Functional neuroimaging research on language recovery in patients with aphasia due to left hemisphere damage has generated some intriguing results. However, it is still not clear what role the right hemisphere plays in supporting language functions in chronic phase for patients with different site and size of lesion when different tasks are used. The present study was aimed at exploring the role of perilesional, ipsilesional and contralesional regions in neural recovery in participants with aphasia with different site and size of lesion using three different language tasks. All patients in the present study were in the chronic stage who had achieved high levels of recovery. Functional magnetic resonance imaging (fMRI) was used to characterize cortical activation in eight stroke patients and eight age/gender matched controls during lexical decision, semantic judgment and picture naming. An event related design using jittered interstimulus intervals (ISIs) was employed to present the stimuli. The fMRI scans revealed differences in activation patterns across the three tasks. Normal control participants and participants with aphasia mainly activated the left perisylvian region during the lexical decision task and the semantic judgment task. However, during the picture naming task, all participants activated bilateral posterior regions irrespective of the site or size of lesion. Subsequent regions of interest analysis and laterality index analysis revealed that patients with larger lesions produced greater right hemisphere activation than patients with smaller lesions during the picture naming task. The results of this study demonstrate that recovery is task, lesion site and lesion size specific. Further, the findings of the present study indicate a role for both homologous contralesional cortex and perilesional and ipsilesional regions as efficient mechanisms for supporting language functions in chronic stroke patients. / text

Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are chronic, debilitating illnesses. Impairments in cognitive processes such as social cognition, episodic simulation, and neuropsychological performance have been documented separately in both disorders. Despite our increasing knowledge of these impairments, the potential underlying transdiagnostic mechanisms remain relatively unexplored. This thesis examines correlates of these processes in persons with a primary diagnosis of MDD with a history of trauma exposure, and in persons with PTSD. The first study examined the association between the social cognitive domain of empathy and parental bonding in women with PTSD associated with childhood abuse. Participants with PTSD reported altered levels of cognitive and affective empathy, compared to controls. Paternal care during childhood was the only predictor of cognitive empathy (i.e., perspective taking). The second study investigated the specificity of episodic simulation of future positive, negative, and neutral events in relation to parental bonding and neuropsychological functioning among participants with MDD. Optimal parental bonding and higher scores on measures of neuropsychological functioning were associated with increased specificity of episodic simulation. In the third study, we examined the relation between dissociative symptoms and neuropsychological functioning in participants with MDD. Patients with MDD report significantly higher levels of dissociation as compared to controls, and more severe dissociation was related to poorer neuropsychological performance among this patient group. Lastly, using independent component analysis of resting-state fMRI data, the fourth study examined the association between intrinsic connectivity networks and neuropsychological performance among participants with MDD. Connectivity within the default mode, salience, and central executive networks was associated with neuropsychological and clinical (i.e., depression, dissociation, PTSD) variables. Overall, this thesis demonstrates that variables such as parental attachment, dissociation, and intrinsic connectivity networks may underlie some of the alterations in cognitive processes seen in MDD and trauma-related disorders. / Dissertation / Doctor of Philosophy (PhD) / Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) negatively affect quality of life and day-to-day functioning. These populations show difficulties in domains related to cognitive processing, such as empathy, imagining future events, and neuropsychological functioning (e.g., memory and attention). This thesis focuses on examining variables that may be related to these difficulties. In particular, we study developmental variables, such as parental bonding, clinical symptoms, such as dissociation, and neuroimaging data. Our findings suggest that these variables are all related to impairments in different areas of cognitive processing. By understanding what may be contributing to these cognitive difficulties, we may be able to design treatment strategies that target the underlying causes of these difficulties.

