Gamma oscillations of local field potentials (LFP) in the basal ganglia and thalamus had not been studied during saccades. Eleven patients were studied during deep brain stimulation (DBS); 6 were in the subthalamic nucleus (STN); 3 in the globus pallidus interna (GPi); and 2 in the thalamic ventralis intermedius nucleus (Vim). Patients performed horizontal saccades to visual targets while LFPs from DBS electrodes, scalp electroencephalogram (EEG), and electrooculogram (EOG) were recorded. Wavelet spectrograms were generated and saccade onset and event-related gamma synchronizations (ERS) were compared to baseline without eye motion. ERS were recorded at and after saccade onset in the STN, GPi and Vim, EEGs and EOGs; but were absent during target light illumination without saccades. ERS were symmetric in all DBS contacts and appeared identical in DBS LFPs, frontal EEGs and EOGs. These findings indicate their origin from extraocular muscle spike potentials rather than brain neural activity.

Signals recorded from the brain often show rhythmic patterns at different frequencies, which are tightly coupled to the external stimuli as well as the internal state of the subject. These signals also have transient structures related to spiking or sudden onset of a stimulus, which have a duration not exceeding tens of milliseconds. Further, brain signals are highly non-stationary because both behavioral state and external stimuli can change over a short time scale. It is therefore essential to study brain signals using techniques that can represent both rhythmic and transient components of the signal. In Chapter 2, we describe a multi-scale decomposition technique based on an over-complete dictionary called matching pursuit (MP), and show that it is able to capture both sharp stimulus-onset transient and sustained gamma rhythm in local field potential recorded from the primary visual cortex. Gamma rhythm (30 to 80 Hz), often associated with high-level cortical functions, has been proposed to provide a temporal reference frame (“clock”) for spiking activity, for which it should have least center frequency variation and consistent phase for extended durations. However, recent studies have proposed that gamma occurs in short bursts and it cannot act as a reference. In Chapter 3, we propose another gamma duration estimator based on matching pursuit (MP) algorithm, which is tested with synthetic brain signals and found to be estimating the gamma duration efficiently. Applying this algorithm to real data from awake monkeys, we show that the median gamma duration is more than 330 ms, which could be long enough to support some cortical computations.

Made available in DSpace on 2014-12-17T15:28:49Z (GMT). No. of bitstreams: 1 RobsonST_DISSERT.pdf: 350196 bytes, checksum: eaf6055553dc1f6cec39e0f754c20635 (MD5) Previous issue date: 2011-12-02 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Brain oscillation are not completely independent, but able to interact with each other through cross-frequency coupling (CFC) in at least four different ways: power-to-power, phase-to-phase, phase-to-frequency and phase-to-power. Recent evidence suggests that not only the rhythms per se, but also their interactions are involved in the execution of cognitive tasks, mainly those requiring selective attention, information flow and memory consolidation. It was recently proposed that fast gamma oscillations (60 150 Hz) convey spatial information from the medial entorhinal cortex to the CA1 region of the hippocampus by means of theta (4-12 Hz) phase coupling. Despite these findings, however, little is known about general characteristics of CFCs in several brain regions. In this work we recorded local field potentials using multielectrode arrays aimed at the CA1 region of the dorsal hippocampus for chronic recording. Cross-frequency coupling was evaluated by using comodulogram analysis, a CFC tool recently developted (Tort et al. 2008, Tort et al. 2010). All data analyses were performed using MATLAB (MathWorks Inc). Here we describe two functionally distinct oscillations within the fast gamma frequency range, both coupled to the theta rhythm during active exploration and REM sleep: an oscillation with peak activity at ~80 Hz, and a faster oscillation centered at ~140 Hz. The two oscillations are differentially modulated by the phase of theta