Mindfulness-based meditation practices involve various attentional skills including the ability to sustain and focus ones attention. During a simple mindfulness based breath awareness meditation, sustained attention is required to maintain focus on the breath while meta-cognitive awareness and executive control are required to detect and correct mind wandering. The purpose of this thesis was to investigate whether a simple, mindfulness based breath awareness meditation, administered over a short period to meditation naïve individuals could modulate core attentional functions and associated task related neural activity. Two longitudinal randomised control studies were conducted. The aim of the first study was to establish if said modulations were possible in a sample of healthy adults, meeting a current research need for longitudinal evidence in this field and providing important information regarding a potential mechanism for the salutary effects widely observed from the use of mindfulness based interventions. It was found that short term engagement with a mindfulness based breath awareness meditation can modulate core attentional functions and task related neural activity, with specific modulations found in electrophysiological markers of sustained attention to the goal/task at hand and perceptual stimulus discrimination. In line with current theoretical models it is argued that modulations to such core attentional processes following short term training may provide a platform upon which mindfulness related salutary effects are built. The second study was designed to establish if such modulations were possible in older adults. It is argued that mindfulness training may have utility for increasing cognitive reserve, a potential mechanism by which age related declines in cognitive functions may be mitigated. It was found that both behavioural and electrophysiological markers of core attentional functions were modulated following 8 weeks mindfulness training but not following a matched active control group condition (simple brain training exercises). The reviewed extant evidence and findings of this study suggest that mindfulness meditation may enhance cognitive reserve through the repeated activation of attentional functions and associated neural activity during practice and are consistent with recent theoretical models of cognitive reserve. The potential for mindfulness training to positively modulate core attentional functions in older adults and to potentially impact cognitive ageing demands further investigation.

Cognitive impairment is common in multiple sclerosis (MS), with as many as 70% of patients with MS affected. Individuals with MS who experience cognitive deficits are less likely to be employed, and may have more difficulty performing independent activities of daily living. Most commonly, deficits are observed in processing speed, complex attention, and memory. Because lesion location varies widely among individuals, no clear pattern of cognitive dysfunction in MS has emerged. However, a number of risk and protective factors may influence the likelihood of individuals to develop and/or express dysfunction, though the contribution of each to specific domains of cognition has not been fully explored. Recently, support for the cognitive reserve hypothesis (i.e., enriching life experiences protect against cognitive decline despite disease burden) has emerged in the MS literature. The current study investigated the contributions of cognitive reserve to learning and memory functioning in MS and the interaction of cognitive reserve variables and risk factors known to impact cognitive functioning in individuals with MS. Finding revealed cognitive reserve protects against decline in the domains of processing speed and complex attention. Furthermore, indirect protective effects of cognitive reserve through these domains were observed for verbal learning and memory. Finally, in line with previous literature, cognitive dysfunction predicted employment status of the current sample. Clinical implications and future directions for intervention efforts are discussed.

