Cytochrome 1A1 and 1B1 gene diversity in the Zanzibar islands.

Amodiaquine (AQ) is a 4-aminoquinoline widely used in the treatment of malaria as part of the artemisinin combination therapy (ACT). AQ is metabolised towards its main metabolite desethylamodiaquine mainly by cytochrome P450 2C8 (CYP2C8). CYP1A1 and CYP1B1 play a minor role in the metabolism but they seem to be significantly involved in the formation of the short-lived quinine-imine. To complete the genetic variation picture of the main genes involved in AQ metabolism in the Zanzibar population, previously characterised for CYP2C8, we analysed in this study CYP1A1 and CYP1B1 main genetic polymorphisms. The results obtained show a low frequency of the CYP1A1*2B/C allele (2.4%) and a high frequency of CYP1B1*6 (approximately 42%) followed by CYP1B1*2 (approximately 27%) in Zanzibar islands. Genotype data for CYP1A1 and CYP1B1 show a low incidence of fast metabolisers, revealing a relatively safe genetic background in Zanzibar's population regarding the appearance of adverse effects.

Differential effects of clinically used derivatives and metabolites of artemisinin in the activation of constitutive androstane receptor isoforms.

BACKGROUND AND PURPOSE: Widespread resistance to antimalarial drugs requires combination therapies with increasing risk of pharmacokinetic drug-drug interactions. Here, we explore the capacity of antimalarial drugs to induce drug metabolism via activation of constitutive androstane receptors (CAR) by ligand binding. EXPERIMENTAL APPROACH: A total of 21 selected antimalarials and 11 major metabolites were screened for binding to CAR isoforms using cellular and in vitro CAR-coactivator interaction assays, combined with in silico molecular docking. Identified ligands were further characterized by cell-based assays and primary human hepatocytes were used to elucidate induction of gene expression. KEY RESULTS: Only two artemisinin derivatives arteether and artemether, the metabolite deoxyartemisinin and artemisinin itself demonstrated agonist binding to the major isoforms CAR1 and CAR3, while arteether and artemether were also inverse agonists of CAR2. Dihydroartemisinin and artesunate acted as weak inverse agonists of CAR1. While arteether showed the highest activities in vitro, it was less active than artemisinin in inducing hepatic CYP3A4 gene expression in hepatocytes. CONCLUSIONS AND IMPLICATIONS: Artemisinin derivatives and metabolites differentially affect the activities of CAR isoforms and of the pregnane X receptor (PXR). This negates a common effect of these drugs on CAR/PXR-dependent induction of drug metabolism and further provides an explanation for artemisinin consistently inducing cytochrome P450 genes in vivo, whereas arteether and artemether do not. All these drugs are metabolized very rapidly, but only artemisinin is converted to an enzyme-inducing metabolite. For better understanding of pharmacokinetic drug-drug interaction possibilities, the inducing properties of artemisinin metabolites should be considered.

Gamma band oscillations in parietooccipital areas during performance of a sensorimotor integration task: a qEEG coherence study / Oscilações na banda gama em áreas parieto-occipitais durante desempenho de uma tarefa sensório-motora: um estudo de coerência na EEGq

This study aimed to elucidate cortical mechanisms involved in anticipatory actions when 23 healthy right-handed subjects had to catch a free falling object through quantitative electroencephalogram (qEEG). For this reason, we used coherence that represents a measurement of linear covariation between two signals in the frequency domain. In addition, we investigated gamma-band (30-100 Hz) activity that is related to cognitive and somatosensory processes. We hypothesized that gamma coherence will be increase in both parietal and occipital areas during moment after ball drop, due to their involvement in manipulation of objects, visuospatial processing, visual perception, stimuli identification and attention processes. We confirmed our hypothesis, an increase in gamma coherence on P3-P4 (t= -2.15; p=0.033) and PZ-OZ (t= -2.16; p=0.034) electrode pairs was verified for a paired t-test. We conclude that to execute tasks involving anticipatory movements (feedforward mechanisms), like our own task, probably, there is no need of a strong participation of visual areas in the process of information organization to manipulate objects and to process visuospatial information regarding the contact hand-object.

