Abstract
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 codes 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 minutes 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-minute post-stimulation period. The results provide insight into the physiological foundations of age-related cognitive impairment and contribute groundwork for future non-pharmacological interventions targeting aspects of cognitive decline.
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