilepsias do lobo temporal (ELT). MéTODOS: A revisão sistemática de artigos nas bases de dados PubMed, Embase e Lilacs foi realizada entre fevereiro e dezembro de 2020. Foram incluídos artigos publicados em inglês de 1985 a dezembro de 2020. Estudos adicionais foram identificados por meio de busca nas referências dos estudos selecionados e artigos de revisão. Os estudos foram incluídos pelas seguintes razões: análise detalhada por meio de eletroencefalografia intracraniana (iEEG) da atividade hipocampal; investigações de pacientes com ELT; e correlações entre os resultados de ERP obtidos nas regiões temporais (MTL-P300) e na ZE. RESULTADOS: Nos três estudos analisados, os autores foram capazes de definir a lateralidade da ZE durante a investigação pré-operatória por meio dos resultados do MTL-P300. A sensibilidade deste método foi de 70% a 80%, e a especificidade, entre 70% e 94.7%. Uma das limitações desta revisão foi o baixo número de estudos. CONCLUSãO: Há evidências de que a amplitude reduzida do MTL-P300 tem alta especificidade na identificação da ZE, e este é um bom marcador para o diagnóstico na ELT unilateral. A baixa sensibilidade e a razão de verossimilhança negativa indicam que a resposta MTL-P300 normal não exclui a epileptogenicidade do hipocampo.

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Camphor is an aromatic terpene compound found in the essential oils of many plants, which has been used for centuries as a herbal medicine, especially in children. However, many studies have shown that camphor may have major side effects, including neurological manifestation, such as seizures. In the present study, we investigated the electrocorticographic patterns of seizures induced by camphor in male adult Wistar rats. Each rat received 400 mg/kg (i.p.) of camphor prior to monitoring by electrocorticography. The application of camphor resulted a rapid evolution to seizure and marked changes in the electrocorticographic readings, which presented characteristics of epileptiform activity, with an increase in the total power wave. The decomposition of the cerebral waves revealed an increase in the delta and theta waves. The analysis of the camphor traces revealed severe ictal activity marked by an increase in the polyspike wave. Our data thus indicate that camphor may cause seizures, leading to tonic-clonic seizures. Clearly, further studies are necessary to better elucidate the mechanisms through which camphor acts on the brain, and to propose potential treatments with anticonvulsant drugs that are effective for the control of the seizures.

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We report a patient with reflex tooth-brushing-triggered epilepsy, associated with a post-central lesion within the right somatosensory face area. Contralateral facial sensory and motor phenomena, associated with contralateral upper limb extension, were present at seizure onset after gingival stimulation, but seizures could also be induced by contact with solid food or liquids. Spontaneous seizures also were recorded. Secondary generalization was infrequent. Stereoelectroencephalography implantation was performed, with seizure recording and cortical/subcortical stimulation for mapping, to identify the precise extent of surgical resection. Complete postoperative control of epilepsy was achieved, accompanied by a mild and transient neurological deficit. [Published with video sequence].

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In construing meaning, the brain recruits multimodal (conceptual) systems and embodied (modality-specific) mechanisms. Yet, no consensus exists on how crucial the latter are for the inception of semantic distinctions. To address this issue, we combined electroencephalographic (EEG) and intracranial EEG (iEEG) to examine when nouns denoting facial body parts (FBPs) and nonFBPs are discriminated in face-processing and multimodal networks. First, FBP words increased N170 amplitude (a hallmark of early facial processing). Second, they triggered fast (~100 ms) activity boosts within the face-processing network, alongside later (~275 ms) effects in multimodal circuits. Third, iEEG recordings from face-processing hubs allowed decoding ~80% of items before 200 ms, while classification based on multimodal-network activity only surpassed ~70% after 250 ms. Finally, EEG and iEEG connectivity between both networks proved greater in early (0-200 ms) than later (200-400 ms) windows. Collectively, our findings indicate that, at least for some lexico-semantic categories, meaning is construed through fast reenactments of modality-specific experience.

