Journal
ENEURO
Volume 6, Issue 6, Pages -Publisher
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0047-19.2019
Keywords
anterior cingulate cortex; functional connectivity; graph theory; prefrontal cortex; working memory
Categories
Funding
- National Institutes of Health/National Institute on Aging [R01-AG-049722, P50-AG-047266]
- McKnight Brain Research Foundation
- Advanced Magnetic Resonance Imaging and Spectroscopy facility (National Science Foundation) [DMR-1157490]
- Advanced Magnetic Resonance Imaging and Spectroscopy facility (State of Florida)
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The functional connectome reflects a network architecture enabling adaptive behavior that becomes vulnerable in advanced age. The cellular mechanisms that contribute to altered functional connectivity in old age, however, are not known. Here we used a multiscale imaging approach to link age-related changes in the functional connectome to altered expression of the activity-dependent immediate-early gene Arc as a function of training to multitask on a working memory (WM)/biconditional association task (BAT). Resting-state fMRI data were collected from young and aged rats longitudinally at three different timepoints during cognitive training. After imaging, rats performed the WM/BAT and were immediately sacrificed to examine expression levels of Arc during task performance. Aged behaviorally impaired, but not young, rats had a subnetwork of increased connectivity between the anterior cingulate cortex (ACC) and dorsal striatum (DS) that was correlated with the use of a suboptimal response-based strategy during cognitive testing. Moreover, while young rats had stable rich-club organization across three scanning sessions, the rich-club organization of old rats increased with cognitive training. In a control group of young and aged rats that were longitudinally scanned at similar time intervals, but without cognitive training, ACC-DS connectivity and rich-club organization did not change between scans in either age group. These findings suggest that aberrant large-scale functional connectivity in aged animals is associated with altered cellular activity patterns within individual brain regions.
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