Lors du vieillissement sain, et malgré une augmentation de la fréquence d’apparition du manque du mot, les personnes âgées manifestent une préservation des performances de dénomination orale d’objets (DO), suggérant la mise en place de stratégies efficaces de récupération et de sélection de l’information lexicale. Dans ce travail de thèse, nous avons utilisé une approche méthodologique multimodale afin d’évaluer la nature de ces stratégies. Nous nous sommes plus spécifiquement intéressés aux mécanismes de réorganisation cérébrale ainsi qu’aux activités sociales comme facteur de réserve cognitive. Ce travail de thèse se décompose en cinq études et aborde une perspective homogène (effet de l’âge) et hétérogène (effet des performances) du vieillissement. Nos résultats mettent en évidence l’existence de différents mécanismes de compensation associés au vieillissement sain. Tout d’abord, nous observons que les personnes âgées sont plus lentes que les jeunes adultes lors de la DO, mais obtiennent un taux de précision similaire. D’après la perspective homogène, le maintien des performances de DO s’expliquerait par le recrutement d’une stratégie de nature sémantique. Au niveau cérébral, nous observons une augmentation de l’asymétrie intra-hémisphérique gauche des régions temporo-pariétales chez les personnes âgées, ainsi qu’un transfert de la connectivité normalement observée du gyrus frontal inférieur (GFI) gauche avec le gyrus temporal latéral au gyrus temporal médial gauche. D’après la perspective hétérogène, le maintien des performances de DO s’expliquerait par l’utilisation d’une stratégie de nature exécutive, reflétée par une réduction de l’asymétrie inter-hémisphérique frontale chez les personnes âgées dont les temps de réponse de DO sont courts. Par ailleurs, nous proposons que l’encodage lexico-phonologique module également le taux de précision de DO, via la connectivité effective entre le GFI gauche et le gyrus temporal supérieur gauche. Enfin, nous observons une relation significative entre la fréquence de participation aux activités sociales, notamment collectives, et les performances de DO. Cette relation est partiellement médiée au niveau cérébral par l’activité du gyrus frontal supérieur médian gauche, via un mécanisme de réserve neurale. Sur la base de nos résultats, nous proposons un modèle neurocognitif des stratégies de récupération et de sélection de l’information lexicale, utilisant une approche multimodale et plurifactorielle du vieillissement sain. / Despite increased difficulties to find words in the daily life, older adults show preserved object naming performances when compared to younger ones. This suggests a supplementary recruitment of compensatory strategies in order to retrieve and select words. In this research work, we have used a multimodal methodological approach to evaluate the nature of these strategies, by using an object naming task. Specifically, we have evaluated these strategies in terms of mechanisms of cerebral reorganization. We were also interested to know how these strategies are modulated by the frequency of social activities, considered as a factor of cognitive reserve. This thesis work is composed of five studies performed under a homogeneous (effect of age) and a heterogeneous (effect of performance) perspective. Based on results, we suggest that aging is associated with multiple compensatory mechanisms to maintain a correct level of performance. Specifically, according to the homogeneous perspective, we consider that preserved object naming performances in older adults might be explained by the use of a semantic strategy. Indeed, in older compared to younger adults and at a cerebral level, we observed increased left hemispheric asymmetry with significant recruitment of the temporo-parietal regions. In addition, the inferior frontal gyrus (IFG) that is connected to the lateral temporal cortex in younger adults, seems to “switch” its connectivity toward the left medial temporal gyrus in older adults. In addition, according to the heterogeneous perspective, preserved object naming performances in older adults can be also explained by the use of an executive strategy, reflected by reduced inter-hemispheric asymmetry of frontal regions, specifically in more performant older adults (with shorter response latencies). Furthermore, we suggest that lexico-phonological processes mediate naming accuracy as reflected by the increased connectivity from the left IFG to the left superior temporal gyrus. A final result that we report in this work indicates that the frequency of participation to group social activities correlates to naming performance in older adults. This relation is partially mediated by the left superior medial frontal gyrus and is assimilated to a neural reserve mechanism. Overall, based on our findings, we propose a neurocognitive model of lexical retrieval and selection strategies in normal aging, based on a multimodal dataset and a multifactorial approach.

Objectives: The purpose of this thesis is to explore the associations between childhood cognitive abilities assessed at age 8 and health and socioeconomic outcomes at age 29-36 in extremely low birth weight survivors (ELBW, <1000g). Methods: Using data from the McMaster Extremely Low Birth Weight Cohort Study, Study 1 explores the influence of overall intelligence, fluid intelligence, and language abilities on the prevalence of lifetime major depressive disorder in ELBW survivors and normal birth weight comparison subjects. Study 2 examines the mediating role of overall intelligence, fluid intelligence, language abilities, quantitative reasoning, and academic achievement on the association between being born at ELBW and socioeconomic outcomes at age 29-36. The final study examines the moderating role of childhood cognitive functioning on links between postnatal psychosocial adversity and adult personal earnings in ELBW survivors. Results: Results from Study 1 suggest that childhood cognitive abilities do not influence the onset of major depressive disorder in ELBW survivors, but are protective against depression in normal birth weight individuals. Study 2 suggests that childhood cognitive abilities partially mediate the association between being born at ELBW and income attainment in adulthood, but not full time employment. Further, Study 2 suggests that this association is stronger in ELBW survivors who have neurosensory impairments. Results of Study 3 suggest that enhanced childhood cognitive functioning is not protective against postnatal psychological adversity in influencing income attainment, as those ELBW survivors with higher childhood intelligence and who suffered psychological adversity reported lower annual income at age 30. Conclusions: This thesis suggests that overall and specific cognitive abilities significantly influence adult outcomes in ELBW survivors and normal birth weight individuals. However, while cognitive reserve may not be protective against psychological adversity in ELBW survivors, early cognitive abilities are a critical indicator of socioeconomic attainment in this vulnerable population. / Thesis / Master of Science (MSc) / The following thesis explores the predictive role of childhood cognitive abilities on adult health and socioeconomic outcomes in extremely low birth weight survivors at age 29-36. Study 1 explores the influence of overall intelligence, fluid intelligence, and language abilities assessed at age 8 on the prevalence of lifetime major depressive disorder in extremely low birth weight survivors and normal birth weight comparison participants. Study 2 examines the mediating role of overall intelligence, fluid intelligence, language abilities, quantitative reasoning, and academic achievement on the association between being born at extremely low birth weight and socioeconomic outcomes at age 29-36. The final study examines the moderating role of childhood cognition on the association between postnatal psychosocial adversity and personal income attainment at age 30 in extremely low birth weight survivors. Overall, this body of work suggests that childhood cognitive abilities are an important contributor to adult outcomes in preterm survivors.

