Abstract
BACKGROUND: Forty Hz light flicker has shown promise in mitigating cognitive impairments, though its mechanisms remain unclear. AIMS: This study aimed to use perioperative neurocognitive dysfunction (PND) as a unique model of neural damage to provide a broader understanding of the neural mechanisms underlying the cognitive improvements associated with 40 Hz visual stimulation and offer new insights into the clinical application of PND treatment. MATERIALS AND METHODS: Postoperative cognitive function was assessed through behavioral tests. Male and female mice received various visual light flicker stimuli, including 40 Hz, random, continuous, or no light. Local field potentials were recorded from the hippocampal dentate gyrus (DG) and primary visual cortex. RESULTS: Our results show that among the stimuli, only the 40 Hz flicker improved cognitive function, impaired by anesthesia or surgery. Intraoperative 40 Hz stimulation activated the primary visual cortex and was correlated with enhanced gamma coherence between this region and the hippocampal DG, a coherence that surgery itself notably reduced. This preserved functional connectivity. Additionally, hippocampal DG activity was enhanced, particularly in the gamma frequency range. CONCLUSION: Our results suggest that 40 Hz flicker mitigates anesthesia/surgery-induced cognitive deficits, potentially through modulating gamma coherence between the visual cortex and hippocampus. These findings provide insights into PND prevention and the neural mechanisms underlying 40 Hz-induced cognitive benefits.