Influência do tratamento crônico com cafeína em modelos animais de esquizofrenia : parâmetros cognitivos e comportamentais

A esquizofrenia envolve um conjunto de sintomas de sensopercepção, cognição e afeto que compromete significativamente a vida do sujeito. O mais aceito modelo para se entender essa doença é o modelo de hiperatividade dopaminérgica, pois drogas como anfetamina e cocaína, que aumentam a atividade dopaminérgica, mimetizam alguns sintomas dessa patologia, e os fármacos usados para o tratamento são os que bloqueiam os receptores de dopamina. Além da dopamina, o sistema glutamatérgico também tem sido relacionado à esquizofrenia, pelo fato de antagonistas de receptores glutamatérgicos do tipo NMDA, tais como PCP, MK-801 e cetamina, provocarem alguns sintomas dessa doença, como desorganização cognitiva e delírios em pessoas saudáveis. adenosina, por sua vez, desempenha um papel neuromodulatório tanto da atividade dopaminérgica quanto da atividade glutamatérgica, inibindo o tônus de ambos neurotransmissores por diferentes vias. Assim, sugerimos que antagonistas de receptores adenosinérgicos, como a cafeína, também seriam um modelo farmacológico para a doença. Com base nisso, demonstramos previamente que camundongos tratados cronicamente com cafeína desenvolvem tolerância cruzada ao efeito do antagonista NMDA MK-801 em provocar hiperlocomoção, mas não em seu déficit cognitivo na esquiva inibitória. Buscando ampliar e melhor caracterizar essa interação, os seguintes parâmetros foram avaliados em camundongos: atividade locomotora realizando-se as curvas de dose e de tempo; memória de trabalho, avaliada na tarefa de alternação tardia; memória de longa duração, avaliada na tarefa de esquiva inibitória e a avaliação de ataxia. Os resultados nos mostraram que camundongos subcronicamente tratados com cafeína na bebida (1 mg/mL, por 1, 3, ou 7 dias) apresentaram habituação semelhante entre os grupos e que MK-801 (0,25 mg/kg, i.p.) produziu hiperlocomoção nos animais tratados com água e 1 dia de cafeína, com efeito diminuído depois de 3 dias e praticamente abolido depois de 7 dias. Depois de 7 dias, o efeito também foi dose-dependente, sem tolerância cruzada na dose de 0,1 mg/mL, intermediária na dose de 0,3 mg/mL e total a 1,0 mg/mL. Os escores de ataxia induzidos por 0,5 mg/kg de MK-801 não foram afetados pelo tratamento com cafeína por 7 dias a 1 mg/mL, mas uma hiperlocomoção transitória foi observada. O tratamento com cafeína por 7 dias a 1 mg/mL preveniu os déficits induzidos por 0,01 mg/kg de MK-801 na tarefa de esquiva inibitória e os atenuou, a 0,4 mg/kg de MK-801, na tarefa de alternação tardia, no labirinto em T. Conclui-se, então, que a hiperlocomoção e os déficits cognitivos – mas não a ataxia – induzidos por MK-801 podem estar influenciados pela atividade reduzida da adenosina. Assim, os estudos sobre a ação da adenosina podem se fazer relevantes para a melhor compreensão da neurobiologia da esquizofrenia. Estes resultados são concordantes com o novo modelo proposto, que é o de hipofunção adenosinérgica na esquizofrenia.

Selective Coupling between Theta Phase and Neocortical Fast Gamma Oscillations during REM-Sleep in Mice

TORT, A. B. L. ; SCHEFFER-TEIXEIRA, R ; Souza, B.C. ; DRAGUHN, A. ; BRANKACK, J. . Theta-associated high-frequency oscillations (110-160 Hz) in the hippocampus and neocortex. Progress in Neurobiology , v. 100, p. 1-14, 2013.

Neurobiology and clinical implications of lucid dreaming

Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states.

