Dynamique cérébrale et réserve cognitive 
en situation d’attention sélective dans le vieillissement normal et les troubles de la cognition : approche neurofonctionnelle

Normal aging and disrupt selective visual attention – the ability to focus perceptual mechanisms on target stimuli by neglecting irrelevant stimuli. These modifications are accompanied by brain reorganization on both interhemispheric (hemispheric asymmetry reduction) and intrahemispheric (posterior-anterior shift) dimensions. However, the mechanisms underlying this brain reorganization in the context of visual attention in normal aging and Alzheimer’s disease remain largely unknown. The goal of this dissertation is to better understand the nature of brain reorganization for visual selective attention, as well as the functional neural changes and the anatomical modification in normal aging and in cognitive impairment in nthe ederly. In normal aging, this research focuses on the nature of the brain reorganization (interhemispheric vs. intrahemispheric) in the context of visual selective attention and based on the cognitive reserve model to differentiate the underlying mechanisms (neural reserve vs. neural compensation). It also focuses on Alzheimer’s disease in the context of interhemispheric dynamics and its main anatomical substrate, the corpus callosum. Throughout this dissertation, the substrate (functional and anatomical) of brain reorganization is examined by manipulating the cognitive demand associated with the tasks to better understand the mechanisms applied to cope with normal aging and cognitive impairment.  The first chapter introduces the concepts of selective attention, neurofunctional changes in normal aging and cognitive impairment, and the cognitive reserve model before introducing the present research topic.  The second chapter (Article 1) reviews the contribution of hemispheric coupling to the preservation of cognitive abilities with age and its uncoupling in Alzheimer’s disease. In this review, the variable contribution of the adaptive callosal mechanism is discussed with reference to successful aging and Alzheimer’s disease.  The third (Article 2) and fourth chapters (Article 3) report studies conducted with functional magnetic resonance imaging (fMRI). The purpose of these studies was to investigate to what extent and how the neural reserve and neural compensation mechanisms contribute to coping with normal aging in two contexts of visual selective attention: simple perceptual processing and more complex naming processing. In both studies, the complexity of processes was also manipulated by varying the attentional load related to the number of stimuli to be processed (low: 3 letters vs. high: 5 letters). The results for the perceptual matching study, reported in the third chapter, support the neural compensation hypothesis of cognitive reserve, as the activations regions underlying task performance differed in the younger and older groups. The older group recruited bilateral frontal superior gyri more than the younger one, as in the PASA (posterior-anterior shift in aging) phenomenon, from the lowest attentional load level. In addition, the elderly were found to use compensation and neural reserve concurrently to cope with increasing attentional load for perceptual processing. The results for the naming matching study, reported in the fourth chapter, indicate a load-dependant PASA, supporting the hypothesis that an enhancement of compensatory mechanism is required for the most complex processing.  The fifth chapter (Article 4) presents studies investigating the interhemispheric dynamic, using variants of the letter matching paradigm, where cognitive demand is parametrically varied, along with 3D callosal total and regional volume measured, in individuals with Alzheimer disease and amnestic-mild cognitive impairment as well as age-matched healthy individuals. The results show that the relationship between the corpus callosum volume and the across-field advantage emerges for the lowest cognitive demand level in participants with Alzheimer disease but exclusively at high cognitive demand levels in normal aging; this suggests the existence of an interhemispheric compensation mechanism in Alzheimer disease based on the integrity of the corpus callosum and similar processes to those that allow the normal aging brain to cope with cognitive demand. These mechanisms are deficient in amnestic-mild cognitive impairment individuals in the high attentional load condition, due to callosal atrophy.  In chapter six the nature of mechanisms to cope with aging and cognitive impairment is discussed, addressing the two main dimensions of brain reorganization: intrahemispheric and interhemispheric. In normal aging, cerebral reorganization of visual selective attention implies an intrahemispheric PASA phenomenon based on neural compensation. To cope with increased cognitive demand, neural reserve can also be recruited in basic perceptual processing, while the recruitment of compensation mechanisms increases in more complex processing of visual selective attention. Our study suggests that compensation and reserve are flexible, adaptive and deployed according to the cognitive demand and the type of processing required. In cognitive impairment, our study suggests the existence of an interhemispheric compensation mechanism in Alzheimer’s disease based on integrity of the corpus callosum and similar processes to those that allow the normal aging brain to cope with cognitive demand. This study provides evidence that interhemispheric interactions, supported by the corpus callosum, constitute a flexible mechanism that can improve the brain’s ability to handle processing demands and thus may compensate for the neural decline in Alzheimer’s disease in low cognitive demand situations.

Keyphrases: Neuroimagerie, Visual selective attention, Cerebral reorganization, Neural reserve, Neural compensation, Normal aging, Alzheimer disease, Inter-hemispheric dynamic, Corpus Callosum, Neuroimagery, Visual Divided Field