Étude électrophysiologique de la suppression interoculaire : implication pour l'amblyopie

L’amblyopie est un trouble développemental de la vision binoculaire. Elle est typiquement caractérisée par des atteintes de l’acuité visuelle et de la stéréoscopie. Toutefois, de plus en plus d’études indiquent la présence d’atteintes plus étendues telles que les difficultés d’attention visuelle ou de lecture. L’amblyopie est généralement expliquée par une suppression interoculaire au niveau cortical, considérée comme chronique ou permanente à l’extérieur de la période développementale. Or, un nombre croissant d’études suggèrent que des interactions binoculaires normales seraient présentes chez les amblyopes adultes. Dans une première étude, nous avons tenté d’identifier un marqueur électrophysiologique de la vision binoculaire. Nous avons enregistré des potentiels évoqués visuels chez des observateurs normaux à qui l’on a induit une dysfonction binoculaire. Les interactions binoculaires étaient caractérisées à l’aide de patrons (facilitation, moyennage et suppression) en comparant les réponses monoculaires et binoculaires. De plus, ces interactions étaient quantifiées à partir d’index d’intégration continus en soustrayant la somme des réponses monoculaires de la réponse binoculaire. Les résultats indiquaient que les patrons d’interaction n’étaient pas optimaux pour estimer les performances stéréoscopiques. Ces dernières étaient, en revanche, mieux expliquées par notre index d’intégration binoculaire. Ainsi, cette étude suggère que l’électrophysiologie est un bon prédicteur de la vision binoculaire. Dans une deuxième étude, nous avons examiné les corrélats neuronaux et comportementaux de la suppression interoculaire chez des amblyopes adultes et des observateurs normaux. Des potentiels évoqués visuels stationnaires ont été enregistrés en utilisant un paradigme de suppression par flash. La suppression était modulée par un changement de contraste du stimulus flash (10, 20, 30, ou 100%), ou le suppresseur, qui était présenté soit dans l’œil dominant ou non-dominant (ou amblyope). Sur le plan comportemental, la suppression interoculaire était observée indépendamment de l’œil stimulé par le flash chez les contrôles. Au contraire, chez les amblyopes, la suppression était asymétrique (c’est-à-dire supérieure lorsqu’elle provenait de l’œil dominant), ce qui suggérait une suppression chronique. De manière intéressante, l’œil amblyope a supprimé l’œil dominant à haut niveau de contraste. Sur le plan électrophysiologique, l’effet de suppression interoculaire observé à la région occipitale était équivalent dans chaque groupe. Toutefois, les réponses électrophysiologiques à la région frontale chez les amblyopes n’étaient pas modulées comme celles des contrôles; la suppression de l’œil amblyope était manifeste même à bas contraste. Nous résultats supportent ainsi l’existence d’interaction binoculaire fonctionnelle chez les amblyopes adultes ainsi que l’implication d’un réseau cortical étendu dans la suppression interoculaire. En somme, l’amblyopie est une condition complexe dont les atteintes corticales et les déficits fonctionnels semblent globaux. L’amblyopie ne doit plus être considérée comme limitée à une dysfonction de l’aire visuelle primaire. La suppression interoculaire semble un point central de cette problématique, mais encore beaucoup d’études seront nécessaires afin de déterminer l’ensemble des mécanismes impliqués dans celle-ci.

Changements corticaux et sous-corticaux des événements du sommeil lent au cours du vieillissement

