This doctoral thesis aimed at better understanding the contribution of sleep, Targeted Memory Reactivation and transcranial Direct Current Stimulation (tDCS) on the consolidation of neutral and emotional memories. In the first part of this work, we found that REM-enriched naps and more specifically rapid eye movement density is associated with the consolidation of sad stories, suggesting a possible implication of Ponto-Geniculo-Occipital (PGO) waves in the consolidation of sad information. In addition, we observed an increase in emotional reactivity during re-exposure to the sad story following a REM-enriched nap. We postulate that REM sleep favored the consolidation of the emotionalsalience of the sad memories, leading to exacerbated emotional reactivity during re-exposure. We also investigated the impact of TMR during NREM sleep on the consolidation of neutral and negative word pairs leanred with a specific sound. We found an equal benefit of the TMR procedure on neutral and emotional material, suggesting that emotion does not modulate the selective enhancing effect of TMR during NREM sleep. In an additional study, we tested the impact of verbatim presentation of the pairs of words during NREM sleep and did not find the memory benefits of TMR. We ascribed the absence of TMR memory benefit to the detrimental effect of the auditory presntation of the second word which impaired the memory reactivation processes initiated by the presentation of the first word. Together, theseresults indicate the crucial role of a sensitive plastic time window necessary for the successful processes of memory reactivation during sleep. Finally, we evaluated how the combination of tDCS and TMR procedure during a wakeful rest consolidation interval benefits memory consolidation. We found that TMR alone led to selective memory benefits for cued word pairs. When the TMR procedure was combined with either right-anodal or left anodal tDCS, we observed a significant improved global learning, suggesting that tDCS does not potentiate but overshadows the TMRprocedure. Altogether, these studies offer new perspectives in the field of memory consolidation. More specifically, the application of an alternating current during post-learning sleep concomitantly to a TMR procedure might favor the specific brain oscillations involved in successful memory reactivation, and might enhance the associated memory gains. / Doctorat en Sciences psychologiques et de l'éducation / info:eu-repo/semantics/nonPublished

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Objectif: Cette thèse vise à étudier si l’inhibition de la douleur par l’activation de la mémoire de travail (MT) peut être rehaussée par la Stimulation Transcranienne à Courant Direct (tDCS) chez des volontaires jeunes et des personnes âgées en bonne santé. La MT permet de sélectionner l’information pertinente à une tâche et de diriger l’attention vers l’exécution de cette tâche, permettant ainsi de limiter la capture de l'attention par des distracteurs, incluant la douleur. Cependant, cette inhibition de la capture attentionnelle par la douleur puisqu’il s’agit d’un processus descendant (top-down), peut être diminuée chez les personnes âgées en raison de la réduction des capacités de la MT. La tDCS est une méthode prometteuse à cet égard puisque la stimulation anodale du cortex préfrontal dorsolatéral (DLPFC) gauche permet d’améliorer les capacités de la MT. Méthodes: Cette thèse comporte deux expériences menées sur quarante jeunes adultes (première étude) et quinze personnes âgées (deuxième étude). Les expériences comportent deux séances de tDCS (tDCS anodale et simulée), pendant lesquelles de la douleur et le réflexe nociceptif de flexion étaient évoqués par une stimulation électrique à la cheville, alors que les participants exécutaient une tâche n-back (0-back et 2-back). Le protocole expérimental comportait cinq conditions dont l'ordre a été contrebalancé (0-back, 2- back, douleur, 0-back avec douleur et 2-back avec douleur), et qui ont été réalisées deux fois chacune (avant tDCS et pendant tDCS). Résultats: Les résultats indiquent que la neuromodulation du DLPFC gauche permet d’améliorer l’inhibition de la douleur par la MT, autant chez les jeunes adultes que chez les personnes âgées. Cependant, le réflexe nociceptif de flexion n’a pas été modulé par l’activation de la MT, suggérant que les effets bénéfiques de la tDCS reposent sur des mécanismes supraspinaux indépendants des voies inhibitrices descendantes. Ces études ont permis l'avancement des connaissances sur les interactions entre la cognition, la douleur et l'âge et montrent comment la neuromodulation peut changer ces interactions pour améliorer l'inhibition de la douleur. Ces résultats permettront le développement de protocoles de neuromodulation pour la gestion de la douleur chez les personnes âgées. / Objective: This thesis aimed to examine whether pain inhibition by working memory (WM) engagement can be enhanced by Transcranial Direct Current Stimulation (tDCS) in young and older healthy volunteers. Directing attention away from painful stimuli is under the control of WM that allows the selection of task-relevant information and directing attention towards task execution. However, top-down inhibition of nociceptive activity and pain may be altered in normal aging due to decreased WM. tDCS is a promising method in this regard since anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) was shown to improve WM performance. Methods: Two experiments were conducted on forty healthy (first study) and fifteen older volunteers (second study). They participated in two tDCS sessions (sham and anodal tDCS), in which the pain was evoked by electrical stimulation at the ankle. Participants performed an n-back task (0-back and 2-back) while they received random electrical stimulation to produce pain and the nociceptive flexion reflex, an index of spinal nociception. The experimental protocol comprised five counterbalanced conditions (0-back, 2-back, pain, 0-back with pain and 2-back with pain) that were performed twice (pre-tDCS baseline and during tDCS). Results: In both studies, neuromodulation of left DLPFC enhanced pain inhibition by WM. However, the nociceptive flexion reflex was not modulated by WM enhancement suggesting that improvement of pain inhibition by WM using tDCS is supraspinal and independent of descending inhibitory pathways. These studies improve our understanding of the interactions between cognition, pain and age and show how neuromodulation may change these interactions to improve pain inhibition. Findings support the development of neuromodulation protocols for pain management in older persons.