depending on the CA1 layer; theta-80 Hz coupling is strongest at stratum lacunosum-moleculare, while theta-140 Hz coupling is strongest at stratum oriens-alveus. This laminar profile suggests that the ~80 Hz oscillation originates from entorhinal cortex inputs to deeper CA1 layers, while the ~140 Hz oscillation reflects CA1 activity in superficial layers. We further show that the ~140 Hz oscillation differs from sharp-wave associated ripple oscillations in several key characteristics. Our results demonstrate the existence of novel theta-associated high-frequency oscillations, and suggest a redefinition of fast gamma oscillations / As oscila??es cerebrais n?o s?o completamente independentes, mas capazes de interagir umas com as outras atrav?s de acoplamentos entre frequ?ncias (cross-frequency coupling, doravante CFC) em pelo menos quatro diferentes modalidades: amplitudeamplitude, fase-fase (coer?ncia), fase-frequ?ncia e fase-amplitude. Evid?ncias recentes sugerem que n?o somente os ritmos per se, mas tamb?m as intera??es entre eles est?o envolvidas na execu??o de tarefas cognitivas, principalmente aquelas que requerem aten??o seletiva, transmiss?o de informa??es e consolida??o de mem?rias. Estudos recentes prop?em que oscila??es gama alto (60 150 Hz) transferem informa??es espaciais do c?rtex entorrinal medial para a regi?o CA1 do hipocampo atrav?s do acoplamento com a fase de teta (4 12 Hz). Apesar destas descobertas, entretanto, pouco se sabe sobre as caracter?sticas gerais dos CFCs em diversas regi?es cerebrais. Neste trabalho, registramos potenciais de campo local usando matrizes de multieletrodos implantadas no hipocampo dorsal para registro neural cr?nico. O acoplamento fase-amplitude foi avaliado por meio da an?lise de comodulogramas, uma ferramenta de CFC desenvolvida recentemente (Tort et al. 2008, Tort et al. 2010). Todas as an?lises de dados foram realizadas em MATLAB (MathWorks Inc). Descrevemos duas oscila??es funcionalmente distintas dentro da faixa de frequ?ncia de gama, ambas acopladas ao ritmo teta durante explora??o ativa e sono REM: uma oscila??o com um pico de atividade em ~80 Hz e uma mais r?pida centrada em ~140 Hz. As duas oscila??es s?o diferencialmente moduladas pela fase de teta conforme a camada de CA1; o acoplamento teta-80 Hz ? mais forte no stratum lacunosum-moleculare, enquanto que o acoplamento teta-140 Hz ? mais forte no stratum oriens-alveus. Este perfil laminar sugere que a oscila??o de 80 Hz origina-se das entradas do c?rtex entorrinal para as camadas profundas de CA1, e que a oscila??o de 140 Hz reflete a atividade de CA1 em camadas superficiais. Ademais, n?s mostramos que a oscila??o de 140 Hz difere-se das oscila??es ripples associadas com sharp-waves em diversos aspectos chave. Nossos resultados demonstram a exist?ncia de novas oscila??es de alta frequ?ncia associadas ? teta e sugerem uma redefini??o das oscila??es gama alto

La perception menant à une prise de décision implique de multiples aires corticales. Il a été proposé que l'information sensorielle se propage des aires sensorielles primaires, codant principalement la nature du stimulus, aux aires de haut-niveau - plus frontales - codant d'avantage la valence du stimulus ou la décision. Pour mieux comprendre l'intégration corticale des signaux sensoriels, nous avons enregistré les réponses sensorielles évoquées (RSE) simultanément dans différentes aires corticales, tandis que des souris apprenaient une tâche de détection sensorielle. Chez les souris ayant appris la tâche, une RSE est observée dans toutes les aires enregistrées suivant la stimulation de la vibrisse, avec des latences croissantes des aires somatosensorielles primaire (vS1) et secondaire (vS2), vers le cortex moteur primaire des vibrisses (vM1), le cortex pariétal associatif (PtA), l'hippocampe dorsal (dCA1) et enfin le cortex préfrontal médian (mPFC). Nous avons constaté une réduction des RSEs lors des échecs par rapport aux essais réussis dans toutes les aires, sauf vS1. Toutefois, seule l'inactivation de vS1, vS2 ou mPFC affecte significativement la performance des souris. Pendant l'apprentissage de la tâche, une augmentation sélective de la RSE est observée dans le mPFC en corrélation avec la performance. Des enregistrements unitaires dans le mPFC démontrent la nature excitatrice de la réponse sensorielle chez les souris entrainées. Nos