Este estudo teve como objetivo elucidar os mecanismos corticais envolvidos em ações antecipatórias quando 23 indivíduos saudáveis destros tinham que apreender um objeto em queda livre, através da eletroencefalografia quantitativa (EEGq). Por esta razão, usamos a coerência que representa a covariação linear entre dois sinais no domínio da frequência. Além disso, investigamos a atividade da banda gama (30-100 Hz), que está relacionada à processos cognitivos e somato-sensoriais. Nossa hipótese é que a coerência de gama estará aumentada em ambas as áreas parietais e occipitais durante o momento pós-queda da bola, devido ao seu envolvimento na manipulação de objetos, processamento visuo-espacial, percepção visual, identificação de estímulos e processos de atenção. Confirmamos nossa hipótese. Um aumento de coerência em gama nos pares de eletrodos P3-P4 (t= -2,15; p=0,033) e PZ-OZ (t= -2,16; p=0,034) foi verificado por teste-t pareado. Conclui-se que, para executar tarefas que envolvem movimentos de antecipação (mecanismos de retro-alimentação) como a nossa própria tarefa, provavelmente, não há necessidade de forte participação de áreas visuais no processo de organização da informação como para manipular objetos e processar a informação visuo-espacial no contato mão-objeto.

Corticomuscular coherence behavior in fine motor control of force: a critical review.

INTRODUCTION: Understanding how the human motor control operates is an important issue to the neuroscience. One example is how the motor cortex controls muscle activity, which can be observed through corticomuscular coherence (CMC). AIM: Our study aimed to verify the influence of certain factors related to the fine motor control of force tasks on CMC. Our issue is if would be possible the strength of the coupling between the central and muscular systems measured by changes in oscillatory activity of beta- and gamma-band being influenced by these factors as much healthy subjects as patients. DEVELOPMENT: Beta-band CMC was especially important when executing sustaining accurate control tasks, which need more concentration and effort. However, we found that beta-band CMC was influenced by some factors. With regard to gamma-band CMC, apparently a complex and continuous dynamic integration of several mechanisms would be necessary to modulate gamma-band CMC, since it was not modulated by magnitude of force. Therefore, it seems these mechanisms would be required to an adequate and effective neural networks operation when a dynamic force output is required. CONCLUSION: Beta- and gamma-band CMC could enrich our understanding of the dynamic changes of the motor system not only in health subjects but also in neurological patients. It may serve as a sensitive index for quantifying dynamical changes in fine motor control of force. It has the potential to become a useful tool to characterize the patterns of changes in central nervous system's activities for the purposes of basic research, especially in restoring of motor function.

Effect of aerobic training on EEG alpha asymmetry and depressive symptoms in the elderly: a 1-year follow-up study

The effect of physical exercise on the treatment of depressive elderly adults has not been investigated thus far in terms of changes in cortical hemispheric activity. The objective of the present study was to identify changes in depressive symptoms, quality of life, and cortical asymmetry produced by aerobic activity. Elderly subjects with a diagnosis of major depressive disorder (DSM-IV) were included. Twenty patients (70 percent females, 71 ± 3 years) were divided into an exercise group (pharmacological treatment plus aerobic training) and a control group (undergoing pharmacological treatment) in a quasi-experimental design. Pharmacological treatment was maintained stable throughout the study (antidepressants and anxiolytics). Subjects were evaluated by depression scales (Beck Depression Inventory, Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale) and the Short Form Health Survey-36, and electroencephalographic measurements (frontal and parietal alpha asymmetry) before and after 1 year of treatment. After 1 year, the control group showed a decrease in cortical activity on the right hemisphere (increase of alpha power), which was not observed in the exercise group. The exercise group showed a significant decrease of depressive symptoms, which was not observed in the control group. This result was also accompanied by improved treatment response and remission rate after 1 year of aerobic exercise associated with treatment. This study provides support for the effect of aerobic training on alpha activity and on depressive symptoms in elderly patients. Exercise facilitates the treatment of depressive elderly adults, leading to clinical and physical improvement and protecting against a decrease in cortical activity.

Effect of aerobic training on EEG alpha asymmetry and depressive symptoms in the elderly: a 1-year follow-up study.

