abstract: The recent spotlight on concussion has illuminated deficits in the current standard of care with regard to addressing acute and persistent cognitive signs and symptoms of mild brain injury. This stems, in part, from the diffuse nature of the injury, which tends not to produce focal cognitive or behavioral deficits that are easily identified or tracked. Indeed it has been shown that patients with enduring symptoms have difficulty describing their problems; therefore, there is an urgent need for a sensitive measure of brain activity that corresponds with higher order cognitive processing. The development of a neurophysiological metric that maps to clinical resolution would inform decisions about diagnosis and prognosis, including the need for clinical intervention to address cognitive deficits. The literature suggests the need for assessment of concussion under cognitively demanding tasks. Here, a joint behavioral- high-density electroencephalography (EEG) paradigm was employed. This allows for the examination of cortical activity patterns during speech comprehension at various levels of degradation in a sentence verification task, imposing the need for higher-order cognitive processes. Eight participants with concussion listened to true-false sentences produced with either moderately to highly intelligible noise-vocoders. Behavioral data were simultaneously collected. The analysis of cortical activation patterns included 1) the examination of event-related potentials, including latency and source localization, and 2) measures of frequency spectra and associated power. Individual performance patterns were assessed during acute injury and a return visit several months following injury. Results demonstrate a combination of task-related electrophysiology measures correspond to changes in task performance during the course of recovery. Further, a discriminant function analysis suggests EEG measures are more sensitive than behavioral measures in distinguishing between individuals with concussion and healthy controls at both injury and recovery, suggesting the robustness of neurophysiological measures during a cognitively demanding task to both injury and persisting pathophysiology. / Dissertation/Thesis / Ph.D. Speech and Hearing Science 2014

A Neuroimagem Funcional evoluiu muito nos últimos anos com o aparecimento de técnicas como Positron Emission Tomography ou PET (Tomógrafo por Emissão de Pósitrons) e Functional Magnetic Ressonance Image ou fMRI (Imagem de RessonÂncia Magnética Funcional) [Belliveau et al., 1991]. Elas permitem a observação de atividade no cérebro com uma resolução de alguns milímetros, e devido a natureza do sinal medido, com uma resolução temporal da ordem de 5 segundos [Kim et al., 1997]. Magnetoencefalografia e Eletroencefalografia (M/EEG), por outro lado, possuem uma resoluçao temporal da ordem de milissegundos, já que o sinal é produzido pela movimentação do íons através das membranas celulares [Nunez and Srinivasan, 2006]. Porém a sua resoluçeo espacial é muito baixa jé que tipicamente são problemas mal postos, com muito mais variáveis do que dados. Um equipamento de M/EEG de alta resolução possui da ordem de O(200) canais, que permitem medidas do campo magnético (para o MEG) ou do potencial elétrico (para o EEG) em O(200) posições em torno da cabeça. Para uma escala com resolução de ordem l existem (L /l )3 variáveis, onde L = aprox. 15cm. Neste trabalho procuramos estudar métodos para aumentar a resolução espacial das técnicas de EEG, pois o mapeamento funcional do cérebro humano esta intimamente relacionado à localização da atividade no espaço bem como no tempo [Friston, 2009] (muitas relativo ao momento de um estímulo externo). Todo o trabalho de localização de fontes para EEG pode ser facilmente estendido para MEG. Métodos Bayesianos são o cenário natural para lidar com problemas mal postos [Wipf and Nagarajan, 2009]. Existem, essencialmente, duas direções nas quais os algoritmos Bayesianos podem ser melhoradas, através da construção de uma melhor verossimilhança ou uma distribuição a Priori. Embora reconheçamos que avanços importantes podem ser feitos no direção anterior, aqui nos concentramos na segunda. Neste trabalho nós introduzimos um método multiescala para construir uma melhor distribuição a Priori. Uma idéia similar foi estudada dentro do contexto mais simples de fMRI [Amaral et al., 2004]. Muitos novos problemas aparecem ao lidar com o caráter vetorial do EEG. O mais importante, é a construção de um conjunto de superfícies renormalizadas que aproximam a região cortical onde a fonte de atividade esta localizada