résultats confirment ainsi que la réponse sensorielle dans le mPFC reflète l'importance comportementale du stimulus et corrèle avec la prise de décision, tandis que la réponse des aires sensorielles reflète plutôt la nature du stimulus / Sensory perception leading to goal-directed behavior involves multiple, spatially-distributed cortical areas. It has been hypothesized that sensory information flows from primary sensory areas encoding mainly the nature of the stimulus, to higher-order, more frontal, areas encoding the valence of the stimulus or the decision. To further understand the cortical integration of sensory signals, we recorded sensory evoked potentials (SEPs) simultaneously from different areas while mice learned a whisker-based sensory detection task. In mice that have learned the task, the whisker stimulus evoked SEP in all recorded areas with latencies increasing from the whisker primary (wS1) to the secondary somatosensory area (wS2), the whisker motor area (wM1), the parietal area (PtA), the dorsal hippocampus (dCA1) and the medial prefrontal cortex (mPFC). We found a reduction of SEPs during Miss trials compared with Hit trials in all areas except wS1. However, only the local inactivation of either wS1, wS2 or mPFC significantly impaired the mice performance. During training to the detection task, we observed a selective increase of the SEPs in mPFC that correlated with performance. Finally, using high-density extracellular recordings in mPFC, we found that whisker stimulation in trained mice evoked an early increase in the firing rate of putative excitatory neurons (regular spiking units) that was positively correlated with behavioral outcome. Our results support the idea that mPFC could signal the relevance of a sensory stimulus in the context of a well-defined behavior, whereas sensory areas would be more constrained by the nature of the stimulus

L’incertitude est un processus cognitif communément expérimenté lors d’une prise de décision. Dansle trouble obsessionnel-compulsif (TOC), il est excessif et compromet les capacités décisionnelles del'individu.Ce travail avait comme objectif une meilleure compréhension des aspects physiologiques etphysiopathologiques de l’incertitude, au travers d'une double approche, comportementale etélectrophysiologique. Dans un premier temps, nous avons construit une tâche originale qui permetd'exprimer son incertitude au cours d'une prise de décision. Avec cette "tâche d’incertitude", nousavons exploré les relations entre mémoire de travail et incertitude. Nous avons montré que lescapacités de mémoire de travail prédisaient la propension à l'incertitude chez les volontaires sains alorsque l'incertitude était suivie d'une dégradation des performances mnésiques chez les patients TOC.Puis, nous avons trouvé une relation entre capacités mnésiques et incertitude dans une population depatients épileptiques caractérisée par des déficits mnésiques, confirmant ainsi le rôle des capacitésmnésiques dans la survenue de l'incertitude physiologique.Pour l'étude des corrélats neuronaux, nous avons mesuré l'activité électrophysiologique intracérébraledes régions impliquées dans la prise de décision au cours de la tâche d'incertitude, chez des patientsépileptiques pour les structures corticales et chez des patients TOC pour les structures sous-corticales.Nous avons montré que l'incertitude était associée à : 1/ une diminution d’amplitude des potentielsévoqués des régions préfrontales et prémotrices ; 2/ une moindre synchronisation des bandes defréquence alpha et bêta en temps-fréquence ; 3/ une augmentation de l'amplitude des potentielsévoqués dans le noyau sous-thalamique. Nos résultats suggèrent un défaut d'engagement des structurescorticales impliquées dans la prise de décision au cours de l'incertitude. Enfin, notre travail tend àconfirmer le rôle du noyau sous-thalamique dans la physiopathologie du TOC et dans les mécanismessous-tendant l’incertitude pathologique. / Uncertainty is a cognitive process that frequently influences our decisions in everyday life. Inobsessive-compulsive disorder (OCD), the high level of uncertainty usually alters the decision-makingprocess.This work aimed to a better understanding of physiological and pathophysiological aspects ofuncertainty, by exploring its relationships with working memory abilities and its neural correlates. Anoriginal