Aging hippocampus and cognitive control in health and MCI - ABSTRACT/SUMMARY Comprising proactive (goal-directed) and reactive (stimulus-driven) processes, cognitive control is critical to daily functions for older adults. However, how aging influences proactive and reactive control remains unclear, with studies of the AX-continuous performance task (AX-CPT) reporting impaired proactive but intact reactive control and studies of the stop signal task (SST) reporting the opposite. Further, the structural and functional cerebral bases of age-dependent changes in cognitive control have not been studied systematically. We aim to employ an innovative experimental design to address this gap in research. On the basis of the literature and our preliminary findings, we will investigate hippocampal dysfunction and impairment in contextual processing as a determinant of cognitive control deficits during aging and in individuals with mild cognitive impairment (MCI). Specifically, we aim to examine how contextual representation (i.e., explicit stimulus-response mapping in the AX-CPT and implicit inference in the SST) rather than motor demand (i.e., omnipresent response in the AX-CPT and conditional response in the SST) contribute to age-related deficits in cognitive control. By including two variants of the behavioral tasks, the AXn-CPT, where non-target response is replaced with no response, and SSTr, where stop signal instructs an alternative motor response instead of no response, we propose to distinguish the psychological constructs that dictate age- and MCI-related changes in proactive and reactive control. By combining the behavioral tasks and fMRI we will investigate how structural and functional brain changes account for age- and MCI-related alterations in cognitive control. First, we hypothesize that, if contextual representation accounts for the effects of aging and MCI, aging will be associated with impaired proactive and intact reactive control in both AX-CPT and AXn-CPT, and with intact proactive and impaired reactive control in both SST and SSTr. Conversely, if motor demand accounts for the effects, older adults will show impaired proactive and intact reactive control in AX-CPT and SSTr, as well as intact proactive and impaired reactive control in SST and AXn-CPT. Second, we hypothesize that deficient control is associated with disrupted activation and functional connectivity in the hippocampus and other task-related regions. In particular, the anterior and posterior hippocampus may play distinct roles in supporting reactive and proactive control. Third, we hypothesize age-related decreases in hippocampal and prefrontal cortical gray matter volume and will explore how this structural deficit relates to age-dependent alterations in functional activations during cognitive control. Further, disproportionate volumetric decline and altered activations in the hippocampus may be associated with deteriorated cognitive control in MCI. Together, the proposed study will delineate the psychological and neural processes underlying executive control dysfunction in aging and MCI, addressing a critical gap of research in aging neuroscience. We hope that the findings would inform the care of older adults in health and illness.