Subtle Cognitive Deficits in Adults With a Previous History of Sydenham's Chorea During Childhood

Objective. To evaluate the neuropsychological profile and health-related quality of life (HRQOL) of adults who had rheumatic fever (RF) during childhood with and without Sydenham's chorea (SC).Methods. Three groups of patients were assessed: adults who had RF with SC during childhood (SC group), adults who had RF without SC during childhood (RF group), and controls (CT group). A range of neuropsychological tests looked at several cognitive domains. HRQOL was measured through a Brazilian version of the Short Form 36 (SF-36) health survey.Results. Twenty patients were included in the SC group, 23 patients in the RF group, and 19 patients in the CT group. The 3 groups were homogeneous regarding sex (P = 0.078), age (P = 0.799), schooling (P = 0.600), socioeconomic status (P = 0.138), intelligence quotient (P = 0.329), and scores for anxiety (P = 0.156) and depression (P = 0.076). The SC group demonstrated inferior performance in tests that assessed attention (Digit Span Forward [ P = 0.005], Corsi Block Forward [ P = 0.014]), speeded information processing (Trail Making A [ P = 0.009], Symbol Search [ P = 0.042]), and executive functions and working memory (Corsi Block Backward [ P = 0.028]), and higher scores for attention deficit scale (P = 0.030) when compared with the RF and CT groups. They also showed a tendency toward lower scores in the physical aspects, vitality, emotional aspects, and mental health domains of the SF-36. The RF group had a lower score for the general health domain than the CT group (P = 0.030).Conclusion. Patients who had SC during childhood can exhibit inferior performance in tasks that evaluate attention, speeded information processing, executive functions, and working memory in adult life. Therefore, there is indirect evidence of the persistence of dysfunction in cerebral circuits involved with the basal ganglia. They also presented a worse self-evaluation in HRQOL that was not related to cognitive impairments.

A memória de curto prazo e a síndrome de down: a relação entre contextos de desenvolvimento

Down syndrome (DS) is one of the most frequent causes of intellectual disability, affecting one in every 600 to 1000 live births. Studies have demonstrated that people with DS have a lower capacity for short-term memory (STM) and working memory (WM), which affects their capability to learn new words and to follow spoken instructions, specially when they involve multiple information or consecutive orders/orientations. It seems that the basis of the learning process, as it happens with language and mathematics comprehension and reasoning, relies in the STM and WM systems. Individuals with DS are increasingly included in mainstream education, and yet, very few researches have been conducted to investigate the influence of memory development and the type of enrollment (regular school and special school). This study investigated the relationship between the type of school enrollment with the performance on STM tests and also, the relationship of this performance with early stimulation (ES). The tests used in the first research were the digit span, free recall, word recognition and subtests of the Wechsler Intelligence Scale for Children Third Edition (WISC-III). Individuals enrolled in the regular schools group had higher scores on the digit span test and the subtests of the WISC-III. In the free recall and recognition tests, no differences were found. This study indicates that the type of enrollment might influence the memory development of individuals with DS and clearly points the need for future investigations. In the second research, the tests used were the digit span, free word recall and subtests of the WISC-III. The test results showed better performance by adults that received ES before six months of age. The studies showed improvement in STM both in people who attended or were attending regular school, as well as those who benefited from ES before six months of age. However, some issues still need to be better understood. What is the relation between this stimulation with the individual s education? Since ES may reflect a greater family involvement with the individual, what is the role of emotional components derived from this involvement in the cognitive improvement? These and other questions are part of the continuity of this study

Efeitos dos esteroides anabólicos androgênicos sobre funções cognitivas de ratos

The use and the demand for substances that enhance masculinity, strength and sexual power are not novel. Over the years, this search has assisted the research directions in this area, leading to the discovery of the primary male sex hormone testosterone in 1935. Since then, numerous testosterone analogue compounds were synthesized, which are generically called Anabolic Androgenic Steroids (AAS). The AAS were produced for therapeutic purposes, but an increase in the use of these compounds for other purposes occurred over time. Initially they were used mainly to improve performance in athletes. However, recent studies have shown that the use of AAS by non-athletes with aesthetical purposes have been increasing as well. The abuse of AAS with non-clinical purposes can promote a number of physiological alterations, such as heart, liver, respiratory and psychological problems such as changes in mood, levels of anxiety and aggression. Exposure to supraphysiological doses of AAS is associated with behavioral changes, however, little is known about the effects of AAS on cognitive functions. In this work, we aimed to mimic the AAS abuse in humans with intramuscular administration of a supraphysiological dose of testosterone propionate (TP) in rats. We investigated the effects of this treatment on different aspects of cognitive function, specifically learning, memory and anxiety. Adult male Wistar rats were tested in the spontaneous alternation, novel object recognition and plus-maze discriminative avoidance tasks. The control group received intramuscular injections of vegetable oil (vehicle), and the TP group received injections of TP (10 mg/kg, i.m.). The injections were administered for 40 days, with intervals of 48 hours (chronic treatment) or in a single injection (acute treatment). In addition to the behavioral assessments, we performed biochemical analyzes as indicators of the endocrine effects of the treatment. Our results show that chronic treatment with a supraphysiological dose of TP caused memory impairments in the novel object recognition and the discriminative avoidance tasks. The spatial working memory (evaluated by spontaneous alternation task) was not affected. Also, we did not observe changes in anxiety levels. Regarding the biochemical parameters, chronic treatment increased serum levels of glutamicpyruvic transaminase, an indicator of hepatic and pancreatic lesions (as those observed after chronic use of these substances in humans). On the other hand, acute treatment with PT did not promote significant changes in any of these parameters when compared to the control group. In summary, we conclude that chronic treatment with a supraphysiological dose of testosterone propionate produces memory deficits in novel object recognition and retrieval of the discriminative avoidance task in adult male rats

