TY - JOUR T1 - Causal Relationships Underlying Episodic Memory Network Dynamics in Older Adults JF - bioRxiv DO - 10.1101/061267 SP - 061267 AU - Simon W. Davis AU - Bruce Luber AU - David L.K. Murphy AU - Sarah H. Lisanby AU - Roberto Cabeza Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/06/29/061267.abstract N2 - The most reliable finding in functional neuroimaging studies of cognitive aging is a more widespread brain activity pattern in older than younger adults. The additional regions recruited by older adults are functionally connected to core task-network regions, and frequently contribute to task performance in this group, suggesting that older adults may compensate for core task-network deficits by expanding the task-related network. This hypothesis is difficult to resolve with functional neuroimaging alone, because it is unclear both how to define reliable causal trends in which connections are important (e.g., local versus indirect connections). To address this problem we examined functional connectivity measures as quantified by a region's local within-module degree (WMD), or their between-module degree (BMD) between distant cortical communities. We combined these graph theoretical measures with diffusion tensor imaging (DTI) and repetitive transcranial magnetic stimulation (rTMS) in order to resolve the central hypothesis. We applied enhancing (5Hz) or impairing (1Hz) rTMS to a core episodic encoding region, the left prefrontal cortex (PFC) and predicted that (1) if older adults compensate for local deficits by boosting BMD, then enhancing left PFC function should reduce BMD, whereas impairing it, should increase BMD and (2) that this effect should be correlated with DTI measures of white-matter integrity. Both predictions were confirmed, supporting for the compensatory interpretation of an expanded task network in older adults. More generally, the results illustrate the power of combining rTMS with functional and structural connectivity measures to investigate age-related changes in network architecture.Significance Statement An integrated account of the functional dynamics of cortical connectivity in aging is incomplete. Our approach is to unite network theory, brain stimulation, and diffusion tractography in order determine how the aging brain adapts to local changes in cortical reactivity during episodic encoding. We found that aging brains adapt their local and distal connectivity patterns in a frequency-selective manner, and that these changes are constrained by white matter connectivity. These results help to advance a mechanistic understanding of the network dynamics associated with episodic memory performance, and suggest novel interventions to improve memory functioning in later adulthood. ER -