Les avancées techniques et méthodologiques de la neuroscience ont permis de caractériser le sommeil comme un état actif et dynamique où des événements neuronaux cohésifs organisent les fonctions cérébrales. Les fuseaux de sommeil et les ondes lentes sont les marqueurs électroencéphalographiques de ces événements, et la mesure de leurs paramètres reflète et nuance les interactions neuronales à l’oeuvre pendant le sommeil lent. Considérant leur implication dans les fonctions hypniques et cognitives, les événements du sommeil lent sont particulièrement pertinents à l’étude du vieillissement, où l’intégrité de ces fonctions est mise au défi. Le vieillissement normal s’accompagne non seulement de réductions importantes des paramètres composant les événements du sommeil lent, mais aussi de modifications précises de l’intégrité anatomique et fonctionnelle du cerveau. Récemment, les études ont souligné la régulation locale des événements du sommeil lent, dont l’évolution avec l’âge demeure toutefois peu explorée. Le présent ouvrage se propose de documenter les liens unissant la neurophysiologie du sommeil, le vieillissement normal et l’activité régionale du cerveau par l’évaluation topographique et hémodynamique des événements du sommeil lent au cours du vieillissement. Dans une première étude, la densité, la durée, l’amplitude et la fréquence des fuseaux de sommeil ont été évaluées chez trois groupes d’âge au moyen de l’analyse topographique et paramétrique de l’électroencéphalogramme. Dans une seconde étude, les variations hémodynamiques associées à l’occurrence et modulées par l’amplitude des ondes lentes ont été évaluées chez deux groupes d’âge au moyen de l’électroencéphalographie combinée à l’imagerie par résonance magnétique fonctionnelle. Globalement, les résultats obtenus ont indiqué : 1) une dichotomie des aires corticales antérieures et postérieures quant aux effets d’âge sur les paramètres des fuseaux de sommeil; 2) des variations de la réponse hémodynamique associées aux ondes lentes dans une diversité de régions corticales et sous-corticales chez les personnes âgées. Ces résultats suggèrent la réorganisation fonctionnelle de l’activité neuronale en sommeil lent à travers l’âge adulte, soulignent l’utilité et la sensibilité des événements du sommeil lent comme marqueurs de vieillissement cérébral, et encouragent la recherche sur l’évolution des mécanismes de plasticité synaptique, de récupération cellulaire et de consolidation du sommeil avec l’âge.

Evaluación de la conectividad cerebral bajo fármacos mediante análisis no lineal del EEG

Màster Oficial en Enginyeria Biomèdica

¿Tenemos libre albedrío? Objeciones empíricas y filosóficas a Benjamin Libet.

Benjamin Libet ha argumentado que cambios específicos en la actividad electroencefalográfica del córtex cerebral son registrados varios cientos de milisegundos antes que las personas tengan la intención consciente para actuar. Según Libet este hallazgo prueba que los movimientos voluntarios se inician de manera inconsciente. Siendo así, pone en duda nuestra percepción de libre albedrío según la cual nosotros somos iniciadores conscientes de nuestras acciones voluntarias. En este artículo haré objeciones empíricas a su modelo experimental argumentando que Libet no mide en realidad lo que él cree que está midiendo y, que el uso de electroencefalografía con electrodo de registro en cuero cabelludo no suministra datos fiables que permitan correlacionar cambios de la actividad cerebral y fenómenos psíquicos. También haré objeciones teóricas a las conclusiones filosóficas derivadas de sus experimentos, argumentado que la acción simple (mover el dedo) no puede ser una acción paradigmática para estudiar libre albedrío y que Libet al no estudiar la naturaleza de las intenciones distales ni su probable rol causal en la formación de intenciones proximales, no puede demostrar que el cerebro decide inconscientemente iniciar la acción. Concluyo que Libet nunca llega a probar que no actuamos por nuestro propio libre albedrío.

Does high-frequency repetitive transcranial magnetic stimulation produce residual and/or cumulative effects within an experimental session?

A common procedure for studying the effects on cognition of repetitive transcranial magnetic stimulation (rTMS) is to deliver rTMS concurrent with task performance, and to compare task performance on these trials versus on trials without rTMS. Recent evidence that TMS can have effects on neural activity that persist longer than the experimental session itself, however, raise questions about the assumption of the transient nature of rTMS that underlies many concurrent (or "online") rTMS designs. To our knowledge, there have been no studies in the cognitive domain examining whether the application of brief trains of rTMS during specific epochs of a complex task may have effects that spill over into subsequent task epochs, and perhaps into subsequent trials. We looked for possible immediate spill-over and longer-term cumulative effects of rTMS in data from two studies of visual short-term delayed recognition. In 54 subjects, 10-Hz rTMS trains were applied to five different brain regions during the 3-s delay period of a spatial task, and in a second group of 15 subjects, electroencephalography (EEG) was recorded while 10-Hz rTMS was applied to two brain areas during the 3-s delay period of both spatial and object tasks. No evidence for immediate effects was found in the comparison of the memory probe-evoked response on trials that were vs. were not preceded by delay-period rTMS. No evidence for cumulative effects was found in analyses of behavioral performance, and of EEG signal, as a function of task block. The implications of these findings, and their relation to the broader literature on acute vs. long-lasting effects of rTMS, are considered.

