Brain activity during the encoding, retention, and retrieval of stimulus representations

Studies of delayed nonmatching-to-sample (DNMS) performance following lesions of the monkey cortex have revealed a critical circuit of brain regions involved in forming memories and retaining and retrieving stimulus representations. Using event-related functional magnetic resonance imaging (fMRI), we measured brain activity in 10 healthy human participants during performance of a trial-unique visual DNMS task using novel barcode stimuli. The event-related design enabled the identification of activity during the different phases of the task (encoding, retention, and retrieval). Several brain regions identified by monkey studies as being important for successful DNMS performance showed selective activity during the different phases, including the mediodorsal thalamic nucleus (encoding), ventrolateral prefrontal cortex (retention), and perirhinal cortex (retrieval). Regions showing sustained activity within trials included the ventromedial and dorsal prefrontal cortices and occipital cortex. The present study shows the utility of investigating performance on tasks derived from animal models to assist in the identification of brain regions involved in human recognition memory.

The semantic interference effect in the picture-word paradigm: An event-related fMRI study employing overt responses

We used event-related functional magnetic resonance imaging (fMRI) to investigate neural responses associated with the semantic interference (SI) effect in the picture-word task. Independent stage models of word production assume that the locus of the SI effect is at the conceptual processing level (Levelt et al. [1999]: Behav Brain Sci 22:1-75), whereas interactive models postulate that it occurs at phonological retrieval (Starreveld and La Heij [1996]: J Exp Psychol Learn Mem Cogn 22:896-918). In both types of model resolution of the SI effect occurs as a result of competitive, spreading activation without the involvement of inhibitory links. These assumptions were tested by randomly presenting participants with trials from semantically-related and lexical control distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt vocalization of picture names occurred in the absence of scanner noise, allowing reaction time (RT) data to be collected. Analysis of the RT data confirmed the SI effect. Regions showing differential hemodynamic responses during the SI effect included the left mid section of the middle temporal gyrus, left posterior superior temporal gyrus, left anterior cingulate cortex, and bilateral orbitomedial prefrontal cortex. Additional responses were observed in the frontal eye fields, left inferior parietal lobule, and right anterior temporal and occipital cortex. The results are interpreted as indirectly supporting interactive models that allow spreading activation between both conceptual processing and phonological retrieval levels of word production. In addition, the data confirm that selective attention/response suppression has a role in resolving the SI effect similar to the way in which Stroop interference is resolved. We conclude that neuroimaging studies can provide information about the neuroanatomical organization of the lexical system that may prove useful for constraining theoretical models of word production. (C) 2001 Wiley-Liss, Inc.

Orthographic/phonological facilitation of naming responses in the picture-word task: An event-related fMRI study using overt vocal responding

In the picture-word interference task, naming responses are facilitated when a distractor word is orthographically and phonologically related to the depicted object as compared to an unrelated word. We used event-related functional magnetic resonance imaging (fMRI) to investigate the cerebral hemodynamic responses associated with this priming effect. Serial (or independent-stage) and interactive models of word production that explicitly account for picture-word interference effects assume that the locus of the effect is at the level of retrieving phonological codes, a role attributed recently to the left posterior superior temporal cortex (Wernicke's area). This assumption was tested by randomly presenting participants with trials from orthographically related and unrelated distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt naming responses occurred in the absence of scanner noise, allowing reaction time data to be recorded. Analysis of this data confirmed the priming effect. Analysis of the fMRI data revealed blood oxygen level-dependent signal decreases in Wernicke's area and the right anterior temporal cortex, whereas signal increases were observed in the anterior cingulate, the right orbitomedial prefrontal, somatosensory, and inferior parietal cortices, and the occipital lobe. The results are interpreted as supporting the locus for the facilitation effect as assumed by both classes of theoretical model of word production. In addition, our results raise the possibilities that, counterintuitively, picture-word interference might be increased by the presentation of orthographically related distractors, due to competition introduced by activation of phonologically related word forms, and that this competition requires inhibitory processes to be resolved. The priming effect is therefore viewed as being sufficient to offset the increased interference. We conclude that information from functional imaging studies might be useful for constraining theoretical models of word production. (C) 2002 Elsevier Science (USA).