The effect of physical exercise on the treatment of depressive elderly adults has not been investigated thus far in terms of changes in cortical hemispheric activity. The objective of the present study was to identify changes in depressive symptoms, quality of life, and cortical asymmetry produced by aerobic activity. Elderly subjects with a diagnosis of major depressive disorder (DSM-IV) were included. Twenty patients (70% females, 71 +/- 3 years) were divided into an exercise group (pharmacological treatment plus aerobic training) and a control group (undergoing pharmacological treatment) in a quasi-experimental design. Pharmacological treatment was maintained stable throughout the study (antidepressants and anxiolytics). Subjects were evaluated by depression scales (Beck Depression Inventory, Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale) and the Short Form Health Survey-36, and electroencephalographic measurements (frontal and parietal alpha asymmetry) before and after 1 year of treatment. After 1 year, the control group showed a decrease in cortical activity on the right hemisphere (increase of alpha power), which was not observed in the exercise group. The exercise group showed a significant decrease of depressive symptoms, which was not observed in the control group. This result was also accompanied by improved treatment response and remission rate after 1 year of aerobic exercise associated with treatment. This study provides support for the effect of aerobic training on alpha activity and on depressive symptoms in elderly patients. Exercise facilitates the treatment of depressive elderly adults, leading to clinical and physical improvement and protecting against a decrease in cortical activity.

[The effects of bromazepam on the performance of a sensory-motor activity: an electroencephalographic study]. / Efectos del bromacepam en el desarrollo de una actividad sensoriomotora: un estudio electroencefalográfico.

AIMS: To investigate the effects of using bromazepam on the relative power in alpha while performing a typing task. Bearing in mind the particularities of each brain hemisphere, our hypothesis was that measuring the relative power would allow us to investigate the effects of bromazepam on specific areas of the cortex. More specifically, we expected to observe different patterns of powers in sensory-motor integration, attention and activation processes. SUBJECTS AND METHODS: The sample was made up of 39 subjects (15 males and 24 females) with a mean age of 30 +/- 10 years. The control (placebo) and experimental (3 mg and 6 mg of bromazepam) groups were trained in the typing task with a randomised double-blind model. RESULTS: A three-way ANOVA and Scheffé test were used to analyse interactions between the factors condition and moment, and between condition and sector. CONCLUSIONS: The doses used in this study facilitated motor performance of the typing task. In this study, the use of the drug did not prevent learning of the task, but it did appear to concentrate mental effort on more restricted and specific aspects of typing. It also seemed to influence the rhythm and effectiveness of the operations performed during mechanisms related to the encoding and storage of new information. Likewise, a predominance of activity was observed in the left (dominant) frontal area in the 3 mg bromazepam group, which indicates that this dose of the drug affords the subject a greater degree of directionality of cortical activity for planning and performing the task.

Efectos del bromacepam en el desarrollo de una actividad sensoriomotora: un estudio electroencefalográfico / The effects of bromazepan on the performance of a sensory-motor activity: an electroencephalographic study

Objetivos. Investigar los efectos del uso del bromacepam en la potencia relativa en alfa durante la realización de unatarea de mecanografía. Teniendo en cuenta las particularidades de cada hemisferio cerebral, nuestra hipótesis era que a travésde la medida de la potencia relativa sería posible investigar el efecto del bromacepam sobre áreas corticales específicas. Concretamente,se esperaba observar diferentes patrones de potencias en los procesos de atención, activación e integración sensoriomotora.Sujetos y métodos. La muestra estaba formada por 39 sujetos (15 hombres y 24 mujeres) con una media de edad de30 ± 10 años. Los grupos control (placebo) y experimental (bromacepam de 3 mg y 6 mg) fueron entrenados en la tarea de mecanografíacon un modelo doble ciego aleatorizado. Resultados. Mediante el ANOVA de tres vías y el test de Scheffé se comprobaroninteracciones entre los factores condición y momento y entre condición y sector. Conclusión. Las dosis empleadas en esteestudio facilitaron el desarrollo motor de la tarea de mecanografía. En este estudio, el uso del fármaco no impidió el aprendizajede la tarea, pero parece ser que concentró el esfuerzo mental sobre aspectos más restringidos y específicos de la mecanografía.Tuvo lugar una influencia sobre el ritmo y la eficacia de las operaciones ejecutadas durante mecanismos de codificacióny almacenamiento de nuevas informaciones. Asimismo, se comprobó un predominio de actividad en el área frontal izquierda(dominante) en el grupo bromacepam 3 mg, lo cual indica que esta dosis del fármaco permite al sujeto un mayor direccionamientode la actividad cortical para la planificación y la ejecución de la tarea(AU)

