Task-dependent activity and connectivity predict episodic memory network-based responses to brain stimulation in healthy aging.

BACKGROUND Transcranial magnetic stimulation (TMS) can affect episodic memory, one of the main cognitive hallmarks of aging, but the mechanisms of action remain unclear. OBJECTIVES To evaluate the behavioral and functional impact of excitatory TMS in a group of healthy elders. METHODS We applied a paradigm of repetitive TMS - intermittent theta-burst stimulation - over left inferior frontal gyrus in healthy elders (n = 24) and evaluated its impact on the performance of an episodic memory task with two levels of processing and the associated brain activity as captured by a pre and post fMRI scans. RESULTS In the post-TMS fMRI we found TMS-related activity increases in left prefrontal and cerebellum-occipital areas specifically during deep encoding but not during shallow encoding or at rest. Furthermore, we found a task-dependent change in connectivity during the encoding task between cerebellum-occipital areas and the TMS-targeted left inferior frontal region. This connectivity change correlated with the TMS effects over brain networks. CONCLUSIONS The results suggest that the aged brain responds to brain stimulation in a state-dependent manner as engaged by different tasks components and that TMS effect is related to inter-individual connectivity changes measures. These findings reveal fundamental insights into brain network dynamics in aging and the capacity to probe them with combined behavioral and stimulation approaches.