It is well known that music can influence our emotions. Research on mind-wandering has revealed that our emotional state can influence the valence of thought content and the prevalence of mind-wandering. Recent behavioural studies have suggested that music can modulate mind-wandering. However, the neural mechanisms to support the claims are unknown. This thesis aim was to explore how music can modulate mind-wandering by reviewing functional neuroimaging studies on the topic. The findings suggest that music induces mind-wandering as it engages the default mode network in a similar fashion that resting does. Music-induced activity from the orbitofrontal cortex and the posterior cingulate cortex seems to be a good neural indicator for mind-wandering content that has a negative valence.

How is information organized in the brain during natural reading? Where and when do the required processes occur, such as the perception of individual words and the construction of sentence meanings. How are semantics, syntax and higher-level narrative structure represented? Answering these questions is core to understanding how the brain processes language and organizes complex information. However, due to the complexity of language processing, most brain imaging studies focus only on one of these questions using highly controlled stimuli which may not generalize beyond the experimental setting. This thesis proposes an alternative framework to study language processing. We acquire data using a naturalistic reading paradigm, annotate the presented text using natural language processing tools and predict brain activity with machine learning techniques. Finally, statistical testing is used to form rigorous conclusions. We also suggest the use of direct non-parametric hypothesis tests that do not rely on any model assumptions, and therefore do not suffer from model misspecification. Using our framework, we construct a brain reading map from functional magnetic resonance imaging data of subjects reading a chapter of a popular book. This map represents regions that our model reveals to be representing syntactic, semantic, visual and narrative information. Using this single experiment, our approach replicates many results from a wide range of classical studies that each focus on one aspect of language processing. We extend our brain reading map to include temporal dynamics as well as spatial information by using magnetoencephalography. We obtain a spatio-temporal picture of how successive words are processed by the brain. We show the progressive perception of each word in a posterior to anterior fashion. For each region along this pathway we show a differentiation of the word properties that best explain its activity.

Apesar das evidências a favor da automaticidade no processamento de estímulos aversivos, especialmente na amígdala, a sua resposta parece ser dependente da disponibilidade de re- cursos atentivos. Dessa forma, a atenção pode atuar como um mecanismo de regulação emocional, importante para a compreensão de uma série de distúrbios psiquiátricos em que este mecanismo está prejudicado. Nesse estudo, investigamos o processo do regulação e- mocional pela atenção sob uma condição de grande demanda atentiva e com estímulos altamente aversivos. Imagens funcionais por ressonância magnética foram adquiridas de 22 voluntários saudáveis enquanto figuras emocionais (IAPS - International Afective Picture System), neutras e aversivas (corpos mutilados) eram apresentadas enquanto eles realiza- vam três tarefas diferentes, em que a atenção era manipulada. As imagens foram apresenta- das no centro do campo visual, enquanto apareciam duas barras, uma de cada lado da figu- ra. As três tarefas atentivas correspondiam a reconhecer: (1) a valência emocional da figura, (2) a semelhança na orientação das duas barras com diferenças de 0º ou 90º (tarefa fácil) e (3) a semelhança das mesmas com diferença de 0º ou apenas 6º (tarefa muito difícil). Nas análises de regiões de interesse (ROIs) observamos um padrão de regulação emocional, com dimuição da amplitude do sinal BOLD estimado, nas regiões da amígdala, ínsula ante- rior, cíngulo posterior e córtex pré-frontal medial, ventrolateral e orbitofrontal na tarefa fácil. Já na tarefa difícil, esse comportamento se manteve, com excessão do sinal da ínsula e do orbitofrontal, que voltou a subir, talvez, por um efeito de estresse. Verificamos uma maior amplitude do sinal BOLD na região dos córtices pré-frontal dorsolateral, parietal superior e área motora suplementar quando a atenção foi alocada para as tarefas de barras, supostamente, por um efeito da demanda maior de atenção. Nestes resultados, todo um conjunto de estruturas envolvidas no processamento emocional foi regulado pela manipu- lação da atenção nas tarefas. Também observamos uma correlação entre o traço de