Corrélats neurofonctionnels des habiletés lexico-sémantiques selon le décours et les expériences de vie

The aging of societies worldwide comes with both immense opportunities as well as numerous challenges regarding health and wellness. As reported by older adults, quality of life in aging is heavily dependent upon cognitive health. A better understanding of the constituents of cognitive health is thus a central piece of the scientific challenge that awaits neuroscientists.  For a cost-effective functioning in everyday cognitive activities, brain regions synchronize their activity one with another, as is measured by functional connectivity using neuroimaging. Functional connectivity has allowed for the recognition of a relatively stable architecture in charge of cognitive processes. This functional organization would be in large part determined by the architecture present at “rest” (the unconstrained spontaneous activity), but would also be modulated by the cognitive activity and by the cognitive demand in task-specific networks. The current understanding of the brain reorganization in aging relies mostly on either resting-state studies, or on a smaller number of studies that explored cognitive abilities typically declining with age. This literature led to the development of domain-general models and concepts regarding cognitive aging. Yet, little is known about task-specific patterns in functional connectivity with age. For example, lexical-semantic abilities are characterized by general preservation of performance in aging, therefore offering a potentially privileged window to observe efficient cognitive mechanisms. The exploration of task-specific characteristics could thus offer a new insight on neurofunctional mechanisms that define healthy aging, including potential reserve phenomenon. The general aim of this thesis, articulated in three studies, is to describe and compare the effect of age on functional connectivity patterns during lexico-semantic tasks and at rest, as well as to characterize the influence of task complexity and life experiences on the relationship between age and cognitive performance.  The goal of the first study was to describe the age-related changes in functional connectivity using three language tasks in a large cohort of aging adults [18-85 years old] and to compare these changes with those observed in a resting state. Results show that age-related differences vary from one paradigm to another and that resting-state present very distinct pattern when compared with tasks. Notably, regions of the language network show age-related increases in connectivity while only age-related decreases characterize resting-state. These results remained stable even after manipulation of the model’s confounding variables, suggesting a certain robustness.   Task-induced functional connectivity thus holds a potential to reveal neurofunctional processes that are distinctly adapted to the cognitive state. In consequence, a precise neurofunctional characterization for a given cognitive activity may benefit from a methodological fine-tuning. Such manipulation of the task may reveal neurofunctional mechanisms that support preserved cognitive abilities. For example, task paradigm allows the use of a sample and task-specific template instead of generic -resting-state- atlases, or the manipulation of the cognitive demand level. The goal of the second study was to describe the age-related changes of the functional connectivity patterns during the accomplishment of a cognitive task that is typically preserved in healthy aging, as well as to compare age-related differences under higher task demand, defined by lexical frequency. Results suggest both age and task-specific mechanisms. Older adults show a complex array of differences in functional connectivity architecture, especially so in speech motor regions, but also in the form of increased segregation of regions classically attributed to semantic processing. Only a few regions show a significant interaction effect between intrinsic task demand and age-related differences in functional connectivity. Altogether, the findings from the first two studies confirm the complementary interest of task-induced functional connectivity analysis to uncover the brain organization that subserves lexico-semantic abilities during healthy aging.  Yet, little is known about what processes underly inter-individual differences in performance. In the investigation of preserved performance in aging, the impact of cognitively stimulating life experiences has drawn many interests in the past 20 years. Life experiences were indeed demonstrated to contribute to the preservation of cognitive performance in healthy aging and in the early stages of neurodegenerative diseases. This mechanism is suspected of operating through an indirect relationship between life experiences and cognitive activity via neural activity. It may also be mediated by the individual capacity to cope with the demand of the task. The impact of such lifetime experience on naming abilities --- amongst the best-preserved with age --- is still unknown.   The goal of the third study was thus to describe the direct and indirect relationships between lifelong activities (i.e., education, occupation, everyday activities), functional connectivity, and task performance in older individuals. Results show that life experiences interact with functional connectivity during successful word naming among older individuals. An interaction with task demand was also noted in some brain regions, suggesting demand-dependent neural mechanisms.   In conclusion, functional connectivity proves to be sensitive to the actual cognitive state, supporting the use of carefully designed paradigms to answer specific questions about cognitive aging. During the successful performance of a word naming task, older adults show a task-specific use of the brain connectome. While cognitively stimulating life experiences interact with functional connectivity in older adults, it appears poorly related to task performance in the context of preserved naming abilities. These findings offer an alternative perspective to previous reports of domain-general neural mechanisms in aging. Task and sample-specific designs may reveal useful to reach a complete characterization of successful cognitive processes in healthy aging.

Keyphrases: neuroimagerie, aging, language, semantics, neuroimaging, functional connectivity, task-induced functional connectivity, resting-state, life experiences, neurocognitive reserve