Le vieillissement normal est associé à une réorganisation cérébrale qui peut être influencée par plusieurs facteurs. Des théories comme la réserve cognitive de Stern (2002) tentent d’expliquer les effets de ces différents facteurs. Certains, le niveau de scolarité par exemple, sont encore mal connus. Pourtant, le niveau de scolarité est connu pour avoir un impact sur les performances cognitives tout au long de la vie. Le but de ce mémoire est d’étudier les effets du niveau de scolarité sur l’oxygénation cérébrale de personnes âgées en santé lors d’une tâche d’évocation lexicale orthographique et sémantique. Chaque tâche est divisée selon un critère « plus productive » et « moins productive ». Les âgés faiblement scolarisés produisent moins de mots que les âgés fortement scolarisés. De plus, la différence de mots produits entre le critère plus productif et moins productif est plus grande pour la tâche sémantique que pour la tâche orthographique. Du point de vue hémodynamique, les deux groupes ont des activations semblables, contredisant le phénomène HAROLD. De plus, les participants peu scolarisés tendent à activer de façon plus importante l’hémisphère gauche, peu importe la tâche ou la condition. Par contre, les activations varient selon la tâche et la condition dans le cas du groupe fortement scolarisé. / Normal aging is associated with cerebral reorganisation which can be influenced by many factors. For example, the theory cognitive reserve (Stern, 2002) is trying to explain how those factors can have an impact on the reorganization. However, some factors, such as educational level, are known to have an impact on cognitive performance. The aim of this dissertation is to study the effect of educational level in cerebral oxygenation of healthy older adults during both phonologic and semantic verbal fluency tasks. Each task is divided into two criteria: more productive and less productive. Behavioural data showed that less educated elderly generate fewer words than more educated ones for both tasks. Moreover, the differences between the number of words for the more productive criterion and the less productive one are higher for the semantic than for the phonologic task. NIRS data showed that both groups activated prefrontal cortex, without difference between them. In addition, less educated participants tend to have bigger activations in the left hemisphere regardless of the task and the criterion. On the other hand, higher educated participants’ activations vary according to the task and the criterion unlike the HAROLD model’s predictions.

Le vieillissement normal est associé à une réorganisation cérébrale qui peut être influencée par plusieurs facteurs. Des théories comme la réserve cognitive de Stern (2002) tentent d’expliquer les effets de ces différents facteurs. Certains, le niveau de scolarité par exemple, sont encore mal connus. Pourtant, le niveau de scolarité est connu pour avoir un impact sur les performances cognitives tout au long de la vie. Le but de ce mémoire est d’étudier les effets du niveau de scolarité sur l’oxygénation cérébrale de personnes âgées en santé lors d’une tâche d’évocation lexicale orthographique et sémantique. Chaque tâche est divisée selon un critère « plus productive » et « moins productive ». Les âgés faiblement scolarisés produisent moins de mots que les âgés fortement scolarisés. De plus, la différence de mots produits entre le critère plus productif et moins productif est plus grande pour la tâche sémantique que pour la tâche orthographique. Du point de vue hémodynamique, les deux groupes ont des activations semblables, contredisant le phénomène HAROLD. De plus, les participants peu scolarisés tendent à activer de façon plus importante l’hémisphère gauche, peu importe la tâche ou la condition. Par contre, les activations varient selon la tâche et la condition dans le cas du groupe fortement scolarisé. / Normal aging is associated with cerebral reorganisation which can be influenced by many factors. For example, the theory cognitive reserve (Stern, 2002) is trying to explain how those factors can have an impact on the reorganization. However, some factors, such as educational level, are known to have an impact on cognitive performance. The aim of this dissertation is to study the effect of educational level in cerebral oxygenation of healthy older adults during both phonologic and semantic verbal fluency tasks. Each task is divided into two criteria: more productive and less productive. Behavioural data showed that less educated elderly generate fewer words than more educated ones for both tasks. Moreover, the differences between the number of words for the more productive criterion and the less productive one are higher for the semantic than for the phonologic task. NIRS data showed that both groups activated prefrontal cortex, without difference between them. In addition, less educated participants tend to have bigger activations in the left hemisphere regardless of the task and the criterion. On the other hand, higher educated participants’ activations vary according to the task and the criterion unlike the HAROLD model’s predictions.