afeto positivo dos sujeitos e a estimativa do sinal BOLD da amígdala sob a regulação emocional. Estas evidências indicam que, mesmo para estímulos extremamente negativos, a disponibi- lidade de recursos de atenção e, talvez, mecanismos inibitório de controle cognitivos sobre a amígdala sejam fatores condicionantes da resposta emocional. / Because of the biological significance of motional stimuli, their processing is considered largely automatic. However, there are also evidences that processing of emotional stimuli requires some level of attention. Higher attention demands in a task may limit emotional processing which can be interpreted as an emotion regulation strategy. Our experiments utilized highly demanding attention task while also highly aversive and arousing visual stimuli comprising mutilated bodies is presented. The experiment employed a single task, which consisted of determining whether two peripheral bars were like oriented or not, such to evaluate further brain mechanisms involved in emotion regulation by functional mag- netic resonance imaging (fMRI). Our results revealed that task-irrelevant unpleasant images slowed reaction time during the performance of the main easy task, but not at highly de- manding one which is suggesting of emotion suppression. Such modulatory effect was also revealed by ROI analysis showing that many brain regions, including regions of amygdala, anterior insula, posterior cingulate, and medial, ventrolateral and orbitofrontal prefrontal cortex have their processing of emotional visual stimuli reduced by attentional manipula- tions while there were BOLD signal increases in dorsolateral prefrontal and superior parie- tal cortex respective to attention demand. These results suggest that attentional manipula- tions that more fully consume attentional resources in order to demonstrate that the proc- essing of emotional stimuli is limited.

Introdução: Déficits de memória episódica constituem o marcador cognitivo mais frequente em pacientes com Comprometimento Cognitivo Leve (CCL).Estudos prévios mostram que déficits de memória episódica podem ser minimizados nestes pacientes por intervenções comportamentais. Entretanto, os mecanismos cerebrais envolvidos nos efeitos do treino cognitivo ainda são pouco explorados. O objetivo deste estudo foi avaliar o correlato neural por ressonância magnética funcional de um treino breve de memória em pacientes com CCL e compará-los com os achados em idosos saudáveis. Foram avaliados 18 pacientes com CCL e 19 idosos controles com a utilização de ressonância magnética funcional (RMf) em uma tarefa de codificação de listas de palavras com diferentes graus de relação semântica antes e após uma sessão de treino de estratégias de memória. Na sessão pré-treino, os participantes foram instruídos a memorizar as palavras durante a sessão de RMf sem qualquer orientação sobre o uso de estratégias de codificação. Após um treino breve no qual estratégias específicas de organização e agrupamento semântico foram exercitadas, os sujeitos foram reconduzidos ao aparelho de ressonância magnética e realizaram a sessão pós-treino, na qual foram instruídos a utilizar a estratégia treinada durante o paradigma de codificação de palavras. Os resultados dos exames de ressonância magnética funcional foram processados e analisados com o programa FSL versão 4.1. Ambos os grupos apresentaram aumento no número de palavras evocadas associado ao uso da estratégia treinada. Em ambos os grupos foi observado um aumento do sinal BOLD após o treino em regiões do córtex pré-frontal dorsolateral esquerdo e do córtex parietal bilateral. No grupo de idosos controles, entretanto, foi observada também uma redução da ativação em regiões do córtex parietal posterior esquerdo e cíngulo posterior bilateral, do córtex pré-frontal medial e cíngulo anterior direitos, do lóbulo parietal inferior e do córtex temporal superior direitos, do córtex pré-frontal dorsolateral direiro e do córtex óribito-frontal bilateral. A interação grupo x tempo foi significativa em áreas do córtex pré-frontal dorsolateral e ventromedial direitos. Estes resultado indicam que existem diferenças no recrutamento de regiões pré-frontais em resposta ao uso de estratégias de codificação em paradigmas de codificação de palavras entre pacientes com CCL e idosos cognitivamente saudáveis / The present studyinvestigated the effects of different applicationsof verbal learning strategies duringepisodicmemory encoding in patients with Mild Cognitive Impairment (MCI) (n=18) and normal controls (n=17) using functional magnetic resonance imaging (fMRI).The main goal of this study was to verify whether externally guided increases in verbal learning strategy application during episodic memory encoding modulate brain activity in memory-related networks in the same level in MCI as in