Se déplacer selon un but déterminé est une activité courante de la vie quotidienne. Des capacités cognitives variées sont associées aux déplacements, comme la navigation, la mémoire ou encore l’orientation spatiale. De nombreux patients cérébro-lésés ou atteints par une maladie neuro-dégénérative présentent des difficultés topographiques qui retentissent sur leur autonomie en vie quotidienne. Les outils de réalité virtuelle permettent d’évaluer la navigation et la mémoire spatiale à grande échelle, avec une bonne corrélation entre cette évaluation et celle qui serait réalisée dans un environnement réel. La réalité virtuelle permet également d’ajouter des stimuli à la tâche proposée. Ces stimuli additionnels peuvent être contextuels, c’est à dire reliés à la tâche à réaliser dans l’environnement virtuel, ou noncontextuels, soit sans lien avec la tâche à accomplir. Ce travail de thèse s’est attaché à évaluer l’impact de stimuli auditifs et visuels sur la navigation et la mémoire spatiale de patients cérébro-lésés ou présentant une maladie neuro-dégénérative, dans des expériences de réalité virtuelle. Les deux premiers volets de cette thèse ont étudié l’effet de stimuli auditifs contextuels ou non-contextuels lors d’une tâche de courses au sein du supermarché virtuel VAP-S. Le premier volet a montré que des stimuli auditifs contextuels de type effet sonar et énoncé du nom du produit facilitaient la navigation spatiale de patients cérébro-lésés impliqués dans cette tâche de courses. Le second volet a mis en évidence que des sons non-contextuels avec une importante saillance cognitive ou perceptuelle péjoraient la performance de navigation de patients ayant présenté un accident vasculaire cérébral. Les deux volets suivants de cette thèse ont étudié l’effet d’indiçages visuels ou auditifs dans une tâche de navigation spatialedans un quartier virtuel. Ainsi, le troisième volet de la thèse a démontré que des indices visuels comme des flèches directionnelles ou des points de repère sursignifiés facilitaient la navigation spatiale et certains aspects de mémoire spatiale de patients avec des troubles cognitifs légers (MCI) ou présentant une Maladie d’Alzheimer. Enfin, le quatrième volet a mis en évidence qu’un indiçage auditif par des bips indiquant la direction à chaque intersection améliorait la navigation spatiale de patients cérébro-lésés droits présentant une héminégligence visuelle et auditive controlatérale. Ces résultats suggèrent que des stimuli auditifs et visuels pourraient être utilisés lors de prises en charge rééducatives et réadaptatives de patients présentant des difficultés topographiques, ainsi qu’en vie quotidienne par le biais de la réalité augmentée afin de faciliter leurs déplacements. L’impact des stimuli chez les sujets sains et chez les cérébrolésés est différent et justifie une analyse spécifique de processus probablement distincts impliqués lors des déficits cognitifs. / Navigating in a familiar or unfamiliar environment is a frequent challenge for human beings. Many patients with brain injury suffer from topographical difficulties, which influences their autonomy in daily life. Virtual Reality Tools enable the evaluation of largescale spatial navigation and spatial memory, resembling a real environment. Virtual reality also permits to add stimuli to the software. These stimuli can be contextual, that is to say linked to the task that participants have to accomplish in the Virtual Environment, or non-contextual, i.e. with no link with the require task. This thesis investigates whether visual or auditory stimuli influence spatial navigation and memory in Virtual Environments of patients with brain injury or with a neurodegenerative disease. The first part of the thesis showed contextual auditory stimuli type a sonar effect and the names of products of the shopping list improved spatial navigation of brain-injured patients during a shopping task in the virtual supermarket VAP-S. The second part of this thesis highlighted that non-contextual auditory stimuli with a high perceptual or cognitive salience decreased spatial navigation performance of brain-injured patients during a shopping task in the VAP-S. The third part of this thesis showed that visual cues like directional arrows and salient landmarks improved spatial navigation and some aspects of spatial memory of patients with Alzheimer’s disease or Mild Cognitive Impairments during a navigation task in a virtual district. The last part of this thesis demonstrated that auditory cues, i.e. beeping sounds indicating the directions, increased spatial navigation in a virtual district of patients who have had a stroke with contra-lesional visual and auditory neglect. These results suggest that some visual and auditory stimuli could be helpful for spatial navigation and memory tasks in patients with brain injury of neuro-degenerative disease. It further offers new research avenues for neuro-rehabilitation, such as the use of augmented reality in real-life settings to support the navigational capabilities of these patients.