Ressonância magnética funcional: mapeamento do córtex motor através da técnica BOLD

A ressonância magnética funcional (RMf) é hoje uma ferramenta fundamental na investigação funcional do cérebro humano, quer em indivíduos saudáveis quer em pacientes com patologias diversas. É uma técnica complexa que necessita de uma aplicação cuidada e rigorosa, e uma compreensão dos mecanismos biofísicos a ela subjacentes, de modo a serem obtidos resultados fiáveis e com melhor aceitação clínica. O efeito BOLD (Blood Oxygenation Level Dependent) é o método mais utilizado para medir e estudar a actividade cerebral e baseia-se nas alterações das propriedades magnéticas da molécula hemoglobina. Com este Projecto propomo-nos optimizar um protocolo de RMf realizada com o efeito BOLD, em voluntários saudáveis, de modo a que este possa ser aplicado em futuros estudos de pacientes com patologias. ABSTRACT - Nowadays functional magnetic resonance imaging (fMRI) is a fundamental tool for the research of human brain function of healthy subjects or patients with several pathologies. It is a complex technique that requires a careful and rigorous application, and an understanding of its biophysical mechanisms, so that reliable results can be obtained with better clinical acceptance. The BOLD effect (Blood Oxygenation Level Dependent) is the most widely used method to measure and study the brain activity and its based on changes in magnetic properties of the hemoglobin molecule. The aim of this project was to optimize a BOLD fMRI protocol on healthy subjects, so it can be applied in future studies of patients with pathologies.

Ressonância magnética funcional: mapeamento do córtex motor através do efeito BOLD

Introdução – A ressonância magnética funcional (RMf) é hoje uma ferramenta fundamental na investigação funcional do cérebro humano, quer em indivíduos saudáveis quer em doentes com patologias diversas. É uma técnica complexa que necessita de uma aplicação cuidada e rigorosa e uma compreensão dos mecanismos biofísicos, de modo a serem obtidos resultados fiáveis e com melhor aceitação clínica. O efeito BOLD (Blood Oxygenation Level Dependent), que se baseia nas propriedades magnéticas da hemoglobina, é o método mais utilizado para medir a atividade cerebral por RMf. Objetivos – Otimizar um protocolo de RMf por efeito BOLD em voluntários saudáveis para mapeamento do córtex motor, de modo a que possa ser aplicado no futuro em doentes com patologias diversas. Metodologia – Foram estudados 34 voluntários saudáveis divididos em 2 grupos de estudo: BOLD 1 e BOLD 2. Com vista à otimização, foram testados no subgrupo BOLD 1 diferentes paradigmas e no subgrupo BOLD 2 foi estudada a influência do tempo de eco (TE). Para as várias condições foram comparados os volumes da região ativada e os níveis de ativação obtidos. Resultados/Discussão – O córtex motor foi identificado em todos os voluntários estudados. Não foram detetadas diferenças estatisticamente significativas quando comparados os resultados obtidos com os diferentes parâmetros de aquisição. Conclusão – O protocolo foi otimizado tendo em conta o nível de conforto reportado pelos voluntários. Uma vez que se pretende aplicar este mesmo protocolo no estudo de doentes, este fator torna-se particularmente relevante.

Ressonância magnética funcional na localização de paradigma motor

Objetivos – Um dos principais objetivos da neurociência tem sido, desde sempre, compreender as funcionalidades do cérebro. A introdução da ressonância magnética funcional contribuiu em grande escala para o desenvolvimento do estudo cerebral. Assim, esta investigação tem como principal objetivo identificar e desenhar os diferentes perfis de localizações cerebrais, a nível do córtex motor, numa população jovem saudável, permitindo, assim, um maior conhecimento nesta área e dando um contributo à área da neurologia. Material e métodos – Foi realizado um estudo de ressonância magnética funcional em 30 indivíduos saudáveis numa clínica de imagiologia médica. Para tal recorreu-se a equipamento adequado para a recolha de dados. O paradigma motor utilizado foi o movimento dos dedos das mãos. Através das imagens obtidas foi medida a área de cada região ativa. Com o suporte do programa SPSS (versão 19) todos os valores foram tratados estatisticamente. Conclusão – Após todo este processo concluiu-se que a área do cérebro maioritariamente ativa, no momento do paradigma motor, encontra-se no hemisfério esquerdo.