controls. Participantswerescanned twice, using a word-list encoding fMRI paradigm.In the first session, self-initiated encoding strategies were used to intentionally memorize words during encoding. In the second session, participants received an explicit instruction to apply a semantic organization strategy (i.e. semantic clustering)to perform the task. The fMRI word list learning paradigm consisted of alternating blocks of encoding and resting baseline conditions. To perform the spontaneous fMRI session, participants were not instructed about the semantic organization of the words in the lists beforehand or given any practice with related lists. Therefore, any grouping by category observed in the subsequent free recall at the end of this fMRI acquisition was presumed to be self-initiated by the subject. At the end of the spontaneous session, each subject received a brief period of guidance or instructions to apply semantic strategies and organize words in terms of semantic categories during encoding, using a new set of word lists. Immediately after practicing the application of the strategy, participants were scanned again using the same type of paradigm as in the first session, except for the use of new set of word lists and the explicit instruction to apply semantic clustering.Free recall and strategic index scores were assessedafter each session. fMRI brain activation and deactivation during encoding of word lists in memory-related networks were examined across sessions. Results from the fMRI analysis revealed that after the explicit orientation to apply the verbal learning strategy, greater recruitment of frontoparietal network regions were observed in both MCI and control groups in relation to the unconstrained encoding condition. Group-differences in functional deactivations, however, were observed in the medial prefrontal (mPFC) cortex and in the right superior frontal gyrus, two critical nodes of the default mode network, related to the absence of modulation in the activity of the mPFC, along with a lack of suppression of the right superior frontal gyrus in MCI, in response to the increased use of the encoding strategy. A different association between improvement in strategy use and session-related changes in activation of the medial orbitalfrontal cortex between groups was also confirmed. That is, improvements in strategy use in controls contribute to a great extent in the amount of deactivation in OFC, whereas in patients, only a small portion of the increase in activation in this region was predicted by increases in strategy application

INTRODUÇÃO: O Doppler Transcraniano funcional pode avaliar mudanças na velocidade do fluxo sanguíneo encefálico associadas a tarefas cognitivas e/ou sensitivo-motoras. Mede de maneira indireta a atividade metabólica de regiões cerebrais, segundo o princípio do acoplamento neurovascular. Os objetivos deste estudo foram: desenvolver um novo método de análise de Doppler transcraniano funcional para análise da lateralização hemisférica e verificar a capacidade deste novo método em diferenciar a lateralização hemisférica durante a execução de uma tarefa motora unimanual por indivíduos saudáveis. Adicionalmente, a lateralização hemisférica foi correlacionada com a preferência manual nestes indivíduos. MÉTODOS: Treze indivíduos saudáveis foram submetidos a um exame de Doppler transcraniano funcional durante uma prova de ativação motora manual (oposição de dedos). As sessões de Doppler transcraniano funcional foram realizadas com aparelho Doppler-Box Transcranial Doppler Unit. A prova manual compreendeu uma sequência de movimentos de oposição do primeiro e segundo dedos (thumb-tofinger opposition movement) realizado por uma mão e depois pela outra, em uma frequência de 1 movimento por segundo (1Hz) fornecida por um metrônomo digital. Durante a execução dos movimentos, foram insonadas simultaneamente as artérias cerebrais médias direita e esquerda. Para interpretação dos dados de Doppler transcraniano funcional desenvolvemos um novo programa de análise denominado FDAT, que tem vantagens de sofrer mínima influência de artefatos de ruído no sinal e de não assumir um formato pré-determinado da resposta hemodinâmica cerebral. Foi calculado um índice de lateralização (IL) como a diferença entre a velocidade relativa média da época de ativação e a velocidade relativa média da época de repouso para cada prova motora. Foi calculada a diferença dos valores de IL (ILe - ILd) provenientes da análise com cada método, obtendo-se um índice de ativação, próprio de cada sujeito. A comparação do índice de ativação durante a movimentação da mão direita, e durante a movimentação da mão esquerda, foi feita com o teste de Wilcoxon. A correlação entre o índice de ativação e a preferência manual avaliada pelo Inventário de Edimburgo foi avaliada pelo coeficiente rho