Working memory, which enables the temporary storage of information in an active “online” state, is an exceptionally capacity limited system. Given this capacity limit, irrelevant information in our environment must be filtered out, while relevant representation is maintained. Research has shown that neural oscillations in the alpha frequency range (8-12Hz) are greatly influenced by the number of items in memory. Most work has argued that alpha oscillations primarily support working memory processing by suppressing information that could interfere with items already in memory, as indexed by an increase in alpha power. However, other work has shown that decreases in alpha power, with little evidence of concurrent increases, support the maintenance of working memory representations. In this thesis we show that, in the context of visual working memory, the primary role of alpha oscillations is to maintain distinct working memory representations, rather than to suppress irrelevant information. This is shown in a series of three experiments all indicating that as the number of relevant items increases, the power of alpha oscillations systematically decreases. In the first experiment, we use a whole report and change detection task to examine how the number of items in memory influences alpha oscillations. In the second experiment, we use a cuing (Experiment 2A) and filtering (Experiment 2B) paradigm to demonstrate that alpha power tracks the number of remembered items instead of the number of total items on the screen. Lastly, by presenting items sequentially (Experiment 3A) or in overlapping locations (Experiment 3B), we see evidence that decreases in alpha power are related to the maintenance of relevant spatial locations, instead of the number of items in memory. The results of the experiments suggest that alpha power reflects the maintenance of relevant working memory representations, rather than the suppression of irrelevant external distractors or the inhibition of task-irrelevant neural areas. Furthermore, our last experiment indicates that the alpha frequency band is especially sensitive to the maintenance of spatial information.

Alpha oscillations (8-13 Hz) have been suggested to play an important role in dynamic neural processes underlying learning and memory. The goal of this work was to scrutinize the role of alpha oscillations in communication within a cortico-cerebellar network implicated in motor sequence learning. To this end, we conducted two EEG experiments using a serial reaction time task. In the first experiment, we explored changes in alpha power and cross-channel alpha coherence as subjects learned a motor sequence. We found a gradual decrease in spectral alpha power over left premotor cortex (PMC) and sensorimotor cortex (SM1) during learning blocks. In addition, alpha coherence between left PMC/SM1 and left cerebellar crus I was specifically decreased during sequence learning, possibly reflecting a functional decoupling in the broader motor learning network. In the second experiment in a different cohort, we applied 10Hz transcranial alternating current stimulation (tACS), a method shown to entrain local oscillatory activity, to left M1 (lM1) and right cerebellum (rCB) during sequence learning. We observed a tendency for diminished learning following rCB tACS compared to sham, but not following lM1 tACS. Learning-related alpha power following rCB tACS was increased in left PMC, possibly reflecting increase in local inhibitory neural activity. Importantly, learning-specific alpha coherence between left PMC and right cerebellar lobule VIIb was enhanced following rCB tACS. These findings provide strong evidence for a causal role of alpha oscillations in controlling information transfer in a premotor-cerebellar loop during motor sequence learning. Our findings are consistent with a model in which sequence learning may be impaired by enhancing premotor cortical alpha oscillation via external modulation of cerebellar oscillations.:1 List of Abbreviations 2 Introduction 2.1 Motor Learning Stages 2.2 Motor Learning Tasks 2.3 Motor Learning Network 2.4 Theoretical Models of Motor Learning 2.5 Functional Connectivity of Motor Brain Regions 2.6 Effective Connectivity of Motor Brain Regions 2.7 Oscillations in Neuronal Communication 2.8 Alpha Oscillations 2.8.1 Role of Alpha Oscillations in Motor Sequence Learning 2.9 Transcranial Electric Stimulation 2.9.1 Transcranial Alternating Current Stimulation (tACS) 2.10 Summary of Study Rationale 3 Publication 4 Summary 5 List of References 6 Supplementary Materials 7 Contribution of Authors / Darstellung des eigenen Beitrags 8 Declaration of Authorship 9 Curriculum Vitae 10 Publication and Presentation 11 Acknowledgement / Danksagung