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Adaptive behavior requires the comparison of outcome predictions with actual outcomes (e.g., performance feedback). This process of performance monitoring is computed by a distributed brain network comprising the medial prefrontal cortex (mPFC) and the anterior insular cortex (AIC). Despite being consistently co-activated during different tasks, the precise neuronal computations of each region and their interactions remain elusive. In order to assess the neural mechanism by which the AIC processes performance feedback, we recorded AIC electrophysiological activity in humans. We found that the AIC beta oscillations amplitude is modulated by the probability of performance feedback valence (positive or negative) given the context (task and condition difficulty). Furthermore, the valence of feedback was encoded by delta waves phase-modulating the power of beta oscillations. Finally, connectivity and causal analysis showed that beta oscillations relay feedback information signals to the mPFC. These results reveal that structured oscillatory activity in the anterior insula encodes performance feedback information, thus coordinating brain circuits related to reward-based learning.

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BACKGROUND: Understanding the configuration of neural circuits and the specific role of distinct cortical neuron types involved in behavior, requires the study of structure-function and connectivity relationships with single cell resolution in awake behaving animals. Despite head-fixed behaving rats have been used for in vivo measuring of neuronal activity, it is a concern that head fixation could change the performance of behavioral task. NEW METHOD: We describe the procedures for efficiently training Wistar rats to develop a behavioral task, involving planning and execution of a qualified movement in response to a visual cue under head-fixed conditions. The behavioral and movement performance in freely moving vs head-fixed conditions was analyzed. RESULTS: The best behavioral performance was obtained in the rats that were trained first in freely moving conditions and then placed in a head-restrained condition compared with the animals which first were habituated to head-restriction and then learned the task. Moreover, head restriction did not alter the movement performance. Stable juxtacellular recordings from sensorimotor cortex neurons were obtained while the rats were performing forelimb movements. Biocytin electroporation and retrograde tracer injections, permits identify the hodology of individual long-range projecting neurons. COMPARISON WITH EXISTING METHODS: Our method shows no difference in the behavioral performance of head fixed and freely moving conditions. Also includes a computer aided design of a discrete and ergonomic head-post allowing enough stability to perform juxtacellular recording and labeling of cortical neurons. CONCLUSIONS: Our method is suitable for the in vivo characterization of neuronal circuits and their long-range connectivity.

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In most mammals, the sleep-wake cycle is constituted by three behavioral states: wakefulness (W), non-REM (NREM) sleep, and REM sleep. These states are associated with drastic changes in cognitive capacities, mostly determined by the function of the thalamo-cortical system. The intra-cranial electroencephalogram or electocorticogram (ECoG), is an important tool for measuring the changes in the thalamo-cortical activity during W and sleep. In the present study we analyzed broad-band ECoG recordings of the rat by means of a time-series complexity measure that is easy to implement and robust to noise: the Permutation Entropy (PeEn). We found that PeEn is maximal during W and decreases during sleep. These results bring to light the different thalamo-cortical dynamics emerging during sleep-wake states, which are associated with the well-known spectral changes that occur when passing from W to sleep. Moreover, the PeEn analysis allows us to determine behavioral states independently of the electrodes' cortical location, which points to an underlying global pattern in the signal that differs among the cycle states that is missed by classical methods. Consequently, our data suggest that PeEn analysis of a single EEG channel could allow for cheap, easy, and efficient sleep monitoring.

