RT Journal Article SR Electronic T1 Multiscale Imaging Reveals Aberrant Functional Connectome Organization and Elevated Dorsal Striatal Arc Expression in Advanced Age JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0047-19.2019 DO 10.1523/ENEURO.0047-19.2019 VO 6 IS 6 A1 Luis M. Colon-Perez A1 Sean M. Turner A1 Katelyn N. Lubke A1 Marjory Pompilus A1 Marcelo Febo A1 Sara N. Burke YR 2019 UL http://www.eneuro.org/content/6/6/ENEURO.0047-19.2019.abstract AB 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.