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Die Alkoholsucht ist ein global verbreitetes Phänomen und kennzeichnet sich durch eine Transition von kontrolliertem zu zwanghaftem Alkoholkonsum.Die Tendenz, einem neutralen Reiz eine Anreizwirkung zuzuschreiben, ist individuell unterschiedlich und stellt einen Risikofaktor für die Entwicklung einer Abhängigkeit dar.Zur Entwicklung spezifischer Präventionsstrategien ist ein besseres Verständnis der Zusammenhänge zwischen der Anreizsalienz und Alkoholabhängigkeit erforderlich.Der Übergang von mäßigem zu zwanghaftem Alkoholkonsum wurde durch das Modell des Alkoholentzugseffekts simuliert, das den menschlichen Alkoholrückfall nachahmt.Die Ratten erhielten freiwilligen Zugang zu verschieden Alkohollösungen mit wiederholten Deprivations- und Alkoholphasen.Die Ratten durchliefen zusätzlich den Pavlovian Conditioned Approach getestet, welcher die individuellen Tendenzen auf einen bedingten Reiz/Belohnung quantifiziert.Während des letzten ADE-Zyklus wurde mit Geschmacksverfälschung zwanghaftes Trinken ermittelt.Nach der Identifizierung zuverlässiger Prädiktoren für Suchtverhalten wurde präventive Neurostimulation durchgeführt, um die Tendenz der Tiere alkoholbezogenen Reizen eine motivationale Bedeutung beizumessen, zu beeinflussen, und die Manifestation eines Abhängigkeitsverhaltens zu verhindern. Weibchen tranken mehr Alkohol als Männchen und zeigten ST Verhalten im PavCA, während Männchen GT aufwiesen.Die Anwendung von transkranieller Gleichstromstimulation während PavCA führte zu mehr GT-Verhalten bei stimulierten Ratten.Frühe tDCS während des Trinkens hatte keinen Einfluss auf das akute und das Langzeit-Trinken. Die Ergebnisse zeigen eine komplexere Beziehung zwischen Anreizsalienz und Alkoholsucht und unterstreichen,individuelle Unterschiede und beide Geschlechter in der präklinischen Forschung zu berücksichtigen. / The consequences of alcohol dependence cause the global deaths of million people yearly.The ability of the environment can trigger dependent behavior and promote drinking.The tendency to attribute incentive salience to cues differs between subjects.By forming a cue-alcohol association, neutral cues receive motivational value,thereby predicting the likelihood of alcohol reward occurrence,known as Pavlovian learning.Understanding the relationship between incentive salience and alcohol addiction help inform treatment strategies.We study the relationship between incentive salience and alcohol addiction.The transition from moderate to compulsive alcohol intake can be captured by the alcohol deprivation effect rat model (mimics alcohol relapse in humans).Rats were given voluntary access to alcohol solutions with repeated abstinence/reintroduction phases.Further,rats were tested in the PavCA,which quantifies individual tendency toward a conditional cue and the reward, thus allowing to trace the process of attributing incentive salience to rewardcues.During the final ADE cycle,rats underwent a bitter taste adulteration test to assess for compulsive-like behavior.After identifying reliable predictors of addictive behavior,preventive tDCS was performed to influence the tendency of animals to attach motivational importance to alcohol-related stimuli,and to prevent the manifestation of alcohol addictive behavior.Females drank more alcohol than males and exhibited more ST behavior in the PavCA, whereas males showed GT behavior.PavCA phenotypes emerged early and remained stable.The application of tDCS during PavCA results in high GT numbers in stimulated rats.Early tDCS on drinking does not affect acute or long-term drinking.Our findings indicate a complex relationship between incentive salience and alcohol addiction and emphasize the importance of considering individual differences and both sexes in preclinical research.