Modulation of visually evoked cortical fMRI responses by phase of ongoing occipital alpha oscillations

Using simultaneous electroencephalography as a measure of ongoing activity and functional magnetic resonance imaging (fMRI) as a measure of the stimulus-driven neural response, we examined whether the amplitude and phase of occipital alpha oscillations at the onset of a brief visual stimulus affects the amplitude of the visually evoked fMRI response. When accounting for intrinsic coupling of alpha amplitude and occipital fMRI signal by modeling and subtracting pseudo-trials, no significant effect of prestimulus alpha amplitude on the evoked fMRI response could be demonstrated. Regarding the effect of alpha phase, we found that stimuli arriving at the peak of the alpha cycle yielded a lower blood oxygenation level-dependent (BOLD) fMRI response in early visual cortex (V1/V2) than stimuli presented at the trough of the cycle. Our results therefore show that phase of occipital alpha oscillations impacts the overall strength of a visually evoked response, as indexed by the BOLD signal. This observation complements existing evidence that alpha oscillations reflect periodic variations in cortical excitability and suggests that the phase of oscillations in postsynaptic potentials can serve as a mechanism of gain control for incoming neural activity. Finally, our findings provide a putative neural basis for observations of alpha phase dependence of visual perceptual performance.

Balanced excitation and inhibition: Model based analysis of local field potentials

We have developed a model of the local field potential (LFP) based on the conservation of charge, the independence principle of ionic flows and the classical Hodgkin–Huxley (HH) type intracellular model of synaptic activity. Insights were gained through the simulation of the HH intracellular model on the nonlinear relationship between the balance of synaptic conductances and that of post-synaptic currents. The latter is dependent not only on the former, but also on the temporal lag between the excitatory and inhibitory conductances, as well as the strength of the afferent signal. The proposed LFP model provides a method for decomposing the LFP recordings near the soma of layer IV pyramidal neurons in the barrel cortex of anaesthetised rats into two highly correlated components with opposite polarity. The temporal dynamics and the proportional balance of the two components are comparable to the excitatory and inhibitory post-synaptic currents computed from the HH model. This suggests that the two components of the LFP reflect the underlying excitatory and inhibitory post-synaptic currents of the local neural population. We further used the model to decompose a sequence of evoked LFP responses under repetitive electrical stimulation (5 Hz) of the whisker pad. We found that as neural responses adapted, the excitatory and inhibitory components also adapted proportionately, while the temporal lag between the onsets of the two components increased during frequency adaptation. Our results demonstrated that the balance between neural excitation and inhibition can be investigated using extracellular recordings. Extension of the model to incorporate multiple compartments should allow more quantitative interpretations of surface Electroencephalography (EEG) recordings into components reflecting the excitatory, inhibitory and passive ionic current flows generated by local neural populations.

Issues and benefits of using 3D Interfaces: visual and verbal tasks

Spatial memory is important for locating objects in hierarchical data structures, such as desktop folders. There are, however, some contradictions in literature concerning the effectiveness of 3D user interfaces when compared to their 2D counterparts. This paper uses a task-based approach in order to investigate the effectiveness of adding a third dimension to specific user tasks, i.e. the impact of depth on navigation in a 3D file manager. Results highlight issues and benefits of using 3D interfaces for visual and verbal tasks, and introduces the possible existence of a correlation between aptitude scores achieved on the Guilford- Zimmerman Orientation Survey and Electroencephalography- measured brainwave activity as participants search for targets of variable perceptual salience in 2D and 3D environments.

Movement intention detection from autocorrelation of EEG for BCI

Movement intention detection is important for development of intuitive movement based Brain Computer Interfaces (BCI). Various complex oscillatory processes are involved in producing voluntary movement intention. In this paper, temporal dynamics of electroencephalography (EEG) associated with movement intention and execution were studied using autocorrelation. It was observed that the trend of decay of autocorrelation of EEG changes before and during the voluntary movement. A novel feature for movement intention detection was developed based on relaxation time of autocorrelation obtained by fitting exponential decay curve to the autocorrelation. This new single trial feature was used to classify voluntary finger tapping trials from resting state trials with peak accuracy of 76.7%. The performance of autocorrelation analysis was compared with Motor-Related Cortical Potentials (MRCP).

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

Processing of hierarchical syntactic strusture in music

Hierarchical structure with nested nonlocal dependencies is a key feature of human language and can be identified theoretically in most pieces of tonal music. However, previous studies have argued against the perception of such structures in music. Here, we show processing of nonlocal dependencies in music. We presented chorales by J. S. Bach and modified versions inwhich the hierarchical structure was rendered irregular whereas the local structure was kept intact. Brain electric responses differed between regular and irregular hierarchical structures, in both musicians and nonmusicians. This finding indicates that, when listening to music, humans apply cognitive processes that are capable of dealing with longdistance dependencies resulting from hierarchically organized syntactic structures. Our results reveal that a brain mechanism fundamental for syntactic processing is engaged during the perception of music, indicating that processing of hierarchical structure with nested nonlocal dependencies is not just a key component of human language, but a multidomain capacity of human cognition.

