Spike timing-dependent plasticity (STDP) has been suggested as one of the key mechanism underlying learning and memory. Due to its importance, timing-dependent plasticity studies have been approached in the living human brain by means of non-invasive brain stimulation (NIBS) protocols such as paired associative stimulation (PAS). However, contrary to STDP studies at a cellular level, functional plasticity induction in the human brain implies the interaction among target cortical networks and investigates plasticity mechanisms at a systems level. This thesis comprises of two independent studies that aim at understanding the importance of considering broad cortical networks when predicting the outcome of timing-dependent associative plasticity induction in the human brain. In the first study we developed a new protocol (ipsilateral PAS (ipsiPAS)) that required timing- and regional-specific information transfer across hemispheres for the induction of timing-dependent plasticity within M1 (see chapter 3). In the second study, we tested the influence of individual brain structure, as measured with voxel-based cortical thickness, on a standard PAS protocol (see chapter 4). In summary, we observed that the near-synchronous associativity taking place within M1 is not the only determinant influencing the outcome of PAS protocols. Rather, the online interaction of the cortical networks integrating information during a PAS intervention determines the outcome of the pairing of inputs in M1.

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Alcohol use disorder (AUD) is characterized by excessive habitual drinking and loss of control over alcohol intake despite negative consequences. Both of these aspects foster uncontrolled drinking and high relapse rates in AUD patients. Yet, common interventions mostly focus on the phenomenological level, and prioritize the reduction of craving and withdrawal symptoms. Our review provides a mechanistic understanding of AUD and suggests alternative therapeutic approaches targeting the mechanisms underlying dysfunctional alcohol-related behaviours. Specifically, we explain how repeated drinking fosters the development of rigid drinking habits and is associated with diminished cognitive control. These behavioural and cognitive effects are then functionally related to the neurobiochemical effects of alcohol abuse. We further explain how alterations in fronto-striatal network activity may constitute the neurobiological correlates of these alcohol-related dysfunctions. Finally, we discuss limitations in current pharmacological AUD therapies and suggest non-invasive brain stimulation (like TMS and tDCS interventions) as a potential addition/alternative for modulating the activation of both cortical and subcortical areas to help re-establish the functional balance between controlled and automatic behaviour.

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L’exposition aux impacts commotionnels et sous-commotionnels est une préoccupation majeure dans les sports de contact en raison de leurs effets néfastes sur la santé cérébrale. Des changements physiopathologiques et neurocognitifs ont été constatés après une seule saison de football chez des athlètes exposés à des coups sous-commotionnels. Vu l'absence d'outils sur les lignes de côtés permettant d'identifier les coups sous-commotionnels potentiellement dangereux, il est crucial de mettre au point des mesures objectives pour évaluer les perturbations neuropsychologiques aiguës associées aux chocs à la tête dans les sports de contact. Cette étude a pour but de documenter l'association entre l'exposition aux impacts à la tête pendant un match de football universitaire et les changements à court terme de l’excitabilité du cortex moteur primaire (M1) à l'aide de la stimulation magnétique transcrânienne (SMT). À cette fin, vingt-neuf athlètes masculins de niveau universitaire ont porté des protège-dents instrumentés (iMG) pendant un match de football afin de mesurer l'exposition aux impacts à la tête. Les mesures SMT ont été effectuées 24 heures avant et 1 à 2 heures après le match. De plus, vingt athlètes de football assigné au groupe contrôle ont participé à une séance d'entraînement physique sans contact et ont effectué les mêmes mesures de SMT. Les résultats suggèrent que, par rapport au groupe contrôle, le groupe d'athlètes ayant joué un match de football présentait une désinhibition intracorticale significative (p=0,028) sur l'inhibition intracorticale à intervalle court (SICI 3-ms) après le match. Par ailleurs, les joueurs de football exposés à un plus grand nombre de coups de 40g+ et à des forces cumulées plus importantes dues à des chocs de 40g+ présentaient une désinhibition intracorticale plus importante après le match. Compte tenu les effets délétères d'une diminution de l'inhibition sur le contrôle moteur et l'équilibre, suivre de manière systématique l'exposition aux impacts à la tête des athlètes tout au long de la saison pourrait s'avérer avantageux pour la gestion clinique des risques de blessure. Ces changements observés renforcent la conviction qu’il est nécessaire d’investiguer davantage les effets à long terme de l’exposition aux impacts sous-commotionnels. / Repetitive head impacts and sport-related concussions are significant concerns in contact sports due to their adverse effects on brain health. Pathophysiological and neurocognitive changes have been found after a single season of football in athletes exposed to subconcussive hits. Considering the lack of sideline tools to identify potentially dangerous subconcussive hits, coming up with objective measures to evaluate acute neurologic impairments associated with head impacts in contact sports is crucial from a clinical standpoint. The current project aimed to investigate the association between head impact exposure (HIE) during a varsity football game and short-term changes in cortical excitability of the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). To this end, we conducted a study, in which twenty-nine university-level male athletes wore instrumented mouthguards (iMGs) during a football game to measure HIE. TMS measurements were conducted 24 hours before and 1-2 hours after the game. Additionally, twenty control football athletes submitted to a non-contact physical training session and underwent identical TMS assessments. Results suggest that relative to controls, the group of athletes who had played a full contact football game exhibited a significant intracortical disinhibition (p=.028) on short-interval intracortical inhibition (SICI 3-ms) within hours following the game. Moreover, football players exposed to more 40g+ hits and greater cumulative forces from 40g+ head impacts exhibited greater post-game SICI disinhibition. Given the deleterious effects of decreased inhibition on motor control and balance, systematically tracking head impact forces throughout the course of contact sport season could reveal essential for sideline clinical management of head injury risk. These observed changes add to the concern that more research into the lasting consequences of HIE is needed.