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OBJECTIVE: Drug-resistant focal epilepsy is widely recognized as a network disease in which epileptic seizure propagation is likely coordinated by different neuronal oscillations such as low-frequency activity (LFA), high-frequency activity (HFA), or low-to-high cross-frequency coupling. However, the mechanism by which different oscillatory networks constrain the propagation of focal seizures remains unclear. METHODS: We studied focal epilepsy patients with invasive electrocorticography (ECoG) recordings and compared multilayer directional network interactions between focal seizures either with or without secondary generalization. Within-frequency and cross-frequency directional connectivity were estimated by an adaptive directed transfer function and cross-frequency directionality, respectively. RESULTS: In the within-frequency epileptic network, we found that the seizure onset zone (SOZ) always sent stronger information flow to the surrounding regions, and secondary generalization was accompanied by weaker information flow in the LFA from the surrounding regions to SOZ. In the cross-frequency epileptic network, secondary generalization was associated with either decreased information flow from surrounding regions' HFA to SOZ's LFA or increased information flow from SOZ's LFA to surrounding regions' HFA. INTERPRETATION: Our results suggest that the secondary generalization of focal seizures is regulated by numerous within- and cross-frequency push-pull dynamics, potentially reflecting impaired excitation-inhibition interactions of the epileptic network. ANN NEUROL 2019;86:683-694.

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Vortioxetine is a multimodal antidepressant agent that modulates 5-HT receptors and inhibits the serotonin transporter. It is indicated especially in cases of major depressive disorder related to cognitive dysfunction. There are many studies investigating the effects of antidepressants on the seizure threshold and short-term epileptic activity. However, the effect of vortioxetine on epileptic seizures is not exactly known. Our aim was to investigate the effects of vortioxetine on penicillin-induced epileptiform activity. Twenty-seven Wistar rats were divided into three groups: sham-control group, positive control group (diazepam), and vortioxetine group. After a penicillin-induced epilepsy model was formed in each of the three groups of animals, 0.1 ml of saline was administered to the control group, 0.1 ml (10 mg/kg) vortioxetine was administered in the vortioxetine group, and 0.1 mL (5 mg/kg) of diazepam was administered in the positive control group, intraperitoneally. The epileptic activity records were obtained for 120 minutes after the onset of seizure. There was no significant difference in spike wave activity between the vortioxetine and diazepam groups, whereas this was significantly reduced in the vortioxetine group compared with the controls. The administration of vortioxetine at a dose of 10 mg/kg immediately after the seizure induction significantly decreased the spike frequencies of epileptiform activity compared with the control group. No significant difference was found between the vortioxetine and positive controls. This study showed that vortioxetine reduces the number of acutely-induced epileptic discharges. Vortioxetine may be an important alternative for epileptic patients with major depressive disorder-related cognitive dysfunction.

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INTRODUCTION: Epilepsy in pediatric age are frequently associated with cognitive disorders. Different studies correlated the presence of transient cognitive disorders with the presence of interictal epileptiform discharges (IEDs). CASE REPORT: A 23-year-old woman with pharmacoresistant focal epilepsy was evaluated with invasive videoEEG in the context of epilepsy surgery. There were selected 300 periods of 10 seconds duration from the invasive videoEEG, which were classified into two groups. Group 1 showed IEDs restricted to the cortex of the middle frontal gyrus, inferior temporal gyrus, left lateral and medial occipitotemporal gyrus (dominant hemisphere). In group 2, IEDs was observed in the upper and middle frontal gyrus, precentral, the inferior and middle temporal left gyrus. The patient read the same text during the selected peirods. The number of words read in each period was counted. The working memory was evaluated by the inverse digit test. In group 1, the average number of words read was 10.2 (95% CI: 10.04-10.35); in group 2 it was 2.3 (95% CI: 2.12-2.27; t(146) = 94.55; p < 0.0001). In group 1, the average of inverse digits was 4.05 (95% CI: 3.81-4.30); in group 2 it was 2.67 (95% CI: 2.48-2.86; t(33) = 10.34; p < 0.0001). CONCLUSIONS: Our finding allows us to infer that the interference of IEDs in the cortex of the upper and middle frontal gyrus, precentral, middle and lower temporal gyrus of the dominant hemisphere, causes a dysfunction of neural networks involved in reading.