e o problema relacionado de de nir as variáveis relevantes para representar o cérebro em uma escala com menor resolução. A validação do novo algoritmo é sempre um problema essencial. Nós apresentamos resultados que sugerem, em dados simulados, que nosso método pode ser uma alternativa válida para os atuais algoritmos, julgando ambos pela taxa de erros na localização de fontes bem como pelo tempo que eles levam para convergir. / Functional Neuroimaging has evolved in the last few decades with the introduction of techniques such as Positron Emission Tomography or PET and Functional Magnetic Ressonance Image or fMRI [Belliveau et al., 1991]. These allow observing brain activity with a resolution of a few millimeters and, due to the nature of the signal, a time resolution of the order of 5 seconds [Kim et al., 1997]. M/EEG, on the other hand, have a millisecond time resolution, since the signal is produced by the transport of ions through cell membranes [Nunez and Srinivasan, 2006]. However their space resolution is much lower since these are typically ill posed problems with many more unknowns than data points. A high resolution M/EEG has of the order of O(200) data channels, which allow measuring the magnetic or electric field at O(200) positions around the head. For a resolution scale of order l there are O(L l )3 variables, where L = 15cm. In this work we aim at studying methods to increase the spatial resolution of EEG techniques, since functional mapping of the human brain is intimately related to the localization of the activity in space as well as in time [Friston, 2009] (often relative to the time of external stimuli). Any advance in the inverse problem of source localization for EEG can rather easily be extended to deal with MEG. Bayesian methods are the natural setting to deal with ill posed problems [Wipf and Nagarajan, 2009]. There are essentially two directions in which Bayesian algorithms can be improved, by building a better likelihood or a prior distribution. While we recognize that important advances can be done in the former direction we here concentrate in the latter. In this work we introduce a multiscale method to build an improved prior distribution. A similar idea has been studied within an easier context of fMRI [Amaral et al., 2004]. Several new problems appear in dealing with the vectorial character of EEG. The most important, is the construction of a set of renormalized lattices that approximate the cortex region where the source activity is located and the related problem of de ning the relevant variables in coarser scale representation of the cortex. Validation of a new algorithm is always an essential problem. We present results which suggest on simulated data, that our method might be a valid alternative to current algorithms, judged both by the rate of errors in source localization as well as by the time it takes to converge.

Com intuito de avaliar o processo cognitivo cerebral e o desempenho de médicos veterinários especializados em radiologia, este estudo proporcionou, através de um sistema computacional, tarefas de questões radiológicas. Os 29 voluntários foram divididos por gênero: homens (n=13) e mulheres (n=16); e por tempo de especialidade: iniciantes (n=13), experientes (n=8) e seniores (n=8). Quatorze casos foram selecionados com diferentes níveis de dificuldade a partir de imagens radiográficas de cães e gatos e foram escaneadas e colocadas em um programa chamado Enscer®, adaptado para a realização deste estudo. Os casos eram divididos em três partes, nomeadas, história clínica, imagem radiográfica e decisão diagnóstica. Durante as etapas, foram realizados eletroencefalogramas dos voluntários, que resultaram em mapeamentos cerebrais. Além disso, foi feita avaliação das respostas corretas, incorretas e dos tempos utilizados para as tarefas. Através das avaliações estatísticas dos resultados foi possível concluir que radiologistas veterinários com maior tempo de especialidade foram estatisticamente mais rápidos nas tarefas e tiveram melhor desempenho diagnóstico; voluntários com maior tempo de especialidade ativaram áreas cerebrais diferentes dos menos experientes; o desempenho diagnóstico foi quantitativamente igual em voluntários de ambos os gêneros e o mapeamento cerebral do grupo masculino foi diferente do grupo feminino, mesmo com desempenho igual nas atividades / With intention to evaluate the cerebral cognitive process and the performance of medical veterinarians specialized in radiology, this study provided, through a computerized system, tasks of radiological questions. The 29 volunteers were divided by gender: