The Influence of Carbon Dioxide on Brain Activity and Metabolism in Conscious Humans

Abstract

A better understanding of carbon dioxide (CO 2 ) effect on brain activity may have a profound impact on clinical studies using CO 2 manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO 2 , via inhalation of 5% CO 2 , may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO 2 ) by 13.4% ± 2.3% (N = 14) and, furthermore, the CMRO 2 change was proportional to the subject's end-tidal CO 2 (Et-CO 2 ) change. When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visualevoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO 2 inhalation.

Effect of Hypoxia and Hyperoxia on Cerebral Blood Flow, Blood Oxygenation, and Oxidative Metabolism

“…Once Y v is known, p v O 2 can also be estimated from the O 2 dissociation curve, although the dissolved O 2 in venous blood is virtually negligible compared with the hemoglobin-bound O 2 . Phase-contrast (PC) MRI was used to measure CBF (Xu et al, 2011). Consistent with TRUST MRI, PC MRI was also performed in the sagittal sinus.…”

The Contribution of Arterial Blood Gases in Cerebral Blood Flow Regulation and Fuel Utilization in Man at High Altitude

“…11 Conversely, older studies using positron emission tomography indicate that cerebral glucose metabolism might decrease at altitude in populations evolutionarily less adapted to HA 12 than the Sherpa in whom it is similar to SL dwellers at SL. 13 Studies in animals indicate decreased cerebral carbohydrate metabolism, 14 and in humans small decreases (~13%) in CMRO 2 with hypercapnia were reported by Xu et al, 15 although this is not a universal finding, 16 and has not been assessed using cerebral arteriovenous differences in humans at SL or at HA. It thus remains unclear whether the prevailing CBF after partial acclimatization is regulated by oxygen delivery, sustained hypocapnia, altered acid-base buffering, changes in cerebral metabolism or the balance between them all.…”

“…But, studies on human cerebral metabolism during hypercapnia have focused exclusively on CMRO 2 . 15,16,37 The study of Hertz and Paulson 36 is the only other study, to our knowledge, assessing cerebral substrate metabolism during acute hypercapnia in conscious humans (who required carotid angiography). They reported a decrease in mean a-vGlucose but there was no mention of a negative a-vGlucose difference in any subjects despite a similar magnitude of hypercapnia.…”

Quantitative mapping of cerebrovascular reactivity using resting-state BOLD fMRI: Validation in healthy adults

“…In addition, the various styles of breath-holding can introduce difficulties in comparing CVR values across populations. Moreover, undesirable perturbations in neuronal activity (Jain et al, 2011;Xu et al, 2011) due to the sometimes large PETCO 2 changes (Chen and Pike, 2010a) can compromise the accuracy of conventional CVR measures. More concerning are unwanted side effects of conventional CVR tasks, which may be harmful in certain patient types (Karakaya et al, 2006;Laine et al, 1986).…”