Déficits de memória induzidos por baixas doses de reserpina em ratos: possível relação com prejuízos no processamento emocional na Doença de Parkinson

We have recently verified that the monoamine depleting drug reserpine at doses that do not modify motor function - impairs memory in a rodent model of aversive discrimination. In this study, the effects of reserpine (0.1-0.5 mg/kg) on the performance of rats in object recognition, spatial working memory (spontaneous alternation) and emotional memory (contextual freezing conditioning) tasks were investigated. While object recognition and spontaneous alternation behavior were not affected by reserpine treatment, contextual fear conditioning was impaired. Together with previous studies, these results suggest that mild monoamine depletion would preferentially induce deficits in tasks involved with emotional contexts. Possible relationships with cognitive and emotional processing deficits in Parkinson disease are discussed

A influência da prática meditativa sobre parâmetros psicofisiológicos e tarefas de memória operacional em indivíduos saudáveis

Meditation is described as a method for improving attention and promoting psychological and emotional stability, presenting favourable results on memory and stress tolerance as well. Studies have shown differences in physiological and psychological measurements between meditators and non-meditators. The aim of this study was to investigate the influence of regular meditation practice on working memory, psychological measurements and quality of life of healthy practitioners. We carried out a comparative study with meditators and non-meditators. Working memory tests and standard inventories of life quality, anxiety, mood, sleep quality, depression and stress were applied. Our study showed that meditators presented better scores in parameters indicative of life quality, mood, depression and stress when compared with non-meditators. Moreover, there was a trend in best performance of meditators in memory tasks (forward digit span task and Hanoi tower). These findings corroborate other studies showing that regular meditation can provide an improvement in general quality of life and affecting positively the behavioral and attentional functions in individuals

Proposta de Intervenção para Auxiliar a Reabilitação Motora e Cognitiva de Pacientes com Acidente Vascular Cerebral

Stroke is the leading cause of combined motor and cognitive disability worldwide. The rehabilitation of stroke patients is mostly directed towards motor recovery through the training of the affected member under supervision of a Physical Therapist. In the present study we introduce a new approach for both cognitive and motor therapy, which relies on motor imagery of the upper limbs and working memory training. This therapy should be utilized as an adjuvant to physical therapy. Ten individuals (5 men and 5 women) were selected for the pilot study, all of them in the acute phase of the first ischemic stroke episode. The control group had 5 individuals who were submitted to physical therapy only, whilst the other 5 patients in the experimental group also performed the cognitive and motor training with a video game specially built for this study. Two patients left the experimental group before the end. Total training lasted for 9 weeks, 2 times a week, for half an hour. Patients reported they enjoyed playing the game, even though it required a lot of mental effort, according to them. Plus, they considered it had a beneficial influence in their activities of daily living. No side effects were reported. Preliminary results suggest there is a difference between groups in cognitive and upper limb motor evaluation following the intervention. It is important to notice that our conclusions are limited due the small sample number. Overall, this work is supported by other studies in literature focused in rehabilitation with motor imagery and working memory and indicate a continuity of the research, increasing total training hours