Realidade virtual na atividade cerebral: um estudo comparativo entre estados emocionais de adultos jovens e idosos

The association of Virtual Reality (VR) to clinical practice has become common in the recent years, showing to be an additional tool on health care, especially for elderly. Its use has been related to higher therapeutic adhesion levels and well being sensation. Such emotional based aspects are often observed by subjective tools of relative validity. This study analyzed the immediate effects of varied VR contexts balance training over emotional behavior, which was observed under peaks of maximum expression of EEG waves. Methodology: 40 individuals, divided in two groups, both gender, 20 young and 20 elderly, were submitted to a 60 minutes intervention, including balance training under VR. The first 25 minutes referred to initial evaluation, general orientation and cognitive assessment by the use of Mini Mental. The next ten minutes were designated to the avatar creation and tutorial video presentation. Through the following 20 minutes, the individuals from both groups were exposed to the exact same sequence of games under virtual contexts, while submitted to electroencephalography by Emotiv EPOC® focusing Adhesion, Frustration and Meditation states. The virtual interface was provided by the Nintendo® game, Wii Fit Plus, with the scenarios Balance Bubble (1), Penguin (2), Soccer (3), Tight Rope (4) and Table Tilt (5). Finally, a questionnaire of personal impressions was applied on the 5 minutes left. Results: data collected showed 64,7% of individuals from both groups presented higher concentration of adhesion peaks on Balance Bubble game. Both groups also presented similar behavior regarding meditation state, with marks close to 40%, each, on the same game, Table Tilt. There was divergence related to the frustration state, being the maximum concentration for the young group on the Soccer game (29,3%), whilst the elderly group referred highest marks to Tight Rope game (35,2%). Conclusion: Findings suggest virtual contexts can be favorable to adhesion and meditation emotional patterns induction, regardless age and for both sexes, whilst frustration seems to be more related to cognitive motor affordance, likely to be influenced by age. This information is relevant and contributes to the orientation for the best choice of games applied in clinical practice, as for other studies regarding this topic