TITLE: Trastornos transitorios de la lectura asociados a descargas paroxisticas epileptiformes interictales en videocorticografia invasiva.Introduccion. La epilepsia en la edad pediatrica se asocia frecuentemente a trastornos cognitivos. Distintos estudios correlacionaron la presencia de trastornos cognitivos transitorios con la presencia de descargas epilepticas interictales (DEI). Caso clinico. Mujer de 23 años, con epilepsia focal farmacorresistente evaluada con videoelectroencefalograma (video-EEG) invasivo en el contexto de cirugia de la epilepsia. Del video-EEG invasivo se seleccionaron 300 epocas de 10 s de duracion, que se clasificaron en dos grupos. El grupo 1 evidencio DEI restringidas a la corteza del giro frontal medio, el giro temporal inferior y los giros occipitotemporales lateral y medial izquierdos (hemisferio dominante). En el grupo 2 se observaron DEI en el giro frontal superior y medio, el giro precentral y los giros temporales medio e inferior izquierdos. La paciente leyo el mismo texto durante las epocas seleccionadas. Se contabilizo el numero de palabras leidas en cada epoca. Se evaluo la memoria de trabajo mediante la prueba de digitos inversos. En el grupo 1, la media de palabras leidas fue de 10,2 (IC 95%: 10,04-10,35); en el grupo 2, de 2,3 (IC 95%: 2,12-2,27; t(146) = 94,55; p < 0,0001). En el grupo 1, la media de digitos inversos fue de 4,05 (IC 95%: 3,81-4,30); en el grupo 2, de 2,67 (IC 95%: 2,48-2,86; t(33) = 10,34; p < 0,0001). Conclusion. El hallazgo permite inferir que la interferencia de las DEI en la corteza del giro frontal superior y medio, el giro precentral, y los giros temporales medio e inferior del hemisferio dominante provoca una disfuncion de las redes neuronales implicadas en los mecanismos de la lectura.

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ABSTRACT Vortioxetine is a multimodal antidepressant agent that modulates 5-HT receptors and inhibits the serotonin transporter. It is indicated especially in cases of major depressive disorder related to cognitive dysfunction. There are many studies investigating the effects of antidepressants on the seizure threshold and short-term epileptic activity. However, the effect of vortioxetine on epileptic seizures is not exactly known. Our aim was to investigate the effects of vortioxetine on penicillin-induced epileptiform activity. Twenty-seven Wistar rats were divided into three groups: sham-control group, positive control group (diazepam), and vortioxetine group. After a penicillin-induced epilepsy model was formed in each of the three groups of animals, 0.1 ml of saline was administered to the control group, 0.1 ml (10 mg/kg) vortioxetine was administered in the vortioxetine group, and 0.1 mL (5 mg/kg) of diazepam was administered in the positive control group, intraperitoneally. The epileptic activity records were obtained for 120 minutes after the onset of seizure. There was no significant difference in spike wave activity between the vortioxetine and diazepam groups, whereas this was significantly reduced in the vortioxetine group compared with the controls. The administration of vortioxetine at a dose of 10 mg/kg immediately after the seizure induction significantly decreased the spike frequencies of epileptiform activity compared with the control group. No significant difference was found between the vortioxetine and positive controls. This study showed that vortioxetine reduces the number of acutely-induced epileptic discharges. Vortioxetine may be an important alternative for epileptic patients with major depressive disorder-related cognitive dysfunction.

