Touchscreen-Based Cognitive Training Alters Functional Connectivity Patterns in Aged But Not Young Male Rats

Age-related cognitive decline is related to cellular and systems-level disruptions across multiple brain regions. Because age-related cellular changes within different structures do not show the same patterns of dysfunction, interventions aimed at optimizing function of large-scale brain networks may show greater efficacy at improving cognitive outcomes in older adults than traditional pharmacotherapies. The current study aimed to leverage a preclinical rat model of aging to determine whether cognitive training in young and aged male rats with a computerized paired-associates learning (PAL) task resulted in changes in global resting-state functional connectivity. Moreover, seed-based functional connectivity was used to examine resting state connectivity of cortical areas involved in object-location associative memory and vulnerable in old age, namely the medial temporal lobe (MTL; hippocampal cortex and perirhinal cortex), retrosplenial cortex (RSC), and frontal cortical areas (prelimbic and infralimbic cortices). There was an age-related increase in global functional connectivity between baseline and post-training resting state scans in aged, cognitively trained rats. This change in connectivity following cognitive training was not observed in young animals, or rats that traversed a track for a reward between scan sessions. Relatedly, an increase in connectivity between perirhinal and prelimbic cortices, as well as reduced reciprocal connectivity within the RSC, was found in aged rats that underwent cognitive training, but not the other groups. Subnetwork activation was associated with task performance across age groups. Greater global functional connectivity and connectivity between task-relevant brain regions may elucidate compensatory mechanisms that can be engaged by cognitive training.