task derived from a delayed matching-to-sample task was created with the possibility toexpress felt uncertainty during decision-making. With this "uncertainty task", we demonstrated thatbaseline working memory abilities predicted the occurrence of uncertainty in healthy individualswhereas uncertainty was followed by a decrease in working memory abilities in OCD patients. Therole of working memory abilities in the occurrence of uncertainty was further confirmed in a clinicalpopulation of epileptic patients suffering from baseline working memory impairments.For the study of the neural correlates of uncertainty, we measured intracerebral local field potentials(LFPs) in regions involved in decision-making during the uncertainty task. Cortical and subcorticalLFPs were obtained in epileptic and OCD patients, respectively. We showed that uncertainty wasassociated with: 1/ a decreased amplitude of evoked responses in cortical prefrontal and premotorregions, 2/ a reduced synchronization of alpha-beta frequency bands in time-frequency analyses, 3/ anincreased amplitude of evoked responses in the subthalamic nucleus. Our findings suggested adiminished cortical activation in uncertain decision-making and confirmed the role of the subthalamicnucleus in OCD pathophysiology and in the mechanisms underlying the occurrence of pathologicaluncertainty.

While signatures of attention can be observed in widespread areas within and outside of cortex, the control of attention is thought to be regulated by higher cognitive brain areas, such as the prefrontal cortex. In their recent study on mice Kim et al. could show that successful allocation of attention is characterized by increased spiking of a specific type of inhibitory interneurons, the parvalbumin neurons, and higher oscillatory activity in the gamma band in the local prefrontal network. It was recently demonstrated that encoding of working memory in prefrontal areas is linked to bursts of gamma oscillations, a discontinuous network process characterized by short periods of intense power in the gamma band. The relationship between attention and working memory is unclear, and it is possible that these two cognitive processes share encoding principles. To address this gap, the electrophysiological data collected in the Carlén Lab have been analyzed with advanced spatio-temporal approaches. In particular, we have analyzed bursting gamma activity in medial prefrontal cortex during attentional processing and investigated the similarities to gamma bursting observed during working memory. Gamma-band bursts during attention were reliably detected with several methods. We have characterized several features of the bursts, including the occurrence, duration and amplitude. The neuronal firing rates during and outside of bursts have also been computed. We investigated the correlation between different criteria characterizing the gamma burst and successful vs failed allocation of attention. Control data were generated to discuss the obtained results. The aim of the study was to explore the hypothesis that the medial prefrontal cortex encodes attention trough gamma bursts, which could reveal some similarities and differences in coding of central cognitive processes. No clear difference was found in the characterization between successful and failed allocation of attention. In addition, results were very similar in control set and original data. No underlying mechanism could be identified from this analysis. Therefore, as the bursts occurring in the gamma band in the prefrontal cortex (PFC) were not discriminative with respect to the different tested conditions, they do not seem to encode information related to attention. / Även fast flera olika hjärnområdens aktivitet kan korreleras med uppmärksamhet, anses kontrollen av uppmärksamhet regleras av högre kognitiva hjärnområden, såsom främre hjärnbarken. I en nyligen publicerad artikel studerade Kim et al. hjärnaktiviteten hos möss och kunde visa att en framgångsrik uppmärksamhet kännetecknas av en ökad aktivitet av en specifik typ av inhiberande nervceller, parvalbumin celler, och högre oscillerande aktivitet i gammafrekvens i främre hjärnbarkens lokala nätverk. Det har nyligen visats att kodning av arbetsminne i främre hjärnbarken är kopplat till utbrott av gamma-oscillationer, en diskontinuerlig nätverksprocess som kännetecknas av korta