man (n=13) and woman (n=16); and by time of experience: beginners (n=13), experienced (n=8) and seniors (n=8). Fourteen cases were selected with different levels of difficulty from radiographic images of dogs and cats and had been scanned and processed by a software called Enscer®, adapted for the accomplishment of this study. The cases were divided into three parts, namely, clinical history, radiographic image and diagnostic decision. During the stages the electroencephalography was carried through, which resulted in the cerebral mapping. Moreover, evaluation of the correct and incorrect answers and of the times used for the tasks was made. Through the statistical evaluations of the results it was possible to conclude that radiologists veterinarians with more time of experience had been statistically faster in the tasks and had had better diagnostic performance; volunteers with more time of experience had activated different cerebral areas than volunteer with less experience; the diagnostic performance was quantitatively equal in volunteers of both genders and the cerebral mapping of the masculine group was different of the feminine group, even with equal performance in the activities

A inclusão da eletroencefalografia nos protocolos de pesquisa diagnóstica para DA é plenamente justificada por sua larga disponibilidade, baixo custo, alta sensibilidade, o que possibilita a realização de exames seriados e o acompanhamento da evolução do estudo neurológico. Objetivo: Determinar um índice de corte, para utilizaçào na prática clínica, no auxilio diagnóstico da doença de Alzheimer. Metodologia: Avaliamos dois grupos de indivíduos compostos por 57 voluntários normais e idade superior a 50 anos comparados a 50 indivíduos com DA provável. Realizamos registros de EEG em vigília, olhos fechados e repouso por 30 minutos e computamos as potências espectrais das bandas de frequência alfa e teta, para todos os eletrodos, e calculamos a razão alfa/teta. Realizamos a regressão logística das variáveis razão alfa/teta da potência média do eletrodo C3 e do eletrodo O1e calculamos uma fórmula para o auxílio no diagnóstico da DA com um acerto cuja, sensibilidade para DA de 76, 4 % e especificidadede 84,6 % e a área sob a curva ROC 0.92. Conclusão: A regressão logística da razão alfa/teta do Espectro da potência média do EEG é um bom marcador para discriminar pacientes com doença de Alzheimer de controles normais / The inclusion of electroencephalography in diagnostic research protocols for AD is fully justified given EEG\'s wide availability, low cost and high sensitivity, allowing serial exams and neurological evolution follow-ups. Objective: To determine a screening index for use in routine clinical practice to aid the diagnosis of Alzheimer\'s disease. Methodology: Two groups of individuals older than 50 years, comprising a control group of 57 normal volunteers and a study group of 50 patients with probable AD, were compared. EEG recordings were performed of subjects in a wake state with eyes closed at rest for 30 mins. Spectral potentials of the alpha and theta bands were computed for all electrodes and the alpha/theta ratio calculated. Logistic regression of the variables alpha/theta of the mean potential of the C3 and O1 electrodes was carried out. A formula was calculated to aid the diagnosis of AD yielding 76.4 % sensitivity and 84.6 specificity for AD with an area under the ROC curve of 0.92. Conclusion: Logistic regression of the alpha/theta of the Spectrum of the mean potential of EEG represents a good marker for discriminating between AD patients and normal controls

Orientador: Roberto José Maria Covolan / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-25T18:35:31Z (GMT). No. of bitstreams: 1 Beltramini_GuilhermeCoco_D.pdf: 12819168 bytes, checksum: 3ea327ddb4007610872637f91cf058e4 (MD5) Previous issue date: 2014 / Resumo: Epilepsia é uma doença neurológica que afeta pessoas no mundo todo, atingindo em torno de 1% da população mundial. Aproximadamente 30% dos pacientes não respondem bem ao tratamento com medicamentos. A abordagem cirúrgica é uma alternativa recomendada somente quando se localiza, de forma precisa, a região epileptogênica, razão pela qual os pacientes são submetidos a diversas avaliações invasivas e não-invasivas, incluindo exames de neuroimagem estrutural e funcional. A técnica de EEG-RMf simultâneos surgiu da combinação do EEG, de uso consagrado em pacientes com epilepsia, com a RMf, procedimento cada vez mais aplicado em estudos funcionais do cérebro, tendo sido encarada desde sua concepção inicial com a perspectiva de se constituir em