No robust add-on effects of prefrontal theta-gamma tACS to cognitive training on episodic memory in non-demented older adults

Abstract

Objective: In order to develop new strategies that counteract age-related cognitive decline, this study explores the efficacy of combined computerized cognitive training (CCT) and prefrontal theta-gamma transcranial alternating current stimulation (tACS) to enhance episodic memory functions in older adults.

Methods: 77 non-demented older adults were randomly assigned to receive either active or sham peak-coupled theta-gamma tACS targeting the prefrontal cortex while undergoing CCT. Global cognition and episodic memory performance was assessed before, after, and three months after a 16-day intervention.

Results: The primary analysis demonstrated significant improvements in multiple episodic memory measures across both intervention groups, with no significant differences observed between groups. However, follow-up post-hoc tests revealed a significant enhancement in the delayed verbatim score of a story recall test following active tACS, but not after sham tACS. Global cognition was unaffected in both groups.

Conclusion: Our findings do not provide evidence for robust add-on effects of prefrontal theta-gamma tACS to CCT on non-trained episodic memory skills in non-demented older adults.

Significance: Multi-session prefrontal peak-coupled theta-gamma tACS with CCT is not superior to sham stimulation with CCT to improve episodic memory in older adults.

Keywords: Aging; Cognition; Cognitive training; Cross-frequency coupling; Theta-gamma coupling; Transcranial alternating current stimulation (tACS).