Multiscale imaging reveals aberrant functional connectome organization and elevated dorsal striatal arc expression in advanced age

Luis M. Colon-Perez, Sean M. Turner, Katelyn N. Lubke, Marjory Pompilus, Marcelo Febo, Sara N. Burke

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish
Article numberENEURO.0047-19.2019
JournaleNeuro
Volume6
Issue number6
DOIs
StatePublished - 1 Nov 2019

Keywords

  • Anterior cingulate cortex
  • Functional connectivity
  • Graph theory
  • Prefrontal cortex
  • Working memory

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