um novo exame não invasivo na avaliação pré-cirúrgica em epilepsia. As dificuldades instrumentais inerentes a esta técnica têm sido superadas mais rapidamente do que o desenvolvimento de métodos empregados na análise e interpretação dos resultados gerados através dela. Isto ocorre em parte devido à complexidade e diversidade de causas da epilepsia, que afeta o cérebro do ponto de vista estrutural e funcional, podendo atingi-lo desde o âmbito genético até níveis macroscópicos. Neste trabalho, estabelecemos uma sequência de procedimentos para a aquisição e análise de dados de EEG-RMf, possibilitando o uso deste exame como uma informação adicional na avaliação pré-cirúrgica. Criamos um programa de computador chamado SAfE (Straightforward Analysis of fMRI and EEG-fMRI), que permite realizar as análises de experimentos de EEG-RMf de forma direta e segura. Após aplicar as correções no sinal do EEG e realizar a marcação da atividade epileptiforme, mapas estatísticos de RMf podem ser obtidos através de uma interface gráfica simples, com pouca intervenção do usuário. Para observar simultaneamente os aspectos temporais e espaciais das alterações hemodinâmicas relacionadas com os diferentes tipos de atividade epileptiforme de cada paciente, foi proposta e incorporada ao SAfE uma forma original de se descrever os resultados. São gerados mapas estatísticos para diferentes posições do pico da função resposta hemodinâmica, que são então analisados sequencialmente, observando-se diferentes parâmetros, tais como o valor de T máximo e número de voxels acima do limiar. A abordagem aqui proposta para a análise dos dados de EEG-RMf sugere que os mapas estatísticos dos pacientes sejam examinados preferencialmente de forma individual, pois parte importante da informação pode ser perdida quando se combinam os resultados em análises de grupo. Os resultados obtidos revelam a alta complexidade dos mecanismos geradores de atividade epileptiforme, pois as redes cerebrais envolvidas mostram um elevado grau de heterogeneidade entre os pacientes e entre os diferentes tipos de atividade epileptiforme considerados. Possivelmente sistemas locais e remotos interagem de forma a causar alterações crônicas que afetam a propagação da crise e da atividade epileptiforme. A técnica de EEG-RMf tem se mostrado uma aplicação com valor clínico promissor, porém requer validação através da comparação com procedimentos mais bem estabelecidos. Embora os benefícios desta técnica sejam limitados em pacientes com atividade epileptiforme de difícil detecção, entende-se que seu desenvolvimento deverá contribuir para tornar mais robusta a avaliação pré-cirúrgica realizada atualmente / Abstract: Epilepsy is a neurological disease that affects people worldwide, reaching about 1% of the world population. Approximately 30% of the patients do not respond well to treatment with medication. The surgical approach is an alternative recommended only when the epileptogenic region can be precisely localized. For this reason patients are subjected to various invasive and non-invasive assessments, including structural and functional neuroimaging exams. Simultaneous EEG-fMRI recordings originated from the combination of EEG, which has traditional use in epilepsy patients, with fMRI, a procedure increasingly applied to functional studies of the brain. This technique has been treated since its conception as a potential new non-invasive exam in the presurgical evaluation in epilepsy. Its inherent instrumental difficulties have been overcome more rapidly than the development of methods employed in the analysis and interpretation of the results. This is partly due to the complexity and diversity of causes of epilepsy, which affects the brain from the structural and functional standpoints, possibly disturbing it from genetic to macroscopic levels. In this work, we established a sequence of procedures for the acquisition and data analysis of EEG-fMRI, enabling the use of this technique as an additional exam in the presurgical evaluation. We created a computer program called SAfE (Straightforward Analysis of fMRI and EEG-fMRI), which allows straightforward and safe EEG-fMRI data analysis. After performing the EEG signal correction and identifying the epileptiform activity, fMRI statistical maps can be obtained through a simple graphical interface with little user input. An original form of describing the results was proposed and integrated in SAfE, in order to simultaneously examine the temporal and spatial aspects of the hemodynamic changes associated with the different types of epileptiform activity of each patient. Statistical maps