Past research associated relative left frontal cortical activity with approach motivation, or the inclination to move toward a stimulus, as well as positive affect. Work with anger, a negative emotion often high in approach, helped clarify the role of relative left frontal cortical activity. Less work, however, examined positive emotional states varying in approach motivation and relative left frontal cortical activity. In the present research, it was predicted that positive facial expressions varying in degrees of approach motivation would influence relative left frontal cortical activity measured with electroencephalography (EEG) alpha power and task persistence measured with time working on insolvable geometric puzzles. Furthermore, relative left frontal cortical activity should positively relate to task persistence. In support of these predictions, determination compared to satisfaction facial expressions caused greater relative left frontal activity measured with EEG alpha power, a neural correlate of approach motivation. This effect remained when accounting for the contribution of muscle activity in the EEG signal, subjective task difficulty, and the extent to which participants made facial expressions. Determination compared to neutral facial expressions also caused greater self-reported interest following the puzzle task. Facial expressions did not directly influence task persistence. However, relative left frontal cortical activity was positively correlated with total time working on insolvable puzzles in the determination condition only. These results extend embodiment theories and motivational models of asymmetric frontal cortical activity.

Introduction: Anxiety is induced by a perceived threatening situation and can impair the decision-making ability and maintenance of attention on relevant stimuli. The pre-frontal cortex (PFC) has been implicated in anxiety through the multiple network theory however, the PFC’s role in anxiety is poorly understood. Implementing visual perturbations increases PFC activity due to increased attentional demands, which is observed in younger adults. Due to increased attentional processes produced from visual perturbations, cortical activity can be altered. Methods: Twenty healthy young adults performed three treadmill walking tasks, without visual cues, with visual cues and with perturbations. Cortical activity was recorded with a 22-channel, 18 optode fNIRS cap (Dual Brite MKII; Artinis Medical Systems, Netherlands). Anxiety measurements included the state-trait anxiety inventory (Spielberger et al., 1971) and heart rate variability (polar hear rate monitor). A Friedman rank sum test was performed to determine differences observed in heart rate variability RMSSD (HrvRMSSD) and mean oxyhemoglobin concentration change, among gait conditions. Mann-Whitney U tests were used to determine effects of trait anxiety on HrvRMSSD for gait conditions. Spearman rank correlations where ran between anxiety measures and PFC activity. Results: No significant condition effect on mean oxyhemoglobin concentration change (χ2 = 3.9, p = 0.14) was found. There was a significant condition effect for HrvRMSSD (χ2 = 17.2, p < 0.001). Post hoc analysis showed a significant decrease between baseline and stepping (p = 0.003, r = 0.17) and baseline and stepping varied (p = 0.02, r = 0.24). No significant trait anxiety effects found on HrvRMSSD during baseline (p = 0.15), stepping (p=0.20) and stepping varied (p=0.08), between low and moderate trait anxiety. No correlations were found between anxiety measures and PFC activity. Significance: The present experiment shows that PFC activity does not alter in young adults between a gait and visually perturbed gait. Further, we observed no significant change in PFC activity when anxiety, measured by HrvRMSSD, increased with gait condition difficulty. These results did not support our hypotheses, but the results will help inform protocol decisions of future investigations.

No / Until recently, it was widely believed that object position and object motion were represented independently in the visual cortex. However, several studies have shown that adaptation to motion produces substantial shifts in the perceived position of subsequently viewed stationary objects [[13]]. Two stages of motion adaptation have been proposed: an initial stage at the level of V1 and a secondary stage thought to be located in V5/MT [[4]]. Indeed, selective adaptation can be demonstrated at each of these levels of motion analysis [[5, 6]]. What remains unknown is which of these cortical sites are involved in modulating the positional representation of subsequently viewed objects. To answer this question directly, we disrupted cortical activity by using transcranial magnetic stimulation (TMS) immediately after motion adaptation. When TMS was delivered to V5/MT after motion adaptation, the perceived offset of the test stimulus was greatly reduced. In marked contrast, TMS of V1 had no effect on the changes that normally occur in perceived position after motion adaptation. This result demonstrates that the anatomical locus at which motion and positional information interact is area V5/MT rather than V1/V2.