perioder av intensiva oscillationer av det lokala nätverket i gammafrekvens . Relationen mellan uppmärksamhet och arbetsminne är oklar, och det är möjligt att dessa två kognitiva processer delar kodningsprinciper. För att minska detta gap av kunskap har den elektrofysiologiska datan som samlats in i Carlén Lab analyserats med avancerade spatio-temporala tillvägagångssätt. I synnerhet har vi analyserat utbrott i gammaaktivitet i främre hjärnbarken under uppmärksamhet och undersökt likheterna med gamma- utbrott observerade under arbetsminne. Gamma-bandutbrott under uppmärksamhet påvisades på ett tillförlitligt sätt med flera metoder. Vi har karaktäriserat flera funktioner hos utbrotten, inklusive förekomsten, varaktigheten och amplituden. De enskilda cellernas aktivitet undersöktes även under och utanför utprotten av gamma-oscillationer. Vi undersökte sambandet mellan de olika kriterier som karakteriserar gamma-utbrott under framgångsrik mot misslyckad allokering av uppmärksamhet. Kontrolldata genererades för att diskutera de erhållna resultaten. Syftet med studien var att utforska hypotesen att den främre hjärnbarken kodar uppmärksamhet genom gamma-utbrott, vilket kan avslöja vissa likheter och skillnader i kodning av centrala kognitiva processer. Ingen klar skillnad hittades i karaktäriseringen mellan framgångsrik och misslyckad allokering av uppmärksamhet. Dessutom var resultaten mycket likartade i kontrolluppsättningen och den ursprungliga datan. Ingen underliggande mekanism kunde identifieras ur denna analys. Eftersom de utbrott som uppstod i gamma-bandet i främre hjärnbarken inte var unika med hänsyn till de olika testade förhållandena, tycks de därför inte koda information relaterad till uppmärksamhet.

No description available.

Le travail de recherche réalisé au cours de cette thèse s'intéresse à la nature des représentations spatiales formées par le cortex entorhinal médian (CEM). Tout d'abord, nous montrons que le CEM code spécifiquement une information de distance, l'une des composantes nécessaires pour que l'animal puisse réaliser un type de navigation reposant sur les informations idiothétiques, appelé intégration des trajets. Puis, nous observons que le système vestibulaire, une source importante d'informations idiothétiques, influence l'activité thêta du CEM et permet la modulation de ce rythme thêta par la vitesse de déplacement des animaux. Ensuite, nous montrons que l'activité du CEM est nécessaire à la stabilité de l'activité des cellules de lieu. Parallèlement, nous observons que l'activité des cellules grilles du CEM est modifiée par les informations contenues dans l'environnement (allothétiques).Dans leur ensemble, nos résultats montrent que le CEM traite et intègre des informations idiothétiques mais aussi des informations allothétiques. Ces données suggèrent que la carte spatiale du CEM ne fournit pas une métrique universelle reposant sur les informations idiothétiques, mais possède un certain degré de flexibilité en réponse aux changements environnementaux. De plus, cette carte spatiale entorhinale n'est pas requise pour la formation de l'activité spatiale des cellules de lieu, contrairement à ce que suggère l'hypothèse dominante. / The work conducted during my PhD thesis was aimed at understanding the nature of the spatial representation formed by the the medial entorhinal cortex (MEC). First, we show that the MEC codes specifically distance information which is necessary for a type of navigation based on idiothetic cues, called path integration. Then, we observe that the vestibular system, an important source of idiothetic information in the brain, influences the MEC theta rhythm and its modulation by the animal velocity. In addition, we show that MEC activity is necessary for the stability of place cells activity. Finally, we observe that entorhinal grid cells activity is modified by the information available in the environment (allothetic information).Together, our results show that the MEC processes and integrates idiothetic information as well as allothetic information. These data suggest that the entorhinal map is not a universal metric based on idiothetic information, but is flexible and dependant on the information present in the environment. In addition, the entorhinal map is not required for the generation of place cells activity, contrary to the dominant hypothesis.