Papel do córtex pré-frontal medial na compreensão da linguagem figurada: experimento com eletroencefalografia e estimulação cerebral não-invasiva

A ironia verbal é uma forma figurada de comunicação entre seres humanos, para compreendê-la é fundamental a habilidade de inferir e predizer a intenção daquele que emite a ironia a chamada Teoria da Mente. Atualmente as pesquisas com técnicas de correlação espacial evidenciaram a ativação do Córtex Pré-frontal Medial (CPFM) na compreensão de ironia. Sendo assim, a presente dissertação teve como objetivo investigar o papel dessa estrutura na compreensão da ironia. Para isso, foi utilizada a técnica de Estimulação transcraniana por corrente contínua (ETCC), ou seja, a indução de corrente elétrica de baixa intensidade sobre estruturas corticais específicas. Os efeitos dessa estimulação dependem da polaridade da corrente, e desta forma, é possível verificar como a modulação da área-alvo interfere no desempenho em uma tarefa cognitiva. Sendo assim, foram recrutados 60 participantes de pesquisa, que deveriam ser destros e estarem de acordo com os critérios de inclusão. Eles foram alocados em um dos três grupos de estimulação (anódica, catódica ou placebo), e receberam a ETCC por vinte minutos em CPFM. Após esta fase, os participantes realizaram um teste de compreensão de ironia verbal, com 204 histórias apresentadas visualmente. Esta fase foi realizada durante o registro eletroencefalográfico (EEG) dos participantes. Desta forma, os efeitos da ETCC em CPFM foram verificados: i. no desempenho comportamental no teste (mensurado pelo total de acertos e média de tempo de reação/resposta); ii. assim como na atividade cerebral subjacente a tarefa (mensurada pelos Potenciais evocados relacionados a evento ERP N400 e P600). Os resultados indicam o envolvimento do CPFM na integração semântica de aspectos afetivos da linguagem figurada. O aumento da excitabilidade cortical desta área (estimulação anódica) resultou em uma menor demanda cognitiva para integrar estes aspectos, além disso, diminuiu o tempo de resposta para as incongruências semânticas. Desta forma, entende-se que a compreensão da ironia depende da integração de informações: cognitivas e afetivas. E para que haja a verdadeira apreciação de seu significado é necessário o desenvolvimento de habilidades linguísticas e de Teoria da Mente.Verbal irony is a figurative form of communication between human beings, to understand it a specific ability to infer and predict the ironist intention is essential called Theory of Mind. Currently researches using spatial correlation techniques showed activation of the Medial Prefrontal Cortex (MPFC) on irony comprehension tasks. Thus, this thesis aimed to investigate the role of this area irony comprehension. Therefore the Transcranial direct current stimulation (tDCS) was used, i.e. the induction of low intensity electric current on specific cortical structures. The effects of stimulation depend on the current polarity, and thus, it is possible to investigate how the modulation of target area affects the performance in a cognitive task. Thus, 60 participants were recruited; they were all right handed and match the inclusion criteria. They were allocated to one of three groups of stimulation (anode, cathode or placebo), and received the tDCS for twenty minutes over the MPFC. After, the participants performed a test of verbal irony comprehension, with 204 stories visually presented. This phase was conducted during the EEG recording of the participants. Thus, the effects of tDCS over MPFC were accessed by: i. the behavioral test performance (measured by total score and average reaction time); ii. the brain activity underlying the task (measured by event-related evoked potentials - ERP - N400 and P600). The results indicate the involvement of the MPFC in semantic integration of affective aspects of figurative language. The increased cortical excitability of the area (anodal stimulation) resulted in a decrease of cognitive demand to integrate these aspects; in addition, it decreased the reaction time for the semantic incongruences. Thus, our results indicate that irony comprehension depends on the integration of information: cognitive and affective. Hence for a true appreciation of it s meaning is necessary to develop language skills as well the Theory of Mind.Coordenação de Aperfeiçoamento de Pessoal de Nível Superio

Medial prefrontal cortex stimulation modulates irony processing as indexed by the N400

In this study, we investigated whether the ERP responses observed during a verbal irony comprehension task might represent the cortical manifestation of the Medial Prefrontal Cortex (MPFC) activity. We performed a tDCS-EEG study in which we analyzed the effects of tDCS polarities (anode, cathode, sham) over the MPFC during a verbal irony task. We presented visual short stories portraying everyday situations followed by written statements in either an ironic or literal condition, whose meaning was referred to in the previous context. We manipulated the valence of the stimuli by presenting positive sentences or negative sentences in the ironic and literal conditions. The results revealed that the participants who received the anodal stimulation showed no differences in the N400 amplitude in response to the literal and the ironic condition. This could suggest that anodal stimulation has modulatory effects on N400 responses during irony comprehension. Our results indicated that the MPFC might be critical in accessing ironic information at the initial stage of irony comprehension. Finally, we found that the ironic compliments were more difficult to understand compared to the literal ones, suggesting that irony comprehension is affected by the valence of the information presented

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field