Une des caractéristiques les plus singulières de l’activité corticale est son degré élevé de variabilité. Ma thèse dedoctorat s’est focalisée sur l’étude de (i) l’irrégularité des intervalles entre potentiels d’action (PAs)successivement émis par un neurone, et (ii) la variabilité dans l’évolution temporelle de l’activité d’un ensemblede neurones. Premièrement, j’ai étudié l’irrégularité des neurones enregistrés dans le cortex moteur de singesmacaques performant une tâche d’estimation du temps et de préparation à l’action. J’ai montré que l’irrégularitén’est pas un paramètre libre de l’activité neuronale, contrairement au taux de PAs, mais est déterminée par lescontraintes structurelles des réseaux neuronaux. Deuxièmement, j’ai utilisé le modèle de Markov caché (MMC)pour analyser l’activité d’ensembles de neurones enregistrés dans plusieurs aires corticales, sensorielles etmotrices, de singes exécutant une tâche de discrimination tactile. J’ai montré que les processus sensoriels etdécisionnels sont distribués dans plusieurs aires corticales. Les résultats suggèrent que l’action et la décision surlaquelle elle est basée sont reliées par une cascade d’évènements non stationnaires et stochastiques. Finalement,j’ai utilisé le MMC pour caractériser l’activité spontanée d’un ensemble de neurones du cortex préfrontal d’unrat. Les résultats montrèrent que l’alternance entre les états UP et DOWN est un processus stochastique etdynamique. La variabilité apparaît donc aussi bien pendant l’activité spontanée que pendant le comportementactif et semble être contrainte par des facteurs structurels qui, à leur tour, contraignent le mode d’opération desréseaux neuronaux. / A hallmark of cortical activity is its high degree of variability. The present work focused on (i) the variability ofintervals between spikes that single neurons emit, called spike time irregularity (STI), and (ii) the variability inthe temporal evolution of the collective neuronal activity. First, I studied the STI of macaque motor corticalneurons during time estimation and movement preparation. I found that although the firing rate of the neuronstransmitted information about these processes, the STI of a neuron is not flexible and is determined by thebalance of excitatory and inhibitory inputs. These results were obtained by means of an irregularity measure thatI compared to other existing measures. Second, I analyzed the neuronal ensemble activity of severalsomatosensory and motor cortical areas of macaques during tactile discrimination. I showed that ensembleactivity can be effectively described by the Hidden Markov Model (HMM). Both sensory and decision-makingprocesses were distributed across many areas. Moreover, I showed that decision-related changes in neuronalactivity rely on a noise-driven mechanism and that the maintenance of the decision relies on transient dynamics,subtending the conversion of a decision into an action. Third, I characterized the statistics of spontaneous UP andDOWN states in the prefrontal cortex of a rat, using the HMM. I showed that state alternation is stochastic andthe activity during UP states is dynamic. Hence, variability is prominent both during active behavior andspontaneous activity and is determined by structural factors, thus rending it inherent to cortical organization andshaping the function of neural networks.

