Prefrontal executive function enhanced by prior acute inhalation of low-dose hypoxic gas: Modulation via cardiac vagal activity

Today, diverse psychophysiological stresses, such as severe time constraints and busy lifestyles, contribute to cardiac parasympathetic dysfunction, potentially leading to mental health issues and declines in critical executive functions. It is essential to develop accessible methods of enhancing cardiac vagal activity (CVA) to mitigate these adverse effects. We previously demonstrated that inhaling low-dose hypoxic gas (FIO₂: 13.5 %) for 10 min acts as a hormetic stressor, inducing a supercompensation effect in CVA post-hypoxia. Since CVA is a key mediator of brain-heart communication in that it influences executive functions by interacting with the left dorsolateral prefrontal cortex (L-DLPFC), increasing CVA may enhance cognitive ability. We hypothesized that acute low-dose hypoxia leads to enhanced executive function via CVA modulation. Twenty-six individuals participated in both normobaric hypoxia (NH; FIO₂: 13.5 %) and normoxia (NN; ambient air) conditions. CVA, measured through heart rate variability, was analyzed three times: pre-hypoxia/normoxia, hypoxia/normoxia, and post-hypoxia/normoxia. Executive function was assessed using the Stroop task before and after exposure, and prefrontal cortex activity during the task was monitored using multichannel functional near-infrared spectroscopy. A supercompensation of CVA occurred concomitantly with a reduction in heart rate following hypoxic gas inhalation. Stroop performance improved with increased task-related activation of the L-DLPFC in the NH condition. Causal mediation analysis revealed that the post-hypoxia enhancement of CVA mediated improvements in Stroop performance and increased L-DLPFC activation. These findings strongly support our hypothesis that the enhancement of CVA following hormetic hypoxic stress contributes to improved executive function, broadening the scope of neurocognitive approaches for effectively enhancing executive function.