La navigation spatiale désigne la capacité de s'orienter et se repérer dans un environnement, et est particulièrement altérée chez les personnes âgées. Dans ce travail de thèse, nous proposons d'identifier les mécanismes sous-tendant le déclin de cette fonction chez les seniors. Nous avons comparé les performances de participants âgés à celles de sujets jeunes lors de tâches spatiales, et employé la technique des potentiels évoqués (PE) afin d’analyser les mécanismes neuronaux sous-jacents. Nous avons montré une atteinte de la localisation allocentrique chez les seniors, tandis que la localisation égocentrique semble préservée. Nous avons étudié l'efficience de processus visuo-perceptifs et attentionnels chez les sujets âgés. L'analyse des PE montre une préservation des processus perceptifs avec l'âge, tandis que les processus d'attention spatiale semblent particulièrement décliner. Enfin, les processus d'encodage spatial semblent également affectés chez les sujets âgés. / Spatial navigation refers to the ability to find one's way in complex environments, and is particularly affected in elderly individuals. We aimed to better understand the mechanisms underlying age-related deficits in spatial navigation, focusing on early cognitive processes. For this purpose, we compared performances obtained by elderly individuals above 60 years and by younger adults during spatial tasks, and used the event-related potentials (ERP) technique to investigate underlying neural processes. First, we found that allocentric localization is impaired in aging, whereas egocentric localization seems to be preserved. Then, we investigated the role of visuo-perceptive or attentional processes in spatial cognition, and their preservation in aging. ERP showed that perceptive processes seem to be preserved in elderly individuals, whereas spatial attention processes were impaired in these subjects. Finally, we showed that encoding processes are also particularly affected by aging.

Spatial navigation is essential for survival not only in mammals. Neural and neuropharmacological changes of learning and memory in humans and rats could be measured through their behavior and responses to stimuli. In focus of experimental models of cognitive deficits, the Morris water maze (MWM) represents a clasiccal test of exact allothetic representation, i.e. the cognitive map. Another important test of spatial navigation is the active place avoidance, or Carousel maze (also AAPA, Active Allothetic Place Avoidance), that can be used to test the ability of cognitive coordination, thus the ability to distinguish relevant stimuli from irrelevant. There are analogous tasks for testing cognitive abilities in humans for both tests (e.g. Blue Velvet Arena for MWM, virtual reality simulations on PC for AAPA, etc.). Aim of the present study is to compare the sensitivity of outbred Long-Evans and Wistar strains of rats from the institutional breeding to the acute administration of scopolamine, the antagonist of central muscarinic acetylcholine receptors, at doses 0.8 mg/kg; 1.5 mg/kg and 3.0 mg/kg. The results show that the Wistar strain is more influenced by cholinergic blockade than Long-Evans strain in both AAPA and the MWM. Furthermore, it appears that the control rat strain Long-Evans have better...

Spatial navigation, cognitive coordination and behavioral flexibility belong amongst cognitive functions, which play a role in many neuropsychiatric disorders. Behavioral tasks have proved to be useful paradigms to test these functions in pharmacological or genetic animal models. First aim was to determine a potential interaction between β-adrenergic and α1-adrenergic or D2-dopaminergic systems. Spatial navigation and coordination were impaired in both studies during co-aplication of subthreshold doses of drugs. Used substances belong to group of widely prescribed drugs, thus our results could be implicated in clinical practice. Another study examined an acute effect of MK-801 (animal model of schizophrenia) on behavioral flexibility in Carousel maze and the Morris water maze (MWM). Carousel maze showed higher sensitivity with impairments from 0.08 mg.kg-1 compared to 0.10 mg.kg- 1 in MWM. The final experiment aimed at testing the effect of reduced expression of Nogo-A protein on spatial navigation and behavioral flexibility of rats. A battery of tests in the Carousel maze revealed impairment in cognitive functions, MWM showed unaffected working memory of rats. Our results support the hypothesis linking Nogo-A knock-down rats with neuropsychiatric symptoms and cognitive disorders. Key words:...