are generated for different peak positions of the hemodynamic response and are then sequentially analyzed considering different parameters such as the maximum T value and the number of voxels above threshold. The approach proposed here for the EEG-fMRI data analysis suggests that the statistical maps of the patients should preferably be examined individually, because important information can be lost when the results are combined in group analyses. The obtained results reveal the high complexity of the mechanisms that generate epileptiform activity, because the brain networks involved show an elevated degree of heterogeneity among patients and among the different types of epileptiform activity. Possibly local and remote systems interact in such a way to cause chronic changes that affect the spread of the seizure and epileptiform activity. The EEG-fMRI technique has shown to be an application with promising clinical value, but requires validation via comparison with more established procedures. Although the benefits of this technique are limited in patients whose epileptiform activity is difficult to detect, its development is expected to make the current presurgical evaluation more robust / Doutorado / Física / Doutor em Ciências

Doctorat en Sciences de la motricité / info:eu-repo/semantics/nonPublished

For many, the course of major depressive disorder (MDD) is recurrent, with periods of remission between major depressive episodes (MDEs); those in remission are known to be at elevated risk of future MDEs. A common and distressing symptom of MDD is overgeneralised self-blame, and this also persists into remission. In order to study the involvement of self-blame in vulnerability to MDD, a large cohort of participants was recruited: a group with remitted MDD (rMDD) and a matched healthy control (HC) group with no personal or family history of MDD. Participants completed electrophysiological and neuropsychological tasks. The rMDD group also completed a 14-month follow-up period, during which symptoms were monitored at intervals; this was to study the predictive effects of electrophysiological and neuropsychological variables, with a view to development of a biomarker with predictive value. The main method was electroencephalography (EEG), chosen for its high temporal resolution in comparison to a commonly used technique, functional magnetic resonance imaging (fMRI). On a practical level, EEG is also more cost effective and widely available, making it more suitable for future clinical transfer of any biomarker developed. A task previously used in fMRI was adapted for EEG; in this task, short sentences designed to evoke negative feelings related to the self and others were presented. The theta signal was abnormally sustained over time during self-blame in the rMDD group relative to the HC group. Given the involvement of theta in temporal binding, this may represent a correlate of dysfunction within the neural network underpinning self-blaming emotions. Correlation of sustained theta with separately collected fMRI data indicated the dorsolateral prefrontal cortex (dlPFC) was involved in this network. In a source analysis of the EEG data, the dlPFC was identified again; it showed reduced activation in the rMDD group relative to the HC group during other-blame. In summary, activation of the dlPFC appears to be adaptive in both self- and other-blame, as the HC group showed higher activation than the rMDD group; further work is required to confirm the clinical relevance of this. For a separate study of memory overgeneralisation, a known feature of MDD, a novel associative memory task was designed. A loss of bias towards remembering positive memories was found in a subgroup of the rMDD cohort with early life stress (ELS). This reduced positive bias correlated with the number of past MDEs, indicating that the cumulative effect of MDEs reactivating early traumatic memories leads to selective loss of positive memory bias. In summary, although no electrophysiological or neurocognitive predictive markers of recurrence risk were found, clear effects were seen in the cross-sectional results. Importantly, EEG was also validated as a technique for detecting self-blame-selective neural correlates of depression vulnerability. There were clear effects in the temporal domain, which highlight the benefits of EEG above other imaging techniques. However, the sources identified did not correlate with parallel fMRI work, so further work is required to understand the temporal dynamics of these sources. This research provides a platform from which future EEG investigations can develop.