Mapeamento das regiões cerebrais associadas ao engano

Mestrado em Radiações aplicadas às Tecnologias da Saúde - Ramo de Ressonância Magnética

Avaliação por fMRI do córtex visual, motor e auditivo através de estimulação sensoriomotora e sonora em desportistas invisuais e desportistas sem deficiência visual

Mestrado em Radiações Aplicadas às Tecnologias da Saúde - Ramo de especialização: Imagem por Ressonância Magnética

Effects of emotional valence and three-dimensionality of visual stimuli on brain activation: an fMRI study

BACKGROUND: Examining changes in brain activation linked with emotion-inducing stimuli is essential to the study of emotions. Due to the ecological potential of techniques such as virtual reality (VR), inspection of whether brain activation in response to emotional stimuli can be modulated by the three-dimensional (3D) properties of the images is important. OBJECTIVE: The current study sought to test whether the activation of brain areas involved in the emotional processing of scenarios of different valences can be modulated by 3D. Therefore, the focus was made on the interaction effect between emotion-inducing stimuli of different emotional valences (pleasant, unpleasant and neutral valences) and visualization types (2D, 3D). However, main effects were also analyzed.METHODS: The effect of emotional valence and visualization types and their interaction were analyzed through a 3x2 repeated measures ANOVA. Post-hoc t-tests were performed under a ROI-analysis approach. RESULTS: The results show increased brain activation for the 3D affective-inducing stimuli in comparison with the same stimuli in 2D scenarios, mostly in cortical and subcortical regions that are related to emotional processing, in addition to visual processing regions. CONCLUSIONS: This study has the potential of clarify brain mechanisms involved in the processing of emotional stimuli (scenarios’ valence) and their interaction with three-dimensionality.

Amygdala activation in response to 2D and 3D emotion-inducing stimuli

Studying changes in brain activation according to the valence of emotion-inducing stimuli is essential in the research on emotions. Due to the ecological potential of virtual reality, it is also important to examine whether brain activation in response to emotional stimuli can be modulated by the three-dimensional (3D) properties of the images. This study uses functional Magnetic Resonance Imaging to compare differences between 3D and standard (2D) visual stimuli in the activation of emotion-related brain areas. The stimuli were organized in three virtual-reality scenarios, each with a different emotional valence (pleasant, unpleasant and neutral). The scenarios were presented in a pseudo-randomized order in the two visualization modes to twelve healthy males. Data were analyzed through a GLM-based fixed effects procedure. Unpleasant and neutral stimuli activated the right amygdala more strongly when presented in 3D than in 2D. These results suggest that 3D stimuli, when used as “building blocks” for virtual environments, can induce increased emotional loading, as shown here through neuroimaging.

Study of behavioural and neural bases of visuo-spatial working memory with an fMRI paradigm based on an n-back task

The goal of this study was to propose a new functional magnetic resonance imaging (fMRI) paradigm using a language-free adaptation of a 2-back working memory task to avoid cultural and educational bias. We additionally provide an index of the validity of the proposed paradigm and test whether the experimental task discriminates the behavioural performances of healthy participants from those of individuals with working memory deficits. Ten healthy participants and nine patients presenting working memory (WM) deficits due to acquired brain injury (ABI) performed the developed task. To inspect whether the paradigm activates brain areas typically involved in visual working memory (VWM), brain activation of the healthy participants was assessed with fMRIs. To examine the task's capacity to discriminate behavioural data, performances of the healthy participants in the task were compared with those of ABI patients. Data were analysed with GLM-based random effects procedures and t-tests. We found an increase of the BOLD signal in the specialized areas of VWM. Concerning behavioural performances, healthy participants showed the predicted pattern of more hits, less omissions and a tendency for fewer false alarms, more self-corrected responses, and faster reaction times, when compared with subjects presenting WM impairments. The results suggest that this task activates brain areas involved in VWM and discriminates behavioural performances of clinical and non-clinical groups. It can thus be used as a research methodology for behavioural and neuroimaging studies of VWM in block-design paradigms.

Optimization of fMRI Processing Parameters for Simutaneous Acquisition of EEG/fMRI in Focal Epilepsy