Sleep is well-established to become more superficial and fragmented as we age, with deficits in cognitive processing also commonly observed. While effects have been identified in both humans and mice (used in this thesis), there are important species differences in these findings and importantly, very little is known about the neural dynamics underlying these changes. By integrating several state-of-the-art approaches from putative single unit electrophysiological recordings to behavioural and pharmacological assessments, this thesis aimed to provide novel insights into the neural mechanisms involved in the age-dependent changes in sleep and cognition in mice. Firstly, this thesis investigated the neural activity underpinning the known global sleep changes that occur with ageing. Surprisingly, the majority of neuronal measures quantified in this study were resilient to the effects of ageing. Therefore the global sleep disruptions identified with ageing are unlikely to arise from changes in local cortical activity. Secondly, diazepam injection was found to suppress neural activity, in addition to previously reported effects on electroencephalography (EEG). Subtle differences in the effects of diazepam were identified across age groups, which may account for the variability seen in the efficacy of benzodiazepines in older individuals. Thirdly, ageing and sleep deprivation were found to have only a few effects on performance in a spatial learning task, the Morris water maze (MWM). Suggesting that spatial learning may be fairly resilient to the effects of ageing and sleep deprivation. Finally, this thesis presents preliminary analyses that showed mice were able to perform two novel paradigms of the visual discrimination task, suggesting their suitability in studying the link between ageing, sleep and cognition. Together the studies presented in this thesis provide insights into the differences between global and local mechanisms affected by ageing. Only by understanding local mechanisms will we be able improve on current treatments aimed at helping with the unwanted effects of healthy ageing, such as cognitive decline and sleep disruptions.

La transmission cholinergique, et notamment muscarinique, joue un rôle déterminant dans le système nerveux central au niveau de la modulation de la plasticité neuronale. La libération d'ACh dans le cortex visuel est concomitante à la présentation de stimuli visuels. Par son action sur la transmission neuronale corticale, l'ACh module à long terme les réponses à de nouveaux stimuli sensoriels. Dans la présente étude, l'implication du système cholinergique au niveau du développement cortical et de la plasticité inductible chez l'adulte a été étudiée par les techniques d'imagerie optique des signaux intrinsèques et d'immunohistochimie chez le rongeur. Ces deux techniques de cartographie de l'activité corticale nous ont permis d'évaluer, d'une part, l'impact modulatoire de l'acétylcholine (ACh) et de ses récepteurs muscariniques (mAChRs, M1 à M5) sur l'organisation fonctionnelle du cortex visuel chez des souris déficitaires pour les mAChRs et, d'autre part, l'impact de la libération d'ACh lors d'un entraînement visuel, sur le nombre, la nature neurochimique et la localisation au niveau des couches corticales des neurones corticaux activés. L'implication du système cholinergique sur la cartographie du cortex visuel primaire a été étudiée sur les souris génétiquement modifiées délétères (knock out : KO) pour différentes combinaisons de sous-types de mAChRs. L'imagerie des signaux intrinsèques, basée sur les changements de réflectance corticale de la lumière survenant lors de la consommation d'oxygène par les neurones activés, a permis de déterminer, lors de stimulations visuelles, les différentes composantes des propriétés des neurones du cortex visuel. La taille des champs récepteurs des neurones est diminuée lors de l'absence du récepteur M1 ou de la combinaison M1/M3. Le champ visuel apparent est augmenté chez les souris M2/M4-KO mais diminué chez les M1-KO. La finesse des connectivités neuronales (évaluée par la mesure du scatter du signal) est réduite lors de l'absence des récepteurs M2/M4. Finalement, chez les animaux M1/M3-KO, une diminution de l'acuité visuelle est observée. L'effet à long-terme d'un entraînement visuel couplé à une stimulation des neurones cholinergiques sur la distribution et la nature des neurones immunoréactifs au c-Fos, c'est-à-dire les neurones activés, a été évalué. Puisque cette stimulation combinée est en mesure de produire des modifications comportementales, notamment au niveau de l'acuité visuelle, il devenait