RESUMO A vortioxetina é um agente antidepressivo multimodal que modula os receptores 5HT e inibe o transportador de serotonina. Está indicada, principalmente nos casos de transtorno depressivo maior (TDM), relacionado à disfunção cognitiva. Existem muitos estudos que investigam os efeitos dos antidepressivos no limiar convulsivo e na atividade epiléptica de curto prazo. No entanto, o efeito da vortioxetina nas crises epilépticas não é exatamente conhecido. Nosso objetivo é investigar os efeitos da vortioxetina sobre a atividade epileptiforme induzida pela penicilina. Vinte e sete ratos Wistar foram divididos em três grupos, grupo controle-sham, grupo controle positivo (Diazepam) e grupo vortioxetina. Depois, 0,1 mg (10 mg / kg) de vortioxetina foi administrado no grupo vortioxetina, e 0,1 ml (5 mg / kg) / kg) de diazepam foi administrado no grupo de controle positivo intraperitonealmente. Os registros de atividade epiléptica foram obtidos durante 120 minutos após o início da convulsão. Não houve diferença significativa na atividade de pico entre o grupo de voritoxetina e diazepam, embora tenha sido significativamente reduzida no grupo de vortioxetina em comparação com os controles. A administração de vortioxetina na dose de 10 mg / kg imediatamente após a indução das convulsões diminuiu significativamente as frequências de espícula da atividade epileptiforme em comparação com o grupo controle. Nenhuma diferença significativa foi encontrada entre a vortioxetina e controles positivos. Este estudo mostrou que a vortioxetina reduz o número de descargas epilépticas agudamente induzidas. A vortioxetina pode ser uma alternativa importante para pacientes epilépticos com disfunção cognitiva relacionada à TDM.

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Abstract Background Acute myeloid leukemia (AML) is a potentially fatal hematological disease. Along with disease-related factors, patient-related factors, in particular age, are a strong predictor of outcome that influence treatment decisions. Many acute myeloid leukemia risk stratification models have been developed to predict the outcome of intensive chemotherapy. However, these models did not include physical function assessments. Methods This study investigated the impact of several factors, namely the performance status, physical function and age on the short-term outcomes of intensive chemotherapy in a cohort of 50 Egyptian patients with de novo acute myeloid leukemia. Results Complete remission after intensive chemotherapy in these myeloid leukemia patients at Day 28 was 56% and the mortality rate was 12% and 34% at Day 28 and Day 60, respectively. The pretreatment Eastern Cooperative Oncology Group score was significantly correlated with outcomes on Day 28 and Day 60 (p-value = 0.041 and p-value = 0.032, respectively). There were significant correlations between the two-minute walk test and outcomes of therapy on Day 28 and 60 (p-value = 0.032 and p-value = 0.047, respectively) and between grip strength test and outcomes of therapy on Day 28 and 60 (p-value = 0.046 and p-value = 0.047 respectively). Furthermore, there was a significant correlation between chair stand test and outcome of therapy on Day 28 (p-value = 0.023). Conclusion Performance status and physical function assessments were strong predictors of outcome of intensive chemotherapy in acute myeloid leukemia and we recommend the incorporation of these variables in risk stratification models for the personalization of therapy before treating acute myeloid leukemia patients with intensive chemotherapy.

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OBJECTIVE: Analyze the hypothesis that swimming exercise, in rats suckled under distinct litter sizes, alters behavioral parameters suggestive of anxiety and recognition memory, and the electrocorticogram potentiation that occurs after the excitability-related phenomenon that is known as cortical spreading depression (CSD). METHODS: Male Wistar rats were suckled in litters with six or 12 pups (L6 and L12 groups). Animals swam at postnatal days (P) 8-23, or P60-P75 (early-exercised or late-exercised groups, respectively), or remained no-exercised. Behavioral tests (open field - OF and object recognition - OR) were conducted between P77 and P80. Between P90 and P120, ECoG was recorded for 2 hours. After this 'baseline' recording, CSD was elicited every 30 minutes over the course of 2 hours. RESULTS: Early swimming enhanced the number of entries and the percentage of time in the OF-center (P < 0.05). In animals that swam later, this effect occurred in the L6 group only. Compared to the corresponding sedentary groups, OR-test showed a better memory in the L6 early exercised rats, and a worse memory in all other groups (P < 0.05). In comparison to baseline values, ECoG amplitudes after CSD increased 14-43% for all groups (P < 0.05). In the L6 condition, early swimming and late swimming, respectively, reduced and enhanced the magnitude of the post-CSD ECoG potentiation in comparison with the corresponding L6 no-exercised groups (P < 0.05). DISCUSSION: Our data suggest a differential effect of early- and late-exercise on the behavioral and electrophysiological parameters, suggesting an interaction between the age of exercise and the nutritional status during lactation.

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