Alterações cognitivas em ratos infectados com Toxoplasma gondii

Toxoplasma gondii is a protozoan parasite that induces behavioral changes in rodents. The aim of this study was to evaluate the effect of infection by T. gondii during the chronic phase in working memory and impulsivity in rodents as well as the effect of antipsychotics to reverse any behavioral changes resulting from infection. Female Wistar rats (n = 40) were infected with 25 cysts of the strain ME-49 T. gondii after 4 months the animals were subjected to behavioral tests: tolerance to delay gratification, in which the animal must choose between two rewards, a smaller and more immediate, but delayed and the test of spontaneous alternation, in which the animal must use spatial cues to remember previously visited arms. Antipsychotic drugs were intraperitoneally administered during the testing of the behavioral experiments, the antipsychotic is haloperidol (1.5 mg / kg) administered 60 min before the start of the session and the antipsychotic clozapine (2.5 mg / kg) 30 min before. Animals infected with the parasite did not show operating deficits of memory, and motor impairment did not develop, however motor impairment was observed only in animals treated with haloperidol. It was found that administration of clozapine and haloperidol increased the percentage of alternation in infected and control groups in task switching espontânea.Não no distinction between control animals and infected the test of tolerance to delay gratification in relation to the percentage of choices greatest reward, during the pre-training and training, in which there is a delay of 15 s to access the great reward, however it was observed that infected animals prefer the greatest reward, when there is a delay of 30 s when compared to control group. The administration of clozapine possible that infected animals chose the greatest reward in the delay of 30 seconds during the test. These data suggest that infected mice do not exhibit deficits in working memory and that clozapine has therapeutic efficacy in improving cognitive performance of mice infected

Avaliação da relação entre qualidade de sono e uma intervenção com jogos para o desempenho de crianças e adolescentes

The sleep is an active brain process that allows the efficient realization of daily tasks. The changes on sleep patterns may influence the different cognitive processes performance. Many recent studies show the possibility of cognitive performance improvement, through the cognitive training with the use of computer games. The question is if these interventions may be influenced by the sleep quality. Thus, we evaluated the sleep quality effect about the efficacy of an intervention with computers games based on the working memory and attention for a cognitive performance training of elementary school students. The sample was constituted by 42 students with average age of 10,43 years old (SD=1,23), with 22 male participants and 20 female participants. We used to evaluate the sleep with the parents a sleep questionnaire, a sleep diary and the Sleep Behavior Questionnaire. In regard to intervention, the subjectives were distributed in an experimental and in a control group, both with 21 participants. In the first group occurred the intervention that consisted in the working memory and attention training with two cognitive tasks (Safari e Brain Workshop) during 30 daily minutes, for a 6 weeks period. In an equal period, the students from the control group should reproduce an artwork using drawing software. To evaluate the cognitive performance we applied before and after the intervention period the Wechsler Intelligence Scale for Children (WISC-III). The results showed that in both the groups the performance of the intelligence, working memory, attention and visuospatial skills was below of the mean. The cognitive processes evaluated after of intervention in the experimental group had a performance significantly higher in the Perceptual Reasoning Index (t = -6,24; p < 0,01) and in the Full Scale IQ (t = -5,09; p < 0,01) and Performance IQ (t = -6,52; p < 0,01), suggesting a improvement on the visuospatial skills, attention, working memory and processing speed. On the control group, the performance was significantly higher in the Coding subtest (t = -5,38; p< 0,01) and in the Perceptual Reasoning Index (t = -3,66; p = 0,01), suggesting a improvement on the visuospatial skills and attention. The mean obtained with the Sleep Behavior Questionnaire was 53,76 (SD=14,96) for an experimental group and 61,19 (SD=12,82) for a control group, indicating tendency for a bad sleep quality in that last one. Not only during the first days, but also in the last fifteen days of the intervention we verified in the two groups an adequate time to sleep, duration and regularity, in the weekdays and on the weekends. We didn t find significant differences between the two groups in none of the sleep variables. We verified statistically meaningful improvement on the performance of the experimental group with the intervention in the two games. We didn t verify significant correlations between the games performance index and in the sleep variables of the experimental group individuals. We verified significant correlations among the performance on the Brain Workshop and the Cubes subtest, the Perceptual Reasoning Index and the Scale Performance IQ, suggesting that the significant improvement of the visuospatial skills and of the attention was correlated with the performance in the Brain Workshop. Although the absence of correlations with the performance in the Safari, possibly it also has relieved in the improvement of the cognitive performance. The findings support the hypothesis that the computer games might be a satisfactory tool for the improvement of the performance in visuospatial skills and attention. This can be resulted of the insertion of visuospatial stimulations in the task, for example, graphical elements with thematic for children that increase the interest. The IQ below mean the individuals might have influenced the improvement absence on the cognitive processes like the working memory with games. Moreover, it wasn t verified a relation between the sleep quality and the intervention efficacy. It might have been influenced by the n of the sample. Future studies must focalize in the improvement of the effect of the interventions with games

Discalculia do desenvolvimento: avaliação da representação numérica pela ZAREKI-R