Spatial navigation, cognitive coordination and behavioral flexibility belong amongst cognitive functions, which play a role in many neuropsychiatric disorders. Behavioral tasks have proved to be useful paradigms to test these functions in pharmacological or genetic animal models. First aim was to determine a potential interaction between β-adrenergic and α1-adrenergic or D2-dopaminergic systems. Spatial navigation and coordination were impaired in both studies during co-aplication of subthreshold doses of drugs. Used substances belong to group of widely prescribed drugs, thus our results could be implicated in clinical practice. Another study examined an acute effect of MK-801 (animal model of schizophrenia) on behavioral flexibility in Carousel maze and the Morris water maze (MWM). Carousel maze showed higher sensitivity with impairments from 0.08 mg.kg-1 compared to 0.10 mg.kg- 1 in MWM. The final experiment aimed at testing the effect of reduced expression of Nogo-A protein on spatial navigation and behavioral flexibility of rats. A battery of tests in the Carousel maze revealed impairment in cognitive functions, MWM showed unaffected working memory of rats. Our results support the hypothesis linking Nogo-A knock-down rats with neuropsychiatric symptoms and cognitive disorders. Key words:...

As nomads, humanity constantly moved and relocated for hundred thousands of years. Thereby, individuals or small groups of people had to navigate over very long distances in order to survive. As a result, successful spatial navigation was one of the key cognitive abilities, which ensured our survival. Although navigation has nowadays become less life-threatening, exploring our environment and efficiently navigating between places are still very important aspects in our everyday life. However, in order to be able to navigate efficiently, our brain has to perform a series of spatial cognitive operations. This dissertation is structured into three sections, which explore these cognitive operations from three different perspectives. In the first section I will elaborate about the role of reference frames in human spatial navigation. Specifically, in an online navigation study (study one) I will show that humans have distinct but stable reference frame proclivities. Furthermore, this study demonstrates the existence of a spatial strategy, in which the preference to use a particular reference frame is dependent on the axis of rotation (horizontal vs. vertical). In a follow-up study (study two) I will then analyze the factors underlying performance differences in navigation, as well as individual preferences using one or another spatial strategy. Interestingly, the results suggest that performance measures (reaction time and error rate) are influenced mostly by the factors gender and age. However, even more importantly, I will show that the prevalent factor, which influences the choice for an individual navigation strategy, is the cultural background of the participant. This underlines the importance of socio-economic aspects in human spatial navigation. In the second part of this thesis I will then discuss aspects of learning and memorizing spatial information. In this respect, the alignment study (study three) will show that humans are able to recall object-to-object relations (e.g. how to get from A to B) in a very brief time, indicating that such information is directly stored in memory. This supports an embodied (action-oriented) perspective of human spatial cognition. Following this approach, in the feelSpace study (study four) I will then investigate the long-term training effects with a sensory augmentation device. Most importantly, the respective results will demonstrate substantial changes in the subjective perception of space, in sleep stage architecture, and in neural oscillations during sleep. In the third and last section I will describe the importance of multimodal processes in spatial cognitive operations. Most importantly, in the platform study (study five) I will combine the topics of sensory augmentation and Bayesian cue combination. The results of this study show that untrained adult participants alternate rather than integrate between augmented and native sensory information. Interestingly, this alternation is based on a subjective evaluation of cue reliability. In summary, this thesis will present relevant and new findings for better understanding spatial strategy formation, learning and representing spatial relations in memory, and multimodal cue combination. An important and overarching aspect of this thesis is the characterization of individual differences in the context of human spatial navigation. Specifically, my research revealed individual differences in three areas: First, in utilizing egocentric or allocentric reference frames for spatial updating, second in individualized qualitative changes of space perception during long-term sensory augmentation, and third, in preferences to use native or augmented information in a cue combination task. Most importantly, I will provide a better definition and understanding of these individual differences, by combining qualitative and quantitative measures and using latest technologies such as online data recordings and interactive experimental setups. In fact, in the real world, humans are very active beings who follow individualized spatial cognitive strategies. Studying such interactive and individualized behavior will ultimately lead to more coherent and meaningful insights within the human sciences.

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Disruption of cognitive abilities such as learning, memory and spatial navigation accompanies a number of neuropsychiatric disorders including schizophrenia. Cognitive symptoms are also most difficult to target by available pharmacotherapy.. Behavioral and molecular evidence point to a disruption of NMDA receptors and glutamatergic and dopaminergic neurotransmission. Impaired cognitive coordination has been proposed as a core cognitive deficit in schizophrenia. Non- competitive NMDAR antagonists are used to model schizophrenia- related symptoms in humans and in experimental animals. Place avoidance on a rotating arena is used to model cognitive functions disrupted in an animal model of schizophrenia. The goal of this thesis is to show whether the deficit in place avoidance is due to disrupted cognitive coordination or another effect of NMDAR antagonism such as hyperlocomotion, general learning deficit, or altered sensitivity.

