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Estrutura central do hipocampo, o corno de Ammon pode ser subdividido em pelo menos três áreas: CA1, CA2 e CA3. Enquanto CA1 e CA3 foram extensamente estudados, dado o envolvimento do hipocampo em processos cognitivos como a memória e patológicos como a epilepsia, CA2 tem sido largamente ignorado na literatura. Entretanto, este campo possui características específicas, tanto neuroanatômicas como bioquímicas e fisiológicas, sendo resistente à indução de plasticidade e recebendo aferência específica do núcleo supramamilar do hipotálamo, envolvido na circuitaria geradora/mantenedora do ritmo teta, oscilações centrais ao funcionamento do hipocampo. O objetivo deste estudo foi, portanto, caracterizar no animal em livre movimentação os padrões de atividade eletrofisiológica nas três áreas do corno de Ammon bilateralmente. Os resultados demonstraram que CA2 possui, em média, intervalos entre disparos mais prolongados que CA1 e CA3 durante o sono de ondas lentas e o sono REM. Nestas fases do ciclo a coerência entre CA1-CA2 foi mais elevada que entre CA1-CA3 e CA2-CA3 nos três ratos avaliados, em três faixas de freqüência: teta (6 a 12 Hz), gama lento (30 a 50 Hz) e gama rápido (90 a 110 Hz) ipsilateralmente. A coerência entre campos contralaterais é predominante no teta, sendo quase zero nas demais freqüências. Estes resultados corroboram trabalhos recentes que apontam CA2 como área distinta e sugerem que esta pequena região do corno de Ammon possa exercer papéis importantes na modulação da atividade das demais estruturas hipocampais e parahipocampais em processos de memória e em patologias como a epilepsia / The Ammons horn, central structure of the hippocampus, can be subdivided in at least three regions: CA1, CA2 and CA3. While CA1 and CA3 have been extensively studied given the hippocampus involvement in cognitive processes such as memory and pathological ones such as epilepsy, CA2 remains largely ignored. However, this sector contains specific neuroanatomical, biochemical e physiological characteristics, being resistant to induction of plasticity and receiving a specific afference from the supramammillary nucleus in the hypothalamus, involved in the generation/maintenance of the theta rhythm, central oscillations to hippocampal functioning. Therefore, the objective of this study was to characterize electrophysiological patterns of interaction in the three areas of the Ammons horn bilaterally. Results revealed that CA2 has a mean interspike interval larger than CA1 and CA3 during slow wave and REM sleep. During these stages of the sleep-wake cycle, coherence between CA1-CA2 was higher than CA1-CA3 and CA2-CA3 in the three animals evaluated, in three frequency bands: theta (6 to 12 Hz), slow gamma (30 to 50 Hz) and fast gamma (90 to 110 Hz) ipsilaterally. Coherence between contralateral fields was predominant in the theta band and almost zero in other frequencies. These results add to some previous published data showing that CA2 is distinct from the other subfields and that this small region of the Ammons horn may exert important roles in modulating activity in the other hippocampal fields and parahippocampal regions during memory and pathologies such as epilepsy