Correlato eletroencefalográfico do estado vibracional

O estado vibracional (EV) é descrito como uma sensação de vibração intensa por todo o corpo, em que o sujeito se mantém num estado de relaxamento psicofisiológico que pode ser gerado de forma espontânea ou autoinduzida. Pessoas que aplicam esta técnica relatam alterações do estado mental e emocional, tais como: relaxamento, disposição, limpidez de pensamento, equilíbrio emocional, melhoria do raciocínio, bemestar, entre outros. Estas são, entretanto observações subjetivas, sendo a mensuração deste fenômeno uma lacuna e um desafio para a ciência. O objetivo desta pesquisa é explorar sistematicamente o estado vibracional no âmbito da neurociência. Desta forma, medidas eletroencefalográficas (EEG) foram utilizadas para observar se a sensação subjetiva de EV é acompanhada por mudanças na atividade elétrica cerebral. Além disso, para avaliar se o EV provoca algum efeito positivo em funções cognitivas como atenção e memória, foi utilizado um teste de reconhecimento de palavras antes e depois da aplicação da técnica de EV. Foram também aplicados questionários de dados gerais socioeconômicos e de saúde, do perfil de estados de humor, de qualidade do sono, além de inventários psicológicos. O foco inicial do trabalho foi a análise estatística dos dados de EEG, ficando as outras análises para uma etapa posterior. Dois grupos de voluntários foram analisados, o primeiro formado por 14 sujeitos que praticam a técnica de EV há pelo menos 10 anos (Grupo Experiente - GEXP), e o segundo formado por 11 sujeitos que nunca haviam realizado a técnica (Grupo Controle - GCONT). O GCONT obteve instruções sobre a técnica de EV antes dos experimentos. Foram realizadas análises estatísticas dos registros eletroencefalográficos, para comparar os grupos, em quatro condições: Basal, Relaxamento, Não-EV (período em que o sujeito está engajado na tarefa, mas ainda não percebe o EV) e EV (período em que o sujeito percebe o EV). Uma vez que os sujeitos do GCONT relataram não ter conseguido atingir a condição de EV propriamente, a comparação entre grupos foi feita apenas nas três condições, Basal, Relaxamento e Não-EV. Para isso, foi usado o teste de Mann-Whitney U com um limiar estatístico de p<0,05. De forma geral, o GEXP apresentou maior potência na banda de frequência alfa 2 (9,5-11,0 Hz) em todas as condições. Durante o período Não-EV, o GEXP também apresentou uma maior potência na banda de frequência alfa 3 (11,5-13,0 Hz) na região temporal esquerda, e gama 1 (30,5-55,0 Hz) e gama 2 (65,0-80,0 Hz) em regiões central, parietal e temporal esquerda, mas menor potência na banda de frequência teta 1 (3,5 - 5,0 Hz), em regiões centro-parietais. Para a análise estatística intragrupo, entre as condições, utilizou-se o teste estatístico Wilcoxon pareado. Observaram-se diferenças significativas (p<0,005), principalmente em regiões centrais, em teta 1 (3,5-5,0 Hz), sendo maior no Relaxamento, quando comparado com as condições Basal e Não-EV, no GCONT, e com o Não-EV e EV, no GEXP. No GEXP, a potência de gama 1 (30,5-55,0 Hz) e gama 2 (65,0-80,0 Hz) foi difusamente maior durante o EV, se comparado às outras três condições. Para o GCONT, apenas a condição Basal apresentou maior potência de gama 1 (30,5-55,0 Hz) e gama 2 (65,0- 80,0 Hz), se comparado com o Relaxamento. O aumento de teta 1 no Relaxamento, principalmente no GCONT, pode estar associado a uma maior sonolência deste grupo durante esta condição. Já o aumento de alfa 2 durante o Não-EV e o EV, pode estar associado com processos de atenção e cognição (DOLPPERMAYR et al., 2002; FELL et al., 2010; KLIMESCH et al., 1999; RAY E COLE, 1985). Por outro lado, o aumento da potência de gama em sujeitos experientes na técnica de EV encontrado aqui e em trabalhos anteriores, em meditadores experientes (FELL et al., 2010; LEHMANN et al., 2001; LUTZ et al., 2004), poderia estar associado a alterações nos processos mentais e cognitivos destes praticantes, tais como atenção, memória operacional, aprendizagem e percepção consciente embora, análises adicionais devam ser realizadas para excluir a possibilidade de interferência de artefatos musculares nos dados de EEG. Estes resultados suscitam a hipótese de que no engajamento da tarefa do EV e durante o EV, os sujeitos do GEXP conseguem manter-se em um estado de alerta, porém com maior nível de relaxamento e concentração. Uma inspeção mais detalhada dos dados, além de outros experimentos com diferentes protocolos, um maior número de sujeitos e pesquisas longitudinais são necessários para que testar esta hipótese

Níveis de sedação determinados pela clonidina e midazolam na medicação pré-anestésica: avaliação clínica e eletroencefalográfica bispectral

JUSTIFICATIVA E OBJETIVOS: Verificar o efeito sedativo da clonidina, um a2-agonista, e do midazolam, um benzodiazepínico, quando utilizados na medicação pré-anestésica, empregando-se avaliação clínica e eletroencefalográfica bispectral. MÉTODO: Após aprovação institucional e consentimento escrito fornecido, 45 pacientes de 18 a 65 anos, estado físico ASA I, foram aleatoriamente distribuídos nos grupos placebo (P), clonidina (C) ou midazolam (M), em que receberam, respectivamente placebo, 150 µg de clonidina ou 15 mg de midazolam por via oral, 60 minutos antes da indução da anestesia (n = 15 por grupo). A monitorização constituiu-se de eletrocardiograma (D II), pressão arterial não invasiva, freqüência cardíaca, saturação de pulso de oxigênio, freqüência respiratória, temperatura axilar e da sala de cirurgia e eletroencefalograma bispectral para determinação do índice bispectral (BIS). Esses atributos e a escala de sedações (1 - ansioso, 2 - calmo, 3 - sonolento, 4 - dormindo com reflexo, 5 - dormindo sem reflexo) foram obtidos aos 0 (M0), 15 (M15), 30 (M30), 40 (M40), 50 (M50) e 60 (M60) minutos após a medicação. RESULTADOS: Nos grupos não houve alteração significante dos parâmetros respiratórios, hemodinâmicos e de temperatura. Houve diferença significante entre os grupos na ES (M60: M=C>P) e no BIS (M50 e M60: M=C>P). CONCLUSÕES: Nas condições utilizadas, a clonidina e o midazolam determinaram níveis de sedação adequados e semelhantes na medicação pré-anestésica de pacientes estado físico ASA I, quando avaliados pela escala de sedação e pelo índice bispectral, sem determinarem alterações hemodinâmicas e respiratórias.

Topography-specific spindle frequency changes in Obstructive Sleep Apnea

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)