de Spearman. RESULTADOS: Houve uma diferença estatisticamente significante entre o IA obtido durante a movimentação da mão direita ou da mão esquerda (p=0,02). Houve correlação estatisticamente significante entre a preferência manual e a assimetria na lateralização hemisférica identificada pelo Doppler Transcraniano funcional (rho = 0.85, p < 0.001). CONCLUSÕES: A análise do Doppler Transcraniano funcional mostrou-se viável pelo método proposto, capaz de avaliar o grau de lateralização hemisférica em uma prova de ativação motora, com boa correlação com a preferência manual. Trata-se de uma ferramenta prática, não invasiva e de baixo custo para a avaliação da lateralização hemisférica em determinadas provas funcionais / INTRODUCTION: Functional transcranial Doppler is a method for the assessment of changes in blood flow velocity of the middle cerebral artery. An asymmetric increase in blood flow velocity is a marker of hemispheric lateralization during unimanual motor task performance. The aims of this study were to propose a novel and efficient method for functional transcranial Doppler analysis based on cubic smoothing splines, and to verify the ability of this method to identify hemispheric lateralization during unimanual motor task performance in healthy subjects. In addition, hemispheric lateralization was correlated with handedness in these subjects. METHODS: Thirteen healthy subjects participated in the study. Blood flow velocities in the right and left middle cerebral arteries were recorded using functional transcranial Doppler during a finger-tapping task with either the right or left hand. Data were analyzed with a multi-step new method that included: baseline determination, raw data normalization, smoothing, lateralization Index calculation, definition of rest and motor task epochs and activation Index calculation. A positive activation Index reflects right-hemisphere lateralization and a negative activation index, left hemisphere lateralization. RESULTS: There was a statistically significant difference between the activation index obtained during right or left hand movements (p=0.02). Hand dominance was significantly correlated with asymmetry in hemispheric lateralization assessed with functional transcranial Doppler (rho = 0.85, p<0.001). CONCLUSIONS: This novel method for functional transcranial Doppler analysis was capable to assess the hemispheric lateralization during motor task performance, and correlated well with handedness. It is a practical, non-invasive and unexpensive tool for the assessment of hemispheric lateralization.

This study aims to shed light on how and when mechanisms of the human brain evolved to support complex cognition and language. The field of evolutionary cognitive archaeology asserts that prehistoric technologies, as products of past cognition in action, are informative of the minimum cognitive and linguistic abilities that hominins needed to possess for their production. Previous researchers attempted to reconstruct the neural correlates of two Early Stone Age (ESA) tool industries, the 2.6 million-year-old Oldowan industry and the 0.7 million-year-old late Acheulian industry, by using positron emission tomography (PET) to observe the functional activation occurring in the brains of trained and expert stone knappers after making these different tool types. Because of evidence for overlap between the knapping and language circuits of the brain and increased anterior frontal activity during Acheulian tool production, these researchers argued that their results 1) indicate increased cognitive demands for late Acheulian tool production relative to Oldowan tool production and 2) support a technological origin for language, meaning that certain language functions co-opted the neural substrate and functions that were already established for toolmaking and tool use. Because of the motion limiting aspects of PET, however, these studies were unable to record the hemodynamic response of naturalistic stone knapping in real-time. They also were unable to observe the functional activation associated with the earliest stage of learning, which is likely to differ from late stage learning or expertise. Furthermore, any conclusion regarding a technological origin for language is problematic if it relies on data obtained from participants who learned to knap with verbal instruction. To test these two claims, this dissertation utilized a neuroimaging technique called functional near-infrared spectroscopy (fNIRS) to explore the neural correlates of real-time, naturalistic Oldowan and Acheulian stone knapping at three different points in learning. Participants in the study were separated into two groups to learn ESA knapping skills. Both groups watched the same video tutorials that depicted an expert’s hands as he made stone tools, but those in the