Aims. To investigate the effects of using bromazepam on the relative power in alpha while performing a typing task.Bearing in mind the particularities of each brain hemisphere, our hypothesis was that measuring the relative power wouldallow us to investigate the effects of bromazepam on specific areas of the cortex. More specifically, we expected to observedifferent patterns of powers in sensory-motor integration, attention and activation processes. Subjects and methods. The samplewas made up of 39 subjects (15 males and 24 females) with a mean age of 30 ± 10 years. The control (placebo) and experimental(3 mg and 6 mg of bromazepam) groups were trained in the typing task with a randomised double-blind model. Results. A threewayANOVA and Scheffé test were used to analyse interactions between the factors condition and moment, and betweencondition and sector. Conclusions. The doses used in this study facilitated motor performance of the typing task. In this study,the use of the drug did not prevent learning of the task, but it did appear to concentrate mental effort on more restricted andspecific aspects of typing. It also seemed to influence the rhythm and effectiveness of the operations performed duringmechanisms related to the encoding and storage of new information. Likewise, a predominance of activity was observed in theleft (dominant) frontal area in the 3 mg bromazepam group, which indicates that this dose of the drug affords the subject agreater degree of directionality of cortical activity for planning and performing the task(AU)

[The role played by the parietooccipital cortex in the process of sensory-motor integration: an electroencephalographic study]. / Participación de la corteza parietooccipital en el proceso de integración sensoriomotora: estudio electroencefalográfico.

INTRODUCTION: A fundamental aspect of planning future actions is the performance and control of motor tasks. This behaviour is done through sensory-motor integration. AIM: To explain the electrophysiological mechanisms in the cortex (modifications to the alpha band) that are involved in anticipatory actions when individuals have to catch a free-falling object. SUBJECTS AND METHODS: The sample was made up of 20 healthy subjects of both sexes (11 males and 9 females) with ages ranging between 25 and 40 years (32.5 +/- 7.5) who were free of mental or physical diseases (previous medical history); the subjects were right-handed (Edinburgh Inventory) and were not taking any psychoactive or psychotropic substances at the time of the study. The experiment consisted in a task in which subjects had to catch freely falling objects. The experiment was made up of six blocks of 15 tests, each of which lasted 2 minutes and 30 seconds, with a break of one minute between blocks. Data were captured by means of a quantitative electroencephalogram two seconds before and two seconds after each ball was dropped. RESULTS: An interaction of the factors moment and position was only observed for the right parietooccipital cortex, in the combination of electrodes P4-O2. CONCLUSION: These findings suggest that the right parietooccipital cortex plays an important role in increasing expectation and swiftness in the processes of preparing for a motor task.

Relationship between CYP2C8 genotypes and diclofenac 5-hydroxylation in healthy Spanish volunteers.

PURPOSE: CYP2C8 seems to be involved in diclofenac 5-hydroxylation, while, in vitro, the 4'-hydroxylation and 3'-hydroxylation seem to be mediated mainly by CYP2C9. We have demonstrated the relevance of CYP2C9 genotypes for diclofenac 4'-hydroxylation in healthy volunteers, so that the present study was aimed at analyzing the role of both CYP2C8 and CYP2C9 genotypes on diclofenac metabolism, as well as determining the CYP2C8 allele frequencies and their relationship with CYP2C9 variants. METHODS: A group of 142 healthy white Spanish volunteers was studied. Previously, 102 of these subjects had been phenotyped with diclofenac and genotyped for CYP2C9. The CYP2C8 genotypes were determined by allele-specific PCR-RFLP methods. The urinary concentrations of diclofenac and its main metabolites were analysed using an HPLC-UV method after the administration of a single oral dose of diclofenac as described previously for part of the population studied here. RESULTS: The diclofenac/5-hydroxydiclofenac urinary concentration ratio was higher in individuals carrying a CYP2C8*3 or CYP2C8*4 allele than in those homozygous for wild-type allele CYP2C8*1 (P < 0.05). Moreover, approximately 93% of the subjects with a CYP2C8*3 allele also carried a CYP2C9*2, and 80% of the subjects that had CYP2C9*2 variant also carried a CYP2C8*3. In addition, the four CYP2C9*2/*2 individuals were CYP2C8*3/*3. CONCLUSIONS: This is the first study showing the influence of CYP2C8 genotypes on diclofenac metabolism in vivo. The linkage disequilibrium between CYP2C8*3 and CYP2C9*2 alleles was confirmed in this Spanish population.