Ces dernières années, la prise en compte des difficultés quotidiennes des personnes a largement évolué pour être aujourd’hui au centre des préoccupations des cliniciens et chercheurs. Dans le vieillissement en particulier, les difficultés quotidiennes tiennent une place particulière car elles constituent un critère de diagnostic de la démence mais également un facteur de risque de celle-ci, même en l’absence de trouble cognitif avéré.Leur prise en compte relève donc d’un intérêt majeur mais pose la question de leur mesure, notamment au vu des relations non systématiques qu’elles entretiennent avec les troubles cognitifs évalués par les tests neuropsychologiques traditionnels et les plaintes des sujets. Les approches écologiques, la réalité virtuelle en particulier, dans lesquelles s’inscrivent nos travaux, tentent de proposer une évaluation de la cognition « quotidienne » en espérant par ce bais, fournir des mesures qui soient à la fois précises, spécifiques et reflétant le fonctionnement quotidien de la personne. L’utilisation de deux environnements virtuels, représentant un appartement et un quartier résidentiel nous a permis de dégager des profils cognitifs spécifiques associés au vieillissement normal et à la maladie d’Alzheimer dans le cadre de la mémoire épisodique et de navigation spatiale. Ces profils sont discutés en référence au modèle multifactoriel du vieillissement et au regard de l’objectivation des difficultés quotidiennes des personnes. L’application de ces recherches pour le développement d’aides à l’autonomie des âgés est proposé comme perspective de travail. / These last years, taking account of everyday difficulties has largely improved and is at the core of preoccupations of clinicians and researchers.Particularly, everyday difficulties hold a special place in aging because of their potential value as a diagnostic criterion, but also as a risk factor, for dementia, even in the absence of cognitive impairment. However, despite being taken into consideration and their major interest, their assessment is being questioned, especially regarding their inconsistent relationships with cognitive impairments assessed by traditional neuropsychological tests and subjects’ complaints. The purpose of ecological approaches, particularly those using virtual reality technologies, in which our work is framed, is to assess the “daily” cognition, by which we hope providing measures that are accurate, specific and reflecting the one’s daily functioning. The use of two virtual environments, an apartment and a residential district, has allowed us identifying specific cognitive patterns of episodic memory and spatial navigation associated with normal aging and Alzheimer's disease. These patterns are discussed according to the multifactorial model of aging and the objective assessment of daily difficulties.The application of this research to the development of aids for the autonomy of the elderly is proposed as a work perspective.

La navigation est une fonction clé de l’évolution. Chez l’Humain, comme chez le Rat, elle repose sur au moins deux structures cérébrales : l’hippocampe et le striatum. Chacune de ces structures prend en charge un mode de navigation qui lui est propre, et qui dépend du degré de connaissance de l’environnement et de la monotonie de la tâche. A l’heure actuelle, on ne comprend pas bien comment l’hippocampe et le striatum interagissent lors du rappel d’une information spatiale. L’objectif de cette thèse a été de mieux caractériser ce dialogue hippocampo-striatal. A travers des inactivations temporaires, couplées à un entraînement progressif dans un test comportemental, j’ai pu montrer une interdépendance de ces deux structures lors du rappel d’une information spatiale après 6 jours d’entrainement. Cette relation évolue après 14 jours d’entrainement, où l’intégrité des deux structures n’est plus requise pour le rappel d’une stratégie allocentrée. / Spatial navigation is a key function of the evolution. In Human, as in Rat, it is based on at least two brain structures: the hippocampus and the striatum. Each of these structures supports a navigation mode of its own, which depends on the level of knowledge of the space environment and the monotony of the task. Currently, we don’t really understand how these two structures interact during retrieval of a spatial information. The aim of this thesis was to better characterize hippocampo-striatal dialogue during the implementation of a routine in the rat. Through muscimol inactivation, coupled to progressive period training in a behavioral test, I was able to show the interdependence of these two structures in the development of a relevant navigation strategy during retrieval after 6 training days. This relationship evolves after 14 days of training, where, hippocampus does not seem to depend on the integrity of dorsal striatum anymore to provide an allocentric strategy.