This thesis provides a novel dynamic large-scale network perspective on brain activity of human sleep based on the analysis of unique human neuroimaging data. Specifically, I provide new information based on integrating spatial and temporal aspects of brain activity both in the transitions between and during wakefulness and various stages of non-rapid-eye movement (NREM) sleep. This is achieved through investigations of inter-regional interactions, functional connectivity (FC), between activity timecourses throughout the brain. Overall, the presented findings provide new important whole-brain insights for our current understanding of sleep, and potentially also of sleep disorders and consciousness in general. In Chapter 2 I present a robust global increase in similarity between the structural connectivity (SC) and the FC in slow-wave sleep (SWS) in almost all of the participants of two independent fMRI datasets. This could point to a decreased state repertoire and more rigid brain dynamics during SWS. Chapter 2 further identifies the changes in FC strengths between wakefulness and individual stages of NREM sleep across the whole-brain fMRI network. I report connectivity in posterior parts of the brain as particularly strong during wakefulness, while connections between temporal and frontal cortices are increased in strength during N1 and N2 sleep. SWS is characterised by a global drop in FC. In Chapter 3 I take advantage of rare MEG recordings of NREM sleep to show, for the first time, the feasibility of constructing source-space FC networks of sleep using power envelope correlations. The increased temporal information of MEG signals allows me to identify the specific frequencies underlying the FC differences identified in Chapter 2 with fMRI. The beta band (16 – 30 Hz) thus stands out as important for the strong posterior connectivity of wakefulness, while a range of frequency bands from delta (0.25 – 4 Hz) to sigma (13 – 16 Hz) all appear to contribute to N2-specific FC increases. Consistent with the fMRI results, slow-wave sleep shows the lowest level of FC. Interestingly, however, the MEG signals suggest a fronto-temporal network of high connectivity in the alpha band, possibly reflecting memory processes. In Chapter 4 I expand the within-frequency FC analysis of Chapter 3 to explore potential cross-frequency interactions in the MEG FC networks. It is shown that N2 sleep involves an abundance of frequency cross-talk, while SWS includes very little. A multi-layer network approach shows that the gamma band (30 – 48 Hz) is particularly integrated in wakefulness. Chapter 5 addresses the identified MEG FC findings from the perspective of traditional spectral sleep staging. By correlating temporal changes in spectral power at the sensor level to fluctuations in average FC, a specific type of transient events is found to underlie the strong N2-specific coupling in static FC values. Lastly, in Chapter 6 I make the leap out of the constraints of traditional low-resolution sleep staging, and extract dynamic states of FC from fMRI timecourses in a completely unsupervised fashion. This provides a novel representation of whole-brain states of sleep and the dynamics governing them. I argue that data-driven approaches like this are necessary to fully characterise the spatiotemporal principles underlying wakefulness and sleep in the human brain.

Estrutura central do hipocampo, o corno de Ammon pode ser subdividido em pelo menos três áreas: CA1, CA2 e CA3. Enquanto CA1 e CA3 foram extensamente estudados, dado o envolvimento do hipocampo em processos cognitivos como a memória e patológicos como a epilepsia, CA2 tem sido largamente ignorado na literatura. Entretanto, este campo possui características específicas, tanto neuroanatômicas como bioquímicas e fisiológicas, sendo resistente à indução de plasticidade e recebendo aferência específica do núcleo supramamilar do hipotálamo, envolvido na circuitaria geradora/mantenedora do ritmo teta, oscilações centrais ao funcionamento do hipocampo. O objetivo deste estudo foi, portanto, caracterizar no animal em livre movimentação os padrões de atividade eletrofisiológica nas três áreas do corno de Ammon bilateralmente. Os resultados demonstraram que CA2 possui, em média, intervalos entre disparos mais prolongados que CA1 e CA3 durante o sono de ondas lentas e o sono REM. Nestas fases do ciclo a coerência entre CA1-CA2 foi mais elevada que entre CA1-CA3 e CA2-CA3 nos três ratos avaliados, em três faixas de freqüência: teta (6 a 12 Hz), gama lento (30 a 50 Hz) e gama rápido (90 a 110 Hz) ipsilateralmente. A coerência entre campos contralaterais é predominante no teta, sendo quase zero nas demais freqüências. Estes resultados corroboram trabalhos recentes que apontam CA2 como área distinta e sugerem que esta pequena região do corno de Ammon possa exercer papéis importantes na modulação da atividade das demais estruturas hipocampais e parahipocampais em processos de memória e em patologias como a epilepsia / The Ammons horn, central structure of the hippocampus, can be subdivided in at least three regions: CA1, CA2 and CA3. While CA1 and CA3 have been extensively studied given the hippocampus involvement in cognitive processes such as memory and pathological ones such as epilepsy, CA2 remains largely ignored. However, this sector contains specific neuroanatomical, biochemical e physiological characteristics, being resistant to induction of plasticity and receiving a specific afference from the supramammillary nucleus in the hypothalamus, involved in the generation/maintenance of the theta rhythm, central oscillations to hippocampal functioning. Therefore, the objective of this study was to characterize electrophysiological patterns of interaction in the three areas of the Ammons horn bilaterally. Results revealed that CA2 has a mean interspike interval larger than CA1 and CA3 during slow wave and REM sleep. During these stages of the sleep-wake cycle, coherence between CA1-CA2 was higher than CA1-CA3 and CA2-CA3 in the three animals evaluated, in three frequency bands: theta (6 to 12 Hz), slow gamma (30 to 50 Hz) and fast gamma (90 to 110 Hz) ipsilaterally. Coherence between contralateral fields was predominant in the theta band and almost zero in other frequencies. These results add to some previous published data showing that CA2 is distinct from the other subfields and that this small region of the Ammons horn may exert important roles in modulating activity in the other hippocampal fields and parahippocampal regions during memory and pathologies such as epilepsy