O presente estudo investigou aspectos da representação numérica (processamento numérico e cálculo) e memória operacional de crianças com transtornos de aprendizagem. Participaram 30 crianças de idade entre 9 e 10 anos, ambos os gêneros, divididas em dois grupos: sem dificuldade em aritmética (SDA; N=11) e com dificuldade em aritmética (CDA; N=19), avaliadas pela ZAREKI-R, Matrizes Coloridas de Raven, o Blocos de Corsi e o BCPR. Crianças CDA exibiram escores levemente mais baixos que as SDA quanto ao nível intelectual e nos Blocos de Corsi. Na ZAREKI-R apresentaram prejuízo nos subtestes ditado de números, cálculo mental, problemas aritméticos e total. Crianças CDA apresentaram déficits específicos em memória operacional visuoespacial e comprometimento em processamento numérico e cálculo, compatível com discalculia do desenvolvimento.

Treino musical e capacidade da memória operacional em crianças iniciantes, veteranas e sem conhecimentos musicais

A memória operacional e a atividade musical ativam áreas encefálicas recíprocas e homólogas, contudo não há evidências se o treino musical pode ampliar a capacidade da memória operacional. Objetivo: Avaliar o desempenho do treino musical sob a memória operacional em crianças de 9 e 10 anos de idade, praticantes de treino musical e sem experiência musical. PARTICIPANTES: Crianças Iniciantes (n=20), Veteranas (n=20) e Grupo Controle (n=20). MATERIAIS: Instrumentos computadorizados para avaliação da memória operacional. RESULTADOS: Crianças veteranas apresentaram melhores pontuações no BCPR (Teste de Repetição de Pseudopalavras para crianças brasileiras) e em subtestes da AWMA (Avaliação Automatizada da Memória Operacional). CONCLUSÃO: O treino musical parece ter contribuído para o desenvolvimento da memória operacional em crianças veteranas no programa de treino musical.

The effects of anxiety on visual search, movement kinematics, and performance in table tennis: A test of Eysenck and Calvo's processing efficiency theory

Processing efficiency theory predicts that anxiety reduces the processing capacity of working memory and has detrimental effects on performance. When tasks place little demand on working memory, the negative effects of anxiety can be avoided by increasing effort. Although performance efficiency decreases, there is no change in performance effectiveness. When tasks impose a heavy demand on working memory, however, anxiety leads to decrements in efficiency and effectiveness. These presumptions were tested using a modified table tennis task that placed low (LWM) and high (HWM) demands on working memory. Cognitive anxiety was manipulated through a competitive ranking structure and prize money. Participants' accuracy in hitting concentric circle targets in predetermined sequences was taken as a measure of performance effectiveness, while probe reaction time (PRT), perceived mental effort (RSME), visual search data, and arm kinematics were recorded as measures of efficiency. Anxiety had a negative effect on performance effectiveness in both LWM and HWM tasks. There was an increase in frequency of gaze and in PRT and RSME values in both tasks under high vs. low anxiety conditions, implying decrements in performance efficiency. However, participants spent more time tracking the ball in the HWM task and employed a shorter tau margin when anxious. Although anxiety impaired performance effectiveness and efficiency, decrements in efficiency were more pronounced in the HWM task than in the LWM task, providing support for processing efficiency theory.

Desempenho em consciência fonológica, memória operacional, leitura e escrita na dislexia familial

Background: familial dyslexia. Aim: to characterize and compare the phonological awareness, working memory, reading and writing abilities of individuals whose family members are also affected. Method: in this study 10 familial nuclei of natural family relationship of individuals with dyslexia were analyzed. Families of natural individuals living in the west region of the state of São Paulo were selected. Inclusion criteria were: to be a native speaker of the Brazilian Portuguese language, to have 8 years of age or more, to present positive familial history for learning disabilities, That is, to present at least one relative with difficulties in learning. Exclusion criteria were: to present any neurological disorder genetically caused or not, in any of the family members, such as dystonia, extra pyramidal diseases, mental disorder, epilepsy, attention deficit and hyperactivity disorder (ADHA); psychiatric symptoms or conditions; or any other pertinent conditions that could cause errors in the diagnosis. As for the diagnosis of developmental dyslexia, information about the familial history of the adolescents and children was gathered with the parents, so that a detailed pedigree could be delineated. Neurological, psychological, speech-language, and school performance evaluations were made with the individuals and their families. Results: the results of this study suggest that the dyslexic individuals and their respective relatives, also with dyslexia, presented lower performances than the control group in terms of rapid automatic naming, reading, writing and phonological awareness. Conclusion: deficits in phonological awareness, working memory, reading and writing seem to have genetic susceptibility that possibly determine, when in interaction with the environment, the manifestation of dyslexia.