Des réactions inhabituelles et disproportionnées face aux changements survenant de manière imprévisible dans l’environnement sont observées dans l’autisme. L’objectif de ce travail est de caractériser chez des adolescents et des jeunes adultes avec autisme les mécanismes neurophysiologiques impliqués dans le traitement d’un contexte visuel prédictif à partir de l’analyse des potentiels évoqués et des oscillations cérébrales. L’étude de la maturation au cours de l’adolescence chez le sujet au développement typique montre que les mécanismes de prédiction sont matures dès l’âge de 12 ans. Les personnes avec autisme parviennent à extraire l’information pertinente dans un contexte simple, certain et explicite, et à l’utiliser pour se préparer à la survenue d’un événement afin d’y avoir une réponse adaptée. Ces résultats suggèrent que les mécanismes de traitement d’un contexte visuel prédictif dans un contexte certain sont préservés dans l’autisme. Toutefois, les personnes avec autisme sur-anticipent les stimulations imprévisibles, en accord avec leur impression de surcharge sensorielle. Elles présentent également des difficultés pour moduler de manière flexible les activités corticales en fonction du niveau d’incertitude du contexte, en accord avec le défaut d’adaptation à un monde en perpétuel changement. Ce travail suggère qu’un dysfonctionnement des mécanismes de prédiction dans un contexte incertain pourrait fournir un cadre théorique permettant de mieux comprendre les particularités rencontrées dans l'autisme. / Individuals with autism react in an unusual and disproportionate way if unpredictable changes occur in their environment. The aim of the present work is to investigate brain mechanisms involved in visual predictive context processing in adolescents and adults with autism using analysis of event-related potentials and brain oscillations. The developmental study shows that mechanisms of prediction are mature by the age of 12 in typically developing adolescents. Individuals with autism are able to extract relevant information from the stimulus train in a simple, certain and explicit context, to use it in order to anticipate the occurrence of an event and to have an appropriate response, suggesting preserved extraction and use of predictive information during a certain context. However, individuals with autism over-anticipate stimuli during an uncertain context, consistent with the sense of being overwhelmed by incoming information, and also cannot flexibly modulate cortical activity according to changing levels of uncertainty, in agreement with atypical adaptation in an ever-changing world. This work suggests that a dysfunction of predictive processing in an uncertain context might provide a theoretical framework to better understand the symptoms encountered in autism.

Les mécanismes volontaires (V) et involontaires (I) de l’attention reposent sur les réseaux dorsal et ventral, convergeant dans le cortex préfrontal latéral (lPFC). La distractibilité accrue liée au vieillissement ou à une lésion frontale pourrait être due à une altération de l’équilibre entre ces mécanismes V et I, essentiel mais rarement étudié. Notre objectif est de tester, dans la modalité auditive, si (1) les oscillations alpha coordonnent l'activité du réseau dorsal, (2) les oscillations gamma celle du réseau ventral, (3) le couplage oscillatoire dans le lPFC maintient l’équilibre entre les deux réseaux. Ce travail vise également à étudier les corrélats oscillatoires de la distractibilité accrue liée au vieillissement ou à une atteinte frontale. Des données MEEG ont été enregistrées alors que des participants réalisaient le Competitive Attention Test, qui permet d’étudier simultanément les mécanismes V et I de l’attention. Nous avons montré que les oscillations alpha reflètent l’activation des mécanismes facilitateurs et suppresseurs de l’attention V, et la communication au sein du réseau dorsal ; alors que les oscillations gamma indexent l’activation du réseau ventral. De plus, le lPFC serait impliqué dans la communication au sein des deux réseaux, et le PFC médian dans l’équilibre attentionnel V/I. Nous avons également montré que la distractibilité accrue était liée à un déficit d’attention V au cours du vieillissement, et à une altération des processus V et I après lésion frontale. Ce travail de thèse offre donc une meilleure compréhension de la dynamique cérébrale oscillatoire sur laquelle repose l'équilibre attentionnel V/I, et donc la distractibilité / Top-down (TD) and bottom-up (BU) mechanisms of attention are supported by dorsal and ventral networks that mainly overlap in the lateral prefrontal cortex (lPFC). A balance between these mechanisms is essential, yet rarely investigated. Increased distractibility observed during ageing or after frontal damage could result from jeopardizing this balance. It has been proposed that distinct oscillatory frequencies support the activation of these two attention networks. Our main aim was to test, in the auditory modality, whether (1) alpha oscillations would coordinate activity within the dorsal TD network, (2) gamma activity would index the activation of the ventral BU network, (3) the lPFC would support the balance between these networks through oscillatory coupling. We also aimed to investigate the oscillatory correlates of the increased distractibility associated with ageing or frontal damage. MEEG data were recorded while participants performed the Competitive Attention Test, which enables simultaneous investigation of BU and TD attention mechanisms. We showed that alpha oscillations indexed facilitatory and suppressive mechanisms of TD attention, and communication within the dorsal network; while gamma oscillations indexed the ventral network activation. Moreover, the lPFC subtended communication in the two networks; with the TD/BU interaction occurring in the medial PFC. We also showed that ageing-related distractibility was of TD deficit origin. Finally, preliminary results suggest that lPFC damage can impact both TD and BU attention. This thesis provides novel insights into the brain oscillatory dynamics of the TD/BU attentional balance supporting distractibility