[Learning and implicit memory: mechanisms and neuroplasticity]. / Aprendizaje y memoria implícita: mecanismos y neuroplasticidad.

INTRODUCTION: Learning and memory are complex processes that researchers have been attempting to unravel for over a century in order to gain a clear view of the underlying mechanisms. AIMS: To review the basic cellular and molecular mechanisms involved in the process of procedural retention, to offer an overall view of the fundamental mechanisms involved in storing information by means of theories and models of memory, and to discuss the different types of memory and the role played by the cerebellum as a modulator of procedural memory. DEVELOPMENT: Experimental results from recent decades have opened up new areas of study regarding the participation of the biochemical and cellular processes related to the consolidation of information in the nervous system. CONCLUSIONS: The neuronal circuits involved in acquiring and consolidating memory are still not fully understood and the exact location of memory in the nervous system remains unknown. A number of intrinsic and extrinsic factors interfere in these processes, such as molecular (long-term potentiation and depression) and cellular mechanisms, which respond to communication and transmission between nerve cells. There are also factors that have their origin in the outside environment, which use the association of events to bring about the formation of new memories or may divert the subject from his or her main focus. Memory is not a singular occurrence; it is sub-divided into declarative and non-declarative or, when talking about the time it lasts, into short and long-term memory. Moreover, given its relation with neuronal mechanisms of learning, memory cannot be said to constitute an isolated process.

[The effects of bromazepam on contingent negative variation and reaction time in a visuomotor task]. / Efectos del bromacepam sobre la variación negativa contingente y el tiempo de reacción en una tarea visuomotora.

INTRODUCTION: Bromazepam is the second most commonly used benzodiazepine in Brazil. Psychophysiological research on this substance is still in its early stages. AIM: To determine the neurotoxicity of bromazepam by examining reaction times (RT) and contingent negative variations (CNV). SUBJECTS AND METHODS: Using a videogame produced in our laboratory for psychophysiological research purposes (Car Acquisition), 14 healthy volunteers (9 males) aged between 23 and 42 drove a vehicle along a road full of curves (i.e. distractors) while they had to respond to imperative stimuli (i.e. orders to press the button on the joystick) that were preceded by warnings (S1-S2-RM paradigm with distractor). We compared RT, amplitudes and latencies of the CNV at each of the three electrodes on the median line (Fz, Cz and Pz) one hour after random, double-blind and crossed administration of placebo (P), 3 mg of bromazepam (B3) or 6 mg of bromazepam (B6) on different days. STATISTICS: one-way ANOVA and Post Hoc Scheffé. RESULTS: No significant differences were observed in the RT. At Pz, the CNV amplitudes displayed significant differences for P, B3 and B6 (p = 0.006), and also for B3 and B6 (p = 0.018), with B6 > B3 = P. At Fz, a non-significant tendency (p = 0.074) suggested a difference between the latencies, shorter in B6 than in B3 (p = 0.098), both equivalent to placebo. The mean amplitudes ranged between 2.4 and 5.9 microV. CONCLUSIONS: Behavioural and neurophysiological neurotoxicity was insignificant one hour after administration of a single 3 or 6 mg dose of bromazepam in healthy young adults. Low mean amplitudes were compatible with the interference from distractors and did not result in floor effect.

Effects of caffeine on the electrophysiological, cognitive and motor responses of the central nervous system.

Caffeine is the most consumed psychoactive substance in the world. The effects of caffeine have been studied using cognitive and motor measures, quantitative electroencephalography (qEEG) and event-related potentials. However, these methods are not usually employed in combination, a fact that impairs the interpretation of the results. The objective of the present study was to analyze changes in electrophysiological, cognitive and motor variables with the ingestion of caffeine, and to relate central to peripheral responses. For this purpose we recorded event-related potentials and eyes-closed, resting EEG, applied the Stroop test, and measured reaction time. Fifteen volunteers took caffeine (400 mg) or placebo in a randomized, crossover, double-blind design. A significant reduction of alpha absolute power over the entire scalp and of P300 latency at the Fz electrode were observed after caffeine ingestion. These results are consistent with a stimulatory effect of caffeine, although there was no change in the attention (Stroop) test or in reaction time. The qEEG seems to be the most sensitive index of the changes produced by caffeine in the central nervous system since it proved to be capable of detecting changes that were not evident in the tests of cognitive or motor performance.