verbal group heard spoken instructions, while those in the nonverbal group watched a version with the sound turned off. Functional brain images were reconstructed from the digitized landmarks of each participant’s head and from the optical data. An analysis of variance (ANOVA) revealed a clearer distinction between the neural processes of Oldowan and Acheulian tool manufacturing tasks than has previously been demonstrated. Only the Acheulian task recruited a frontotemporal working memory network. Selection for individuals with increased working memory capacities, which would have allowed them to make increasingly complex tools to gain access to novel dietary items, may have spurred the evolution of larger brain size in the genus Homo during the early Pleistocene. The results also demonstrated that the presence or absence of language during training dictated which higher-order cognitive areas of the brain become engaged and at what point in training. Thus, the results of previous neuroarchaeological studies reflect a very specific condition of stone knapping skill acquisition that involves linguistic instruction, which may not be analogous to how skills were transmitted during the ESA. Finally, evidence of overlap between left hemisphere language and stone knapping circuits among the participants in the nonverbal group lends additional support for the technological origin for language hypothesis.

<p>Although consciousness has been studied since ancient time, how the brain implements consciousness is still considered a great mystery by most. This thesis investigates the neural correlates of consciousness by measuring brain activity with functional magnetic resonance imaging (fMRI) while specific contents of consciousness are defined and maintained in various experimental settings. Study 1 showed that the brain works differently when creating a new conscious percept compared to when maintaining the same percept over time. Specifically, sensory and fronto-parietal regions were activated for both conditions but with different activation patterns within these regions. This distinction between creating and maintaining a conscious percept was further supported by Study 2, which in addition showed that there are both differences and similarities in how the brain works when defining a visual compared to an auditory percept. In particular, frontal cortex was commonly activated while posterior cortical activity was modality specific. Study 3 showed that task difficulty influenced the degree of frontal and parietal cortex involvement, such that fronto-parietal activity decreased as a function of ease of identification. This is interpreted as evidence of the non-necessity of these regions for conscious perception in situations where the stimuli are distinct and apparent. Based on these results a model is proposed where sensory regions interact with controlling regions to enable conscious perception. The amount and type of required interaction depend on stimuli and task characteristics, to the extent that higher-order cortical involvement may not be required at all for easily recognizable stimuli.</p>

Although consciousness has been studied since ancient time, how the brain implements consciousness is still considered a great mystery by most. This thesis investigates the neural correlates of consciousness by measuring brain activity with functional magnetic resonance imaging (fMRI) while specific contents of consciousness are defined and maintained in various experimental settings. Study 1 showed that the brain works differently when creating a new conscious percept compared to when maintaining the same percept over time. Specifically, sensory and fronto-parietal regions were activated for both conditions but with different activation patterns within these regions. This distinction between creating and maintaining a conscious percept was further supported by Study 2, which in addition showed that there are both differences and similarities in how the brain works when defining a visual compared to an auditory percept. In particular, frontal cortex was commonly activated while posterior cortical activity was modality specific. Study 3 showed that task difficulty influenced the degree of frontal and parietal cortex involvement, such that fronto-parietal activity decreased as a function of ease of identification. This is interpreted as evidence of the non-necessity of these regions for conscious perception in situations where the stimuli are distinct and apparent. Based on these results a model is proposed where sensory regions interact with controlling regions to enable conscious perception. The amount and type of required interaction depend on stimuli and task characteristics, to the extent that higher-order cortical involvement may not be required at all for easily recognizable stimuli.