intéressant de s'attarder aux modifications neuroanatomiques et de déterminer quels éléments de l'équilibre excitateur/inhibiteur sont compromis chez ces animaux. Les résultats obtenus démontrent que les animaux ayant reçu une combinaison de l'entraînement cholinergique et visuel présentent une augmentation du marquage c-Fos comparativement aux animaux n'ayant reçu que la stimulation cholinergique. D'autre part, chez ces animaux, il est possible d'observer des modifications de l'équilibre excitateur/inhibiteur qui correspond au potentiel plastique de la région. En conclusion, ces études démontrent un rôle important du système cholinergique dans le développement, la maturation et la plasticité du système visuel cérébral. / The cholinergic transmission, including the muscarinic receptors, plays a role in the central nervous system modulating neuronal plasticity. ACh is released in the visual cortex during the presentation of visual stimuli. By its action on cortical neuronal transmission, ACh modulates long-term responses to new sensory stimuli. In the present study, the involvement of the cholinergic system in cortical development and inductible plasticity in adults was investigated by optical imaging of intrinsic signals and immunohistochemistry in rodents. These two mapping techniques of cortical activity allowed us to evaluate 1) the modulatory effect of acetylcholine (ACh) and its muscarinic receptors (mAChRs, M1 to M5) on the functional organization of the visual cortex in mice deficient of mAChRs and 2) the impact of ACh release during a visual training on the number, neurochemical nature and location of activated neurons in the cortical layers. The involvement of the cholinergic system on the mapping of the primary visual cortex was studied in mice knockout (KO) for different combinations of mAChRs subtypes. Intrinsic signals imaging, based on fluctuations in cortical light reflectance during oxygen consumption by activated neurons, was used to assess the various properties of neurons in the visual cortex during visual stimulation. The size of the neuronal receptive fields is reduced in the absence of M1 receptor or the combination M1/M3. The apparent visual field is increased in M2/M4-KO mice but decreased in M1-KO. The sharpness of neuronal connectivity (assessed by the measure of the scatter) is reduced in the absence of M2/M4 receptors. Finally, in M1/M3-KO animals, a decrease in visual acuity was observed. The effect of long-term visual training coupled with the stimulation of cholinergic neurons on the distribution and nature of immunoreactive neurons in c-Fos, the activated neurons, was evaluated. Since this combined stimulation is able to produce behavioral changes, especially in terms of visual acuity, it was interesting to focus on neuroanatomical modifications and determine which elements of the excitatory / inhibitory balance were compromised in these animals. The results showed that animals which received a combination of visual and cholinergic training presented an increase in c-Fos labeling compared to animals that received only the cholinergic stimulation. Moreover, in these animals, it is possible to observe changes in the excitatory / inhibitory balance which corresponds to the potential of plasticity in the region. In conclusion, these studies demonstrate an important role of the cholinergic system in the development, maturation and plasticity of the cerebral visual system.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / A espasticidade é observada na maioria dos pacientes após Acidente Vascular Encefálico (AVE), e exercem influência na presença de deficiências e incapacidades, comprometendo a função motora. As estratégias de neuroreabilitação, o biofeedback eletromiográfico (EMG), têm sido utilizado com aceitação na comunidade médica para reajustes nas habilidades sensório-motoras como retreinamento motor, redução da espasticidade e/ou treinamento de relaxamento. A intervenção ainda apresenta evidências delimitadas quanto a sua efetividade na reabilitação, principalmente, quanto a interferência sobre a atividade cortical e na redução dos sinais espásticos que oferece características negativas na execução do movimento. O objetivo dessa pesquisa foi analisar a possível interferência do treino com biofeedback eletromiográfico sobre a conscientização do controle motor no membro espástico e a caracterização da atividade das bandas de baixa frequência em diferentes regiões corticais orientada pela técnica de treinamento. Dezesseis voluntários acometidos por AVE isquêmicos foram selecionados e divididos em dois grupos (n=8). Grupo experimental (GE) submetidos ao treino com biofeedback associado a fisioterapia, e o grupo controle (GC) submetido apenas à fisioterapia convencional. Foi realizada a avaliação do grau de espasticidade pelo limiar de reflexo do estiramento tônico (LRET) e pela Escala Modificada de Ashworth (EMA) antes e três semanas após o término do treinamento com a técnica. Os sujeitos foram submetidos ao biofeedback durante 6 semanas, com 2 sessões semanalmente. O mesmo tempo para o tratamento fisioterápico foi padronizado para o GC. Os resultados mostram variação do percentual médio de melhora do grau de espasticidade, mensuradas pelo LRET, de 38,59% (dp=13,03%) no GE comparado com 18,58% (dp=11,90%) do GC. Essa variação apresentou diferença significativa (p=0,020; t=2,776; p<5%) entre os grupos (controle e experimental), e a diferença significativa do LRET antes e após do treinamento no GE (p=0,003; t=5,338; p<5%) quando comparado ao GC (p=0,015; t=3,657; p<5%). A medida semi-quantitativa da EMA antes e após o término das sessões mostraram variações apenas no GE. Com relação a atividade cortical, houve diferença de atividade das bandas (delta, teta, alfa e beta) quando a 3ª e 12ª sessão foram comparadas para cada sujeito do GE. Essa diferença foi encontrada, principalmente, em regiões frontal, central (vértex), parietal e occipital em ambos hemisférios (ipsilateral e contralateral a lesão) tanto na fase de planejamento cognitivo motor quanto na execução do movimento. Houve predominância da diferença de atividade para a banda delta, alfa e beta em diferentes sujeitos distribuída difusamente ao longo dos canais de registro de viii EEG. A atividade diferenciada das bandas foi devido ao aumento e/ou diminuição da energia espectral entre as sessões, notado apenas em alguns voluntários do GE. Observou ainda diferença de atividade em áreas motoras secundárias. As avaliações, principalmente do LRET mostram que o treino com biofeedback EMG foi efetivo na redução do grau de espasticidade. A diferença de atividade cortical das bandas de frequência entre as sessões sugere que o biofeedback modula a cognição por meio do esforço e atenção imposta pela tarefa na tentativa do movimento no membro acometido. Além de que a diferença de energia espectral entre as sessões é dependente do ajuste e complexidade da tarefa direcionado pelos sinais do biofeedback, auxiliando na aprendizagem motora. / Spasticity is observed in most patients after cerebrovascular accident (CVA), and exerts influence in the presence of disabilities, affecting motor function. For neurorehabilitation strategies, electromyographic biofeedback (EMG) has been used with acceptance in the medical community for adjustments in the sensory-motor skills as a motor retraining, reducing spasticity and/or relaxation training. The intervention still presents limited evidence regarding their effectiveness in rehabilitation, especially as the interference of cortical activity and the reduction of spastic signs that provides negative characteristics in movement execution. The aim of this study was to analyze the workout possible interference with EMG biofeedback on the motor control awareness in spastic member in the characterization of the activity of low-frequency bands in different cortical regions targeted by the training technique. Sixteen volunteers affected by ischemic stroke were selected and divided into two groups (n = 8). Experimental group (EG) underwent biofeedback training associated with physical therapy and control group (CG) only conventional physiotherapy. The assessment of the degree of spasticity by reflex threshold of the tonic stretch (TSRT) and Modified Ashworth Scale (MAS) was performed before and three weeks after the end of treatment with the technique. The subjects underwent biofeedback for 6 weeks, with two sessions weekly. The same time for physiotherapy treatment was standardized to the GC. The results show variation of the average percent improvement in the degree of spasticity measured at TRST, 38,59% (sd=13,03%) in GE compared to 18,58% (sd=11,90%) of GC. This variation showed a significant difference (p=0.020; t=2,776; p<5%) between groups (control and experimental), and the significant difference of TRST before and after training in EG (p = 0.003; t=5,338; p <5%) when compared to the CG (p=0.015; t=0,015; p<5%). The semi-quantitative measure of the MAS before and after the end of the sessions presented variations only in GE. Regarding the cortical activity, there were band activities differences when 3rd and 12th sessions were compared for each subject of GE. This difference was found primarily in the frontal, central (vertex), parietal and occipital lobe in both hemispheres (contralateral and ipsilateral to the lesion) in both the cognitive motor planning phase and in the movement execution. It was observed the predominance of activity difference for the delta band, alpha and beta in different subjects distributed diffusely over the EEG recording channels. The different activity of the bands was due to the increase and/or decrease the spectral energy between sessions, x noticed only in some GE volunteers. It was also pointed out distinct activity in secondary motor areas. Evaluations mainly from TSRT show that training with EMG biofeedback was effective in reducing the degree of spasticity. The difference in cortical activity of the frequency bands between sessions suggested that biofeedback modulates cognition through the effort and attention required by the task of movement attempt in the affected limb. Besides that, the spectral energy difference between the sessions depends on the tuning and task complexity driven by biofeedback signals, helping motor learning. / Tese (Doutorado)

Le système cholinergique est impliqué dans les phénomènes d’attention, de mémoire et d’apprentissage et les récepteurs cholinergiques régulent de multiples fonctions du système nerveux central. Néanmoins, leur rôle au niveau de la modulation des propriétés du cortex visuel reste à être établi. L’un des objectifs de cette thèse était d’étudier le rôle des récepteurs muscariniques impliqués dans le fonctionnement normal du cortex visuel. Nous avons pu déterminer que les récepteurs muscariniques sont impliqués dans l’établissement de nombreuses propriétés visuelles telles la taille des champs récepteurs, la sensibilité au contraste, la sélectivité à la fréquence spatiale et la finesse de la connectivité corticale. L’autre objectif était d’identifier les récepteurs cholinergiques impliqués dans la potentiation des capacités visuelles. Nous avons amélioré le traitement cognitif de l’information visuelle par stimulation électrique du télencéphale basal (noyau où sont localisés les corps cellulaires cholinergiques) et par la stimulation cholinergique par le donépézil, un inhibiteur de l’acétylcholinestérase. La combinaison répétée d’une stimulation visuelle et cholinergique (qu’elle soit électrique ou pharmacologique) améliore similairement l’activité corticale visuelle. Toutefois, les récepteurs impliqués ne sont pas les mêmes. Suite à la stimulation pharmacologique, ce sont principalement les récepteurs muscariniques qui influencent l’acuité visuelle de manière tardive et cette modulation est plus précoce lors de la stimulation électrique. Ces résultats démontrent que le couplage répétitif d’une stimulation cholinergique et d’une stimulation visuelle est en mesure d’améliorer l’activité corticale visuelle. Le fait de connaître les récepteurs cholinergiques impliqués permettra dans un futur proche de les cibler directement pour améliorer la fonction corticale. / The cholinergic system is involved in attention, learning and memory and cholinergic receptors regulate multiple functions of the central nervous system. Nevertheless, their role in modulating the properties of the visual cortex remains to be established. One of the objectives of this thesis was to study the role of muscarinic receptors involved in the normal function of the visual cortex. We have been able to determine that the muscarinic receptors are involved in the establishment of many visual properties such as the size of the receptor fields, contrast sensitivity, spatial frequency selectivity and accuracy of the cortical connectivity. The other objective was to identify the cholinergic receptors involved in the potentiation of visual abilities. We improved the cognitive processing of visual information by electrical stimulation of the basal forebrain (the nucleus where the cholinergic cell bodies are located) and by cholinergic stimulation using donepezil, an acetylcholinesterase inhibitor. The repeated combination of visual and cholinergic stimulations (whether electrical or pharmacological) similarly enhances visual cortical activity. However, the receptors involved are not the same. Following the pharmacological stimulation, it is mainly the muscarinic receptors that influence visual acuity with a delay in the receptors expression and this modulation is earlier for the electrical stimulation. These results demonstrate that repetitive coupling of cholinergic stimulation and visual stimulation can enhance visual cortical activity. Knowing the cholinergic receptors involved will allow in a near future to target them directly to improve cortical function.