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

Abstract

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.

Keywords: Aging; Episodic memory; Functional magnetic resonance imaging; Level of processing; Transcranial magnetic stimulation.