Damage to the nervous system may cause sensorimotor impairment, often resulting in chronic neuropathic pain. Phantom limb pain affects multiple amputees and the treatment options are limited. A promising treatment option to reduce chronic pain is by training sensory discrimination. At the Center for Bionics and Pain Research, a sensory training device has been developed. Transcranial direct current stimulation (tDCS) is a technique to stimulate different regions of the cerebral cortex. In studies, anodal tDCS of the sensorimotor cortex has shown to improve tactile acuity. Until now, the effect of the sensory discrimination training, performed with the sensory training device, in combination with tDCS has not been tested. The purpose of this master’s thesis was to determine the effect of tDCS applied on the sensorimotor cortex on the outcomes of sensory discrimination training. The purpose was also to compare the effect of two different methods of stimulation, namely conventional and High Definition tDCS. 16 able-bodied participants underwent three single sessions with 40 minutes of sensory discrimination training: one session combined with conventional tDCS, one session combined with High Definition tDCS and one session without tDCS. The tactile acuity was determined by the two-point discrimination test and the Semmes-Weinstein monofilament test, prior to and one hour after each session. This study showed that 40 minutes of sensory discrimination training was sufficient to improve the two-point discrimination in the sensory trained areas, compared to the sensory untrained areas (p=0.02). However, the improvement in two-point discrimination was not statistically significant between the interventions, i.e. the improvement in two-point discrimination for the sessions with brain modulation was not statistically significant compared to the session without brain modulation. The monofilament assessments showed an improvement in monofilament score for the sensory untrained skin patches (p=0.053). This study concluded that single sessions of training was enough to improve two-point discrimination but not monofilament score at the site of stimulation. This study lays a foundation for what parameters to include in future studies.

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Le traitement visuel répété d’un visage inconnu entraîne une suppression de l’activité neuronale dans les régions préférentielles aux visages du cortex occipito-temporal. Cette «suppression neuronale» (SN) est un mécanisme primitif hautement impliqué dans l’apprentissage de visages, pouvant être détecté par une réduction de l’amplitude de la composante N170, un potentiel relié à l’événement (PRE), au-dessus du cortex occipito-temporal. Le cortex préfrontal dorsolatéral (CPDL) influence le traitement et l’encodage visuel, mais sa contribution à la SN de la N170 demeure inconnue. Nous avons utilisé la stimulation électrique transcrânienne à courant direct (SETCD) pour moduler l’excitabilité corticale du CPDL de 14 adultes sains lors de l’apprentissage de visages inconnus. Trois conditions de stimulation étaient utilisées: inhibition à droite, excitation à droite et placebo. Pendant l’apprentissage, l’EEG était enregistré afin d’évaluer la SN de la P100, la N170 et la P300. Trois jours suivant l’apprentissage, une tâche de reconnaissance était administrée où les performances en pourcentage de bonnes réponses et temps de réaction (TR) étaient enregistrées. Les résultats indiquent que la condition d’excitation à droite a facilité la SN de la N170 et a augmentée l’amplitude de la P300, entraînant une reconnaissance des visages plus rapide à long-terme. À l’inverse, la condition d’inhibition à droite a causé une augmentation de l’amplitude de la N170 et des TR plus lents, sans affecter la P300. Ces résultats sont les premiers à démontrer que la modulation d’excitabilité du CPDL puisse influencer l’encodage visuel de visages inconnus, soulignant l’importance du CPDL dans les mécanismes d’apprentissage de base. / Repeated visual processing of an unfamiliar face suppresses neural activity in face-specific areas of the occipito-temporal cortex. This "repetition suppression" (RS) is a primitive mechanism involved in learning of unfamiliar faces, which can be detected through amplitude reduction of the N170 event-related potential (ERP). The dorsolateral prefrontal cortex (DLPFC) exerts top-down influence on early visual processing. However, its contribution to N170 RS and learning of unfamiliar faces remains unclear. Transcranial direct current stimulation (tDCS) transiently increases or decreases cortical excitability, as a function of polarity. We hypothesized that DLPFC excitability modulation by tDCS would cause polarity-dependent modulations of N170 RS during encoding of unfamiliar faces. tDCS-induced N170 RS enhancement would improve long-term recognition reaction time (RT) and/or accuracy rates, whereas N170 RS impairment would compromise recognition ability. Participants underwent three tDCS conditions in random order at ~72 hour intervals: right anodal/left cathodal, right cathodal/left anodal and sham. Immediately following tDCS conditions, an EEG was recorded during encoding of unfamiliar faces for assessment of P100 and N170 visual ERPs. P300 was analyzed to detect prefrontal function modulation. Recognition tasks were administered ~72 hours following encoding. Results indicate the right anodal/left cathodal condition facilitated N170 RS and induced larger P300 amplitudes, leading to faster recognition RT. Conversely, the right cathodal/left anodal condition caused increases in N170 amplitudes and RT, but did not affect P300. These data are the first to demonstrate that DLPFC excitability modulation can influence early visual encoding of unfamiliar faces, highlighting the importance of DLPFC in basic learning mechanisms.