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. / As demonstrated by recent advancements in the field of neuroscience, sleep is an active and dynamic state in which cohesive neural oscillations organize brain functions. Sleep spindles and slow waves are hallmarks of non-rapid eye movement (NREM) sleep and are used as markers on the electroencephalogram to characterize the underlying neural activity. Because of their implication in sleep and cognitive processes, these oscillations are particularly relevant in aging research, as functional challenges to sleep and memory are well known among this population. Normal aging not only reduces the characteristics of NREM sleep oscillations, but it also modifies anatomical and functional measures of brain integrity. Local regulation of NREM sleep oscillations have recently been described, yet few evidence is currently available on this process in aging. The present work aims to characterize the relationship between sleep neurophysiology, normal aging and regional brain activity with the assessment of the topography and hemodynamics of NREM sleep oscillations throughout adulthood. In a first study, sleep spindle density, duration, amplitude and frequency will be assessed in three age groups in relation to brain topography using electroencephalography. In a second study, hemodynamic responses to slow wave events and their modulation by amplitude will be assessed in two age groups using electroencephalography combined with functional magnetic resonance imaging. Our results can be summarized as follows: 1) age effects on sleep spindle characteristics showed an intriguing dichotomy between anterior and posterior cortical areas; 2) hemodynamic variations related to slow waves were observed in a wide array of cortical and subcortical regions in older individuals. These results suggest the functional reorganization of neural activity during NREM sleep throughout adulthood, support NREM sleep oscillations as useful and sensible biomarkers of brain aging, and promote further research on age-related changes in synaptic plasticity, cell restoration and sleep maintenance.

The master´s thesis is focused on advanced scoring of sleep data, which was performed using deep neural network. Heart rate data and the movement information were used for scoring measured using an Apple Watch smartwatch. After appropriate pre-processing, this data serves as input parameters to the designed networks. The goal of the LSTM network was to classify data into either two groups for sleep and wake or into three groups for wake, Non-REM and REM. The best results were achieved by network doing classification of sleep vs. wake using the accelerometer. The statistical evaluation of this best-designed network reached the values of sensitivity 71,06 %, specificity 57,05 %, accuracy 70,01 % and F1 score 81,42 %.

Slow-wave sleep plays an important role in consolidation of declarative memory. From electrophysiological point of view, this process is dependent on a common occurrence and mutual integration of neocortical slow oscillations (< 1 Hz), hippocampal sharp-wave ripples (150-250 Hz) and thalamo-cortical sleep spindles (10-15 Hz). Previous studies demonstrated that periodic acoustic stimulation by pink noise pulses applied at frequency of sleep slow oscillation during slow wave sleep leads to prolongation of slow wave sleep and to enhancement in declarative memory performance in normal sleepers. Our study investigated this kind of periodic acoustic stimulation in its relation to sleep architecture and declarative memory of people suffering from insomnia due to which there often comes to a reduction in slow wave sleep which positively correlates with worsening of declarative memory performance. Our aim was to investigate if this kind of comparatively non-invasive brain stimulation has a potential to increase a total length of slow wave sleep and enhance declarative memory performance in insomnia. Our study revealed acoustic stimulation neither improved declarative memory performance nor it increased total length of slow-wave sleep. No positive association was found between level of declarative memory...