Age-Related Changes in BOLD Activation Pattern in Phonemic Fluency Paradigm: An Investigation of Activation, Functional Connectivity and Psychophysiological Interactions

Christian La, Camille Garcia-Ramos, Veena A. Nair, Timothy B. Meier, Dorothy Farrar-Edwards, Rasmus Birn, Mary E. Meyerand, Vivek Prabhakaran

Healthy aging is associated with decline of cognitive functions. However, even before those declines become noticeable, the neural architecture underlying those mechanisms has undergone considerable restructuring and reorganization. During performance of a cognitive task, not only have the task-relevant networks demonstrated reorganization with aging, which occurs primarily by recruitment of additional areas to preserve performance, but the task-irrelevant network of the "default-mode" network (DMN), which is normally deactivated during task performance, has also consistently shown reduction of this deactivation with aging. Here, we revisited those age-related changes in task-relevant (i.e., language system) and task-irrelevant (i.e., DMN) systems with a language production paradigm in terms of task-induced activation/deactivation, functional connectivity, and context-dependent correlations between the two systems. Our task fMRI data demonstrated a late increase in cortical recruitment in terms of extent of activation, only observable in our older healthy adult group, when compared to the younger healthy adult group, with recruitment of the contralateral hemisphere, but also other regions from the network previously underutilized. Our middle-aged individuals, when compared to the younger healthy adult group, presented lower levels of activation intensity and connectivity strength, with no recruitment of additional regions, possibly reflecting an initial, uncompensated, network decline. In contrast, the DMN presented a gradual decrease in deactivation intensity and deactivation extent (i.e., low in the middle-aged, and lower in the old) and similar gradual reduction of functional connectivity within the network, with no compensation. The patterns of age-related changes in the task-relevant system and DMN are incongruent with the previously suggested notion of anti-correlation of the two systems. The context-dependent correlation by psycho-physiological interaction (PPI) analysis demonstrated an independence of these two systems, with the onset of task not influencing the correlation between the two systems. Our results suggest that the language network and the DMN may be non-dependent systems, potentially correlated through the re-allocation of cortical resources, and that aging may affect those two systems differently.