In the context of focal epilepsy, the simultaneous combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) holds a great promise as a technique by which the hemodynamic correlates of interictal spikes detected on scalp EEG can be identified. The fact that traditional EEG recordings have not been able to overcome the difficulty in correlating the ictal clinical symptoms to the onset in particular areas of the lobes, brings the need of mapping with more precision the epileptogenic cortical regions. On the other hand, fMRI suggested localizations more consistent with the ictal clinical manifestations detected. This study was developed in order to improve the knowledge about the way parameters involved in the physical and mathematical data, produced by the EEG/fMRI technique processing, would influence the final results. The evaluation of the accuracy was made by comparing the BOLD results with: the high resolution EEG maps; the malformative lesions detected in the T1 weighted MR images; and the anatomical localizations of the diagnosed symptomatology of each studied patient. The optimization of the set of parameters used, will provide an important contribution to the diagnosis of epileptogenic focuses, in patients included on an epilepsy surgery evaluation program. The results obtained allowed us to conclude that: by associating the BOLD effect with interictal spikes, the epileptogenic areas are mapped to localizations different from those obtained by the EEG maps representing the electrical potential distribution across the scalp (EEG); there is an important and solid bond between the variation of particular parameters (manipulated during the fMRI data processing) and the optimization of the final results, from which smoothing, deleted volumes, HRF (used to convolve with the activation design), and the shape of the Gamma function can be certainly emphasized.

Past/present and future worries: na fMRI study

For the past decade, numerous imaging techniques gave rise to remarka-ble progresses in the understanding of brain’s structure and function. Amongst the wide variety of studies onto the field of neuroscience, neuropsychiatric re-searches with resource to neuroimaging have attracted increasing attention. The present study will focus on the identification of brain areas recruited while normative subjects read sentences related to past/present or future wor-ries. Our main aim was to accurately characterize these brain areas while providing them with a time-stamp that would hopefully help us understand the implications of past/present memories and future envisioning in worrying episodes. With that purpose, functional magnetic resonance imaging data was collected from ten healthy individuals. The obtained data was processed and statistically treated using the General Linear Model and both Fixed and Ran-dom Effects Analysis for group-level results. Thereafter, a Multi-Voxel Pattern Analysis with Searchlight Mapping was performed in order to find patterns of activation that allow differentiation between conditions. The obtained results indicate higher brain activation while reading sen-tences related to past/present worries when compared to future worry or neu-tral sentences. The main areas include frontal cortex, posterior parietal, occipital and temporal areas. Worrying, per se, was characterized by activation of the medial posterior parietal cortex, left posterior occipital lobe and left central temporal lobe. With the searchlight mapping approach we were able to further identify patterns of distinction between conditions, which were located in the parietal, limbic and frontal lobes.

Biological markers in noninvasive brain stimulation trials in major depressive disorder: a systematic review

Objectives: The therapeutic effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation in patients with major depression have shown promising results; however, there is a lack of mechanistic studies using biological markers (BMs) as an outcome. Therefore, our aim was to review noninvasive brain stimulation trials in depression using BMs. Methods: The following databases were used for our systematic review: MEDLINE, Web of Science, Cochrane, and SCIELO. We examined articles published before November 2012 that used TMS and transcranial direct current stimulation as an intervention for depression and had BM as an outcome measure. The search was limited to human studies written in English. Results: Of 1234 potential articles, 52 articles were included. Only studies using TMS were found. Biological markers included immune and endocrine serum markers, neuroimaging techniques, and electrophysiological outcomes. In 12 articles (21.4%), end point BM measurements were not significantly associated with clinical outcomes. All studies reached significant results in the main clinical rating scales. Biological marker outcomes were used as predictors of response, to understand mechanisms of TMS, and as a surrogate of safety. Conclusions: Functional magnetic resonance imaging, single-photon emission computed tomography, positron emission tomography, magnetic resonance spectroscopy, cortical excitability, and brain-derived neurotrophic factor consistently showed positive results. Brain-derived neurotrophic factor was the best predictor of patients’ likeliness to respond. These initial results are promising; however, all studies investigating BMs are small, used heterogeneous samples, and did not take into account confounders such as age, sex, or family history. Based on our findings, we recommend further studies to validate BMs in noninvasive brain stimulation trials in MDD.

Differential activation of the default mode network in jet lagged individuals

Long-term exposure to transmeridian flights has been shown to impact cognitive functioning. Nevertheless, the immediate effects of jet lag in the activation of specific brain networks have not been investigated. We analyzed the impact of short-term jet lag on the activation of the default mode network (DMN). A group of individuals who were on a transmeridian flight and a control group went through a functional magnetic resonance imaging acquisition. Statistical analysis was performed to test for differences in the DMN activation between groups. Participants from the jet lag group presented decreased activation in the anterior nodes of the DMN, specifically in bilateral medial prefrontal and anterior cingulate cortex. No areas of increased activation were observed for the jet lag group. These results may be suggestive of a negative impact of jet lag on important cognitive functions such as introspection, emotional regulation and decision making in a few days after individuals arrive at their destination.