Today, as we live longer, dementia diseases are becoming more prevalent around the world. Thus, further knowledge of how to maintain levels of cognitive functioning in old age and how to identify factors that postpone the onset of dementia are of acute interest. Lifestyle patterns and social life are important aspects to consider in this regard. This thesis includes three studies. Study I investigated the association between participation in various leisure activities in old age (≥65 years) and risk of incident all-cause dementia. Analyses of the total follow-up time period (15 years) showed that higher levels of “Social” and “Total” leisure activity were associated with decreased risk of dementia. In Study II, the aim was to investigate the association between various aspects of social relationships in old age (≥65 years) and risk of incidents of all-cause dementia and Alzheimer's disease. Results showed that over the total follow-up period (16 years) higher values on the relationship index were associated with reduced risk of both dementia and Alzheimer's disease. Visiting/visits of friends and acquaintances more than once a week was related to decreased risk for all-cause dementia, but not for Alzheimer's disease. However, in neither Study I nor II did any of these factors alter the risk of all-cause dementia or Alzheimer's disease when near-onset dementias were removed from the analyses (Study I, up to five years; Study II, up to three years). In Study III the aim was to investigate the association between social network size and cognitive ability in a middle-aged (40–60 years) sample. The idea was that if social network size can moderate negative age-related influence on memory functions, it might also put an individual on a cognitive trajectory that is beneficial in old age. Results from longitudinal analyses showed that baseline network size was positively related to five-year changes in semantic memory and with changes in both semantic and episodic memory at the ten-year follow-up. Social network size was unrelated to changes in visuospatial performance. Taken together, enrichment factors measured in old age (≥ 65 years) did not alter the risk of all-cause dementia or Alzheimer's disease when near-onset dementias were removed from the analyses. These results might reflect protective short-term effects or reverse causality, meaning that in the prodromal phase of dementia individuals tend to withdraw from activity. Social network size in middle age (40-60 years), however, appears to have beneficial long-term effects on cognitive functioning. The results highlight the importance of long follow-up periods and the need to adjust for the influences of reverse causality when investigating the impact of a socially and mentally active life on cognitive functioning.