Traumatic brain injuries (TBI) are one of the leading causes of disability worldwide (Zitnay, 2008), yet one of the least understood neurological conditions (Duncan, 2005). Research has examined short-term deficits; however, less focus has been on the consequences of multiple concussions. Previous electroencephalography (EEG) concussion research has examined the N200 and P300 human event-related potential (ERP) components, yielding inconclusive results (Duncan, Kosmidis & Mirsky, 2005). An ERP component not as frequently examined is the reward positivity, generated by the anterior cingulate cortex (ACC), a region which experiences increased anatomical stress following injury. In this study, 51 students from the University of Victoria took a ‘Concussion Survey’ to determine participant history and groups; no history of concussion, a single injury or multiple injuries (2+). Participants performed an oddball and decision-making task while EEG data was collected. No significant differences were found between groups for the N200, P300 or reward positivity peak latencies or amplitudes. Both concussion groups yielded attenuated peak amplitudes, but no differences existed between the group with a single concussion versus multiple. Unexpectedly, N200 and reward positivity peak latencies were greater in the group with single injuries, compared to those with a history of multiple concussions. This study adds to a continuous line of inconclusive research on the N200 and P300, suggesting minimal cognitive deficits result from concussive injuries. Furthermore, no noticeable differences were observed between groups with a single versus multiple injuries. While the ACC is located in a region of increased stress following TBI, functional deficits impacting the reward positivity may not be as significant as previously hypothesized. Results may be impacted by confounding variables, including not reliably being able to account for time since injury, injury severity and differences in gender dispersion of participants. With concussions on the rise, continued research, particularly longitudinally and within-subjects is critical for the advancement of both TBI prevention and management. / Graduate

According to the predictive coding approach to perception, the brain uses predictions based on previous experience to optimise perception, by allocating more computational resources to important or unexpected stimuli. Overall, predictions allow faster and more accurate recognition, but occasionally, when the prediction is incorrect, it may lead to a misperception. The aim of this thesis was to investigate the influence of top - down processes on perceptual decisions. I utilised misperceptions as a signature of those top - down influences and Signal Detection Theory to assess their size, type and direction. I used Electroencephalography to determine the stage of information processing at which different types of predictions influence sensory processing.The empirical studies are clustered around Topic 1: Influence of Predictions on Perception, Topic 2: Types of Predictions and Topic 3: Value as Modulator of Perception.Studies clustered in Topic 1 analysed and quantified the influence of predictions on perceptual decisions and showed that misperceptions can be triggered by wrong predictions only in very specific circumstances. In particular, misperceptions occurred only if there was some degree of correspondence between the wrong prediction and the sensory input. Otherwise, predictions were easily rejected, increasing the overall accuracy. I also demonstrated that misperceptions were most likely to happen in a window on the continuum of input quality where the stimulus - related uncertainty was highest. Topic 2 comprised experiments investigating different types of predictions and their interaction. Behavioural (but not EEG) results revealed interference between passive and active expectations. The early event related (ERP) components N1 and P2, as well as the P300, were all modulated by expectations. Expected events either increased or decreased the P300 amplitude, depending on whether the expected item was predictable and thus ignored, or awaited and thus flagged for further processing. This suggests that P300 might be an index of top - down resource allocation. Experiments within Topic 3 studied the influence of values, as examples of executive processes, on perceptual decisions, using either natural or acquired high - value stimuli. The results suggested that the process of recognition is adjusted in a top - down manner to account for the cost and benefit values related to different outcomes. The trade - off between processing time and accuracy is not fixed, but can be adjusted to optimise recognition in the task at hand. Furthermore, value can change the focus of perception, resulting in different elements of the sensory input being amplified or ignored. Overall, these results showed that misperceptions are 'intelligent mistakes' - a by - product of a top-down, prediction - based optimisation strategy that decreases the computational load, while increasing accuracy and improving the allocation of computational resources.

An important clinical research question to be answered in the field of neurofeedback (NF) is whether amplitude training affects connectivity between cortical sites. This study hypothesizes that, following NF amplitude training, there will be a difference in QEEG coherence and phase measures between NF training done using referential montages and using sequential montages. The study examined case files of 16 adult clients from the University of North Texas Neurotherapy Lab who had received NF training that consisted of either referential or sequential placement amplitude training (no coherence training) and who received both pre- and post- treatment QEEGs. Sixty-eight percent of the cases consisted of referential placements, while 34% of the cases consisted of sequential placements. All frontal site phase and coherence abnormal z-scores at pre-treatment were converted to deviation scores and compared by general linear model analysis of variance to post-treatment deviation scores. Effect size r-values and eta square values indicate that differences between referential and sequential electrode placements after NF amplitude training are moderately high. This study shows that referential placements tend to increase phase scores and decrease coherence scores, while sequential placements tend to decrease phase scores and increase coherence scores.