La stimulation électrique transcrânienne à courant direct (tDCS) est une technique non invasive de neuromodulation qui modifie l’excitabilité corticale via deux grosses électrodes de surface. Les effets dépendent de la polarité du courant, anodique = augmentation de l’excitabilité corticale et cathodique = diminution. Chez l’humain, il n’existe pas de consensus sur des effets de la tDCS appliquée au cortex somatosensoriel primaire (S1) sur la perception somesthésique. Nous avons étudié la perception vibrotactile (20 Hz, amplitudes variées) sur le majeur avant, pendant et après la tDCS appliquée au S1 controlatéral (anodale, a; cathodale, c; sham, s). Notre hypothèse « shift-gain » a prédit une diminution des seuils de détection et de discrimination pour la tDCS-a (déplacement vers la gauche de la courbe stimulus-réponse et une augmentation de sa pente). On attendait les effets opposés avec la tDCS-c, soit une augmentation des seuils (déplacement à droite et diminution de la pente). Chez la majorité des participants, des diminutions des seuils ont été observées pendant et immédiatement suivant la tDCS-a (1 mA, 20 min) en comparaison à la stimulation sham. Les effets n’étaient plus présents 30 min plus tard. Une diminution du seuil de discrimination a également été observée pendant, mais non après la tDCS-c (aucun effet pour détection). Nos résultats supportent notre hypothèse, uniquement pour la tDCS-a. Une suite logique serait d’étudier si des séances répétées de tDCS-a mènent à des améliorations durables sur la perception tactile. Ceci serait bénéfique pour la réadaptation sensorielle (ex. suite à un accident vasculaire cérébral). / Transcranial direct-current stimulation (tDCS) is a non-invasive neuromodulation technique which aims to modify cortical excitability using large surface-area electrodes. tDCS is thought to increase (anodal, a-tDCS) or decrease (cathodal, c-tDCS) cortical excitability. At present, there is no consensus as to whether tDCS to primary somatosensory cortex (S1) modifies somatosensory perception. This study examined vibrotactile perception (frequency, 20 Hz, various amplitude) on the middle finger before, during and after contralateral S1 tDCS (a-, c- and sham, s-). The experiments tested our shift-gain hypothesis which predicted that a-tDCS would decrease vibrotactile detection and discrimination thresholds (leftward shift of the stimulus-response function with increased gain/slope), while c-tDCS would increase thresholds (shift to right; decreased gain). The results showed that weak, a-tDCS (1 mA, 20 min), compared to sham, led to a reduction in both thresholds during the application of the stimulation in a majority of subjects. These effects persisted after the end of a-tDCS, but were absent 30 min later. Cathodal tDCS, vs sham, had no effect on detection thresholds; in contrast, there was a decrease in discrimination threshold during but not after c-tDCS. The results thus supported our hypothesis, but only for anodal stimulation. Our observation that enhanced vibrotactile perception outlasts, albeit briefly, the period of a-tDCS is encouraging. Future experiments should determine whether repeated sessions of a-tDCS can produce longer lasting improvements. If yes, clinical applications could be envisaged, e.g. to apply a-tDCS to S1 in conjunction with retraining of sensory function post-stroke.