Abstract Rationale A number of rigorous human studies raise concerns about the potential impact of inhaled CO2 on complex cognition tasks, including piloting a flight simulator, at commonly encountered concentrations, 2,000-3,000 ppm. This is well below the OSHA PEL of 5,000 PPM. Such concentrations are frequently present in poorly ventilated school classrooms and conference rooms. Evidence from our human exposure laboratory and previous rodent inhalation studies suggests that immune-metabolic alterations in neutrophils may mediate this neurocognitive dysfunction. The present report further investigates the mechanisms by which elevated CO2 impairs complex cognitive function, adding brain functional Magnetic Resonance Imaging (fMRI) evidence to previous metabolic observations of neutrophil activation. Methods 24 healthy participants were exposed to either 600 ppm (control) or 2500 ppm CO2 for 2 hours in a crossover double-blind, randomized order study. Cognitive performance was assessed during exposure using the Strategic Management Simulations (SMS) test. Neutrophils were isolated four hours after exposure onset and analyzed for time to peak oxidative burs (TTP) after PMA stimulation. A subset of 12 participants underwent brain fMRI while completing the Multi-Source Interference Task (MSIT), a selective attention task sensitive to cognitive control. Results We found a strong correlation between TTP and SMS performance, supporting the hypothesis that neutrophil activation contributes to cognitive impairment following CO2 exposure. MSIT performance during the fMRI was not altered by prior CO2 exposure, but fMRI revealed significantly reduced brain activation during incongruent (vs. congruent) trials in brain regions known to be associated with MSIT performance. These regions included the right inferior frontal junction, left motor cortex, cuneus, and left supramarginal gyrus. Regression analyses linked the decline in brain activation to changes in both MSIT performance and TTP, with peak associations in the right inferior frontal junction and right inferior parietal sulcus. Conclusions Together, these findings provide preliminary but compelling evidence that real world CO2 exposure impairs cognitive function through immune-driven disruption of brain network activity, warranting further investigation into neuroimmune pathways involved in environmental CO2 toxicity. This abstract is funded by: NIEHS
Kipen et al. (Fri,) studied this question.