Le vieillissement cérébral normal est caractérisé par un déclin progressif de la capacité de traitement des informations en particulier dans le système de la mémoire de travail. Il apparaît donc essentiel d'explorer l'organisation corticale cérébrale sous-jacente au mécanisme de la mémoire de travail dont l'évaluation est rendu possible par l'imagerie par résonance magnétique fonctionnelle (IRMf). Les objectifs de notre travail ont consisté à identifier, dans une large cohorte d'individus âgés en bonne santé, les réorganisations des réseaux neuronaux en relation avec (i) l'augmentation de la difficulté d'une tâche de mémoire de travail, (ii) l'âge des individus au cours de la tâche et (iii) la performance de la tâche pendant un état de repos. Trois cent quatre-vingt participants âgés (82 ans, 56% femmes) issus de la cohorte des Trois Cités de Montpellier ont été sélectionnés pour réaliser un examen d'IRMf comprenant une tâche de DIR (reconnaissance d'item en élément différé) et un état de repos. La tâche de DIR s'organisait en trois phases : (i) présentation – une, trois ou six lettres – (ii) rétention – écran blanc – et (iii) réponse – après la présentation d'une lettre cible, le participant indique si cette lettre cible faisait partie ou non de l'ensemble de départ. Dans une première partie, après avoir localisé les régions activées lors des trois phases de la tâche, nos analyses de covariance ont pu identifier, simultanément à la difficulté croissante de la tâche, une augmentation de l'activation dans les réseaux du central exécutif et de saillance pendant les trois phases de la tâche ainsi qu'une diminution dans le réseau du mode par défaut pendant la phase de stimulation et dans les régions limbiques et des ganglions de la base pendant la phase de rétention. Ces résultats suggèrent une interaction entre les réseaux d'augmentation et de diminution. Dans une deuxième partie, nous avons exploré l'effet de l'âge sur l'augmentation de l'activité simultanément avec la difficulté croissante de la tâche. Pendant la phase de stimulation, une réduction de l'activation dans le lobule pariétal gauche a été identifiée chez les individus très âgés par rapport aux individus âgés jeunes suggérant la mise en jeu d'un décalage antéro-postérieur lorsque l'âge augmente. Dans une troisième partie, les réseaux impliqués dans la mémoire de travail (central exécutif, saillance et mode par défaut) ont été mis en évidence pendant l'état de repos. Notre travail a montré que la connectivité fonctionnelle et la performance sont corrélées par : (i) une réduction au sein des réseaux de saillance et du mode par défaut suggérant une altération des processus mémoriels et attentionnels et (ii) une augmentation au sein du réseau du central exécutif évoquant l'implication d'un processus compensatoire. L'ensemble de ces résultats indiquent la présence de réorganisations cérébrales des réseaux neuronaux (saillance, central exécutif et mode par défaut) sous-tendant la mémoire de travail au cours du vieillissement cérébral normal. / Normal brain aging is characterized by a progressive decline in information processing ability in particular in the system of working memory. Therefore, it is essential to examine neural substrates underlying the working memory system which can be assessed by functional magnetic resonance imaging (fMRI). The aim of our work is to explore, in a large cohort of healthy elderly individuals, reorganizations in the networks in relation to (i) increase task load during a DIR (delayed item recognition) task, (ii) age during increase DIR task load and (iii) the performance in the DIR task during a resting state. Three hundred and eighty elderly participants (82 years, 56% women) from the Three-City cohort in Montpellier have been selected to perform an fMRI exam including a DIR task and a resting state. DIR task consisted of three phases: (i) stimulation – presentation of one, three or six letters - (ii) retention - blank screen to hold the stimulus items in mind - and (iii) probe - after the presentation of a target letter, the participant indicates whether or not this probe matched a letter in the study array. In the first work, using a covariance analysis, we observed, when the difficulty of the DIR task increases, simultaneously increased activation in salience and central executive networks during three phases separately of the DIR task and decreased activation in DMN during stimulation phase and in limbic regions and deep grey nuclei during retention phase. It may be hypothesized that salience and central executive networks interact in a complex way with DMN and limbic regions and deep grey nuclei. In the second work, age effects on load-dependent increases activations of the task were explored. Reduced activation in the left parietal lobe was identified in very old individuals compared to young old individuals during the stimulation phase suggesting an involvement of posterior–anterior shift with increasing age. In the third work, networks implicated in working memory (central executive, salience and the default mode networks) were highlighted by independent component analysis during the resting state. Our findings have confirmed that the functional connectivity and performance are related by: (i) a decreased in the both salience and the default mode networks and (ii) an increased in the central executive network. We can suggest that the decreased functional connectivity within the salience and the default mode networks could be due attentional and memory processes alterations and/or altered motivation. The increased functional connectivity within the central executive network could be related to compensatory mechanisms meanwhile elders would perform more poorly. All of these studies indicate that brain reorganizations of neural networks (salience, central executive and default mode) underlying working memory in normal brain aging.

Genetic and environmental protective factors and risks modulate brain structure and function in neurodegenerative diseases and their preclinical stages. We wanted to investigate whether the years of formal education, a proxy measure for cognitive reserve, would influence hippocampal structure in Alzheimer’s disease patients, and whether apolipoprotein Eε4 (APOE4) carrier status and a first-degree family history of the disease would change a possible association. Fifty-eight Alzheimer’s disease patients underwent 3T magnetic resonance imaging. We applied a cortical unfolding approach to investigate individual subregions of the medial temporal lobe. Among patients homozygous for the APOE4 genotype or carrying both APOE4 and family history risks, lower education was associated with a thinner cortex in multiple medial temporal regions, including the hippocampus. Our data suggest that the years of formal education and genetic risks interact in their influence on hippocampal structure in Alzheimer’s disease patients.

Genetic and environmental protective factors and risks modulate brain structure and function in neurodegenerative diseases and their preclinical stages. We wanted to investigate whether the years of formal education, a proxy measure for cognitive reserve, would influence hippocampal structure in Alzheimer’s disease patients, and whether apolipoprotein Eε4 (APOE4) carrier status and a first-degree family history of the disease would change a possible association. Fifty-eight Alzheimer’s disease patients underwent 3T magnetic resonance imaging. We applied a cortical unfolding approach to investigate individual subregions of the medial temporal lobe. Among patients homozygous for the APOE4 genotype or carrying both APOE4 and family history risks, lower education was associated with a thinner cortex in multiple medial temporal regions, including the hippocampus. Our data suggest that the years of formal education and genetic risks interact in their influence on hippocampal structure in Alzheimer’s disease patients.