Working memory revived in older adults by synchronizing rhythmic brain circuits

Abstract

Published in final edited form as: Nat Neurosci. 2019 May ; 22(5): 820–827. doi:10.1038/s41593-019-0371-x.Understanding normal brain aging and developing methods to maintain or improve cognition in older adults are major goals of fundamental and translational neuroscience. Here we show a core feature of cognitive decline—working-memory deficits—emerges from disconnected local and long-range circuits instantiated by theta–gamma phase–amplitude coupling in temporal cortex and theta phase synchronization across frontotemporal cortex. We developed a noninvasive stimulation procedure for modulating long-range theta interactions in adults aged 60–76 years. After 25 min of stimulation, frequency-tuned to individual brain network dynamics, we observed a preferential increase in neural synchronization patterns and the return of sender–receiver relationships of information flow within and between frontotemporal regions. The end result was rapid improvement in working-memory performance that outlasted a 50 min post-stimulation period. The results provide insight into the physiological foundations of age-related cognitive impairment and contribute to groundwork for future non-pharmacological interventions targeting aspects of cognitive decline.Accepted manuscrip