Effects of caffeine on the electrophysiological, cognitive and motor responses of the central nervous system

Caffeine is the most consumed psychoactive substance in the world. The effects of caffeine have been studied using cognitive and motor measures, quantitative electroencephalography (qEEG) and event-related potentials. However, these methods are not usually employed in combination, a fact that impairs the interpretation of the results. The objective of the present study was to analyze changes in electrophysiological, cognitive and motor variables with the ingestion of caffeine, and to relate central to peripheral responses. For this purpose we recorded event-related potentials and eyes-closed, resting EEG, applied the Stroop test, and measured reaction time. Fifteen volunteers took caffeine (400 mg) or placebo in a randomized, crossover, double-blind design. A significant reduction of alpha absolute power over the entire scalp and of P300 latency at the Fz electrode were observed after caffeine ingestion. These results are consistent with a stimulatory effect of caffeine, although there was no change in the attention (Stroop) test or in reaction time. The qEEG seems to be the most sensitive index of the changes produced by caffeine in the central nervous system since it proved to be capable of detecting changes that were not evident in the tests of cognitive or motor performance.

Diagnostico diferencial entre Esquizofrenia e Depressäo Maior utilizando a elentroencefalografia quantitativa (EEGq) / Differential diagnosis between Schizophrenia and Major Depression using Quantitative Electroencephalography (QEEG)

A sensibilidade da eletroencefalografia em detectar correlatos de disturbios psiquiatricos aaumentou com o advento de metodos quantitativos de analise (EEGq). parametros quantitativos säo extraídos de, pelo menos, dois minutos de registro EEGrafico, livres de artefato, ao repouso vigil e com as palpebras cerradas, com transformaçäo logarítmica para a obtençäo da Gaussianidade, submetidos a regressäo relativa a idade e transformados em escores Z. Um pequeno subgrupo de parametros da EEGq foi utilizado na construçäo de funçoes classificatorias. O presente estudo, ao utilizar este metodo, demonstrou uma alta precisäo, numa replicaçäo independente, em separar esquizofrenia de depressäo maior

[Quantitative electroencephalography in obsessive-compulsive disorder: preliminary results]. / Eletrencefalografia quantitativa no transtorno obsessivo-compulsivo: resultados preliminares.

The predictive value of quantitative electroencephalography (EEGq) was investigated with regard to the pharmacological treatment of 10 non-medicated obsessive-compulsive disorder (OCD) patients diagnosed according to DSM-IV criteria. The following variables were selected: bipolar relative power in alpha band for Cz-C3, Cz-C4, T3-T5, T4-T6, T3-F7 and T4-F8; bipolar relative power in theta band for Cz-C3, Cz-C4, T3-T5, T4-T6, T3-F7 and T4-F8; and monopolar relative power in theta band for Fp1, Fp2, F7, F3, Fz, F4 and F8. There was statistically significant deviations in five patients with regard to bipolar relative power in alpha band for central regions when compared to normative data bank (control group). This group of patients had a significantly lower age of OCD onset and worse response to pharmacotherapy with serotonin reuptake inhibitors.

Açäo dos novos antipsicóticos sobre o humor em esquizofrênicos / Action of the new antipsychotic drugs on humor in schizophrenic patients

O autor faz uma breve revisao da açao dos novos antipsicóticos sobre o humor em pacientes esquizofrênicos, com base em seus mecanismos de açao ao nível sináptico. Aponta, também, para o diagnóstico diferencial entre depressao, de um lado, e sintomas negativos e distúrbios extrapiramidais, de outro.

Aplicaçäo clínica do mapeamento cerebral no domínio do tempo / Clinical application of brain mapping in Time Domain

O autor descreve as vantagens do Mapeamento Cerebral, no Domínio do Tempo, das Epilepsias em comparaçäo com o Método da Eletroencefalografia Convencional.