In this report, we evaluate the role of visual areas responsive to motion in the human brain in the perception of stimulus speed. We first identified and localized V1, V3A, and V5/MT+ in individual participants on the basis of blood oxygenation level-dependent responses obtained in retinotopic mapping experiments and responses to moving gratings. Repetitive transcranial magnetic stimulation (rTMS) was then used to disrupt the normal functioning of the previously localized visual areas in each participant. During the rTMS application, participants were required to perform delayed discrimination of the speed of drifting or spatial frequency of static gratings. The application of rTMS to areas V5/MT and V3A induced a subjective slowing of visual stimuli and (often) caused increases in speed discrimination thresholds. Deficits in spatial frequency discrimination were not observed for applications of rTMS to V3A or V5/MT+. The induced deficits in speed perception were also specific to the cortical site of TMS delivery. The application of TMS to regions of the cortex adjacent to V5/MT and V3A, as well as to area V1, produced no deficits in speed perception. These results suggest that, in addition to area V5/MT+, V3A plays an important role in a cortical network that underpins the perception of stimulus speed in the human brain.

Les patients atteints de maladie de Parkinson présentent des troubles de la marche, parfois paroxystiques, pouvant être aggravés ou améliorés par les stimuli environnementaux. L'attention portée, soit aux stimuli extérieurs, soit à la marche, pourrait ainsi moduler la locomotion.L’objectif principal était donc de mieux caractériser la manière dont les stimuli environnementaux modulent par le biais de réseaux attentionnels la locomotion. Ceci a été étudié chez les sujets sains puis chez les patients parkinsoniens, avec ou sans enrayage cinétique.Nous avons d'abord défini précisément les déficits attentionnels des patients, avec ou sans troubles de la marche. Ils présentaient respectivement des difficultés en flexibilité mentale et plus particulièrement en attention divisée.Nous avons ensuite exploré l'interaction attention-locomotion grâce à l'étude de la préparation motrice. Ainsi, nous avons pu démontrer que les ajustements posturaux anticipés étaient un marqueur sensible de l’attention. Chez les patients, ils pouvaient témoigner d’une altération de l'interaction attention-programmation motrice.L'étude des régions cérébrales activées lors de la locomotion visuo-guidée chez ces patients a permis de confirmer l'implication de structures corticales attentionnelles. Un déséquilibre d’activation au sein du réseau pariéto-prémoteur (nécessaire à la modulation de l'action motrice en fonction des stimuli externes) était présent.Enfin, nous avons essayé de modifier l'excitabilité du cortex prémoteur via des techniques de stimulation magnétique transcrânienne répétitive afin de moduler la locomotion visuo-guidée. / Patients with Parkinson 's disease present gait impairments, sometimes sudden and unexpected, either improved or deteriorated with environmental stimuli. Attention focalization, either on external stimuli or on gait, could then modulate locomotion.The main objective was to better characterize how environmental stimuli would modulate locomotion, via attentional networks, in healthy subjects and in parkinsonian patients, with or without freezing of gait.At first, we precisely defined the attentional deficits in patients, with or without gait impairment. They showed altered performance respectively in mental flexibility and in divided attention.Then, we explored the attention-locomotion interaction by studying motor preparation. So, we highlighted that anticipatory postural adjustments were a sensitive marker of attention. In patients, they evidenced an alteration of the attention-motor program interaction.Studying the brain activation during the visuo-driven locomotion in these patients confirmed the involvement of cortical attentional regions. We observed an imbalance inside the parieto-premotor network (useful to modulate motor action according external stimuli)Finally, we tried to change the excitability of the premotor cortex with transcranial magnetic stimulation to modulate visuo-driven locomotion.