title: Dependence of BOLD signal fluctuation on arterial blood CO2 and O2: Implication for resting-state functional connectivity.
abstract: Blood oxygenation level dependent (BOLD) functional MRI signal is known to be modulated by the CO2 level. Typically only end-tidal CO2, rather than the arterial partial pressure of CO2 (paCO2), was measured while the arterial partial pressure of O2 (paO2) level was not controlled due to free breathing, making their contribution not separable. Especially, the influences of paO2 and paCO2 on resting-state functional connectivity are not well studied. In this study, we investigated the relationship between paCO2 and resting as well as stimulus-evoked BOLD signals under hyperoxic and hypercapnic manipulation with tight control of arterial paO2. Rats under isoflurane anesthesia were subjected to six inspired gas conditions: 47% O2 in air (Normal), adding 1%, 2% or 5% CO2, carbogen (95% O2/5% CO2), and 100% O2. Somatosensory BOLD activation was significantly increased under 100% O2, while reduced with increased paCO2 levels. However, while resting BOLD connectivity pattern expanded and bilateral correlation increased under 100% O2, the correlation coefficient between the left and right somatosensory cortex was generally not dependent on paCO2 or paO2. Interestingly, the correlation in 0.04-0.07Hz range significantly increased with CO2 levels. Intracortical electrophysiological recordings showed a similar trend as the BOLD but the neurovascular coupling varied. The results suggest that paO2 and paCO2 together rather than paCO2 alone alter the BOLD signal. The response is not purely vascular in nature but has strong neuronal origins. This should be taken into consideration when designing calibrated BOLD experiment and interpreting functional connectivity data especially in aging, under drug, or neurological disorders.
authors.affiliation: Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore.
authors.forename: Fatima A
authors.initials: FA
authors.lastname: Nasrallah
authors.affiliation: Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore.
authors.forename: Ling Yun
authors.initials: LY
authors.lastname: Yeow
authors.affiliation: Department of Biomedical Engineering, New Jersey Institute of Technology, NJ, USA.
authors.forename: Bharat
authors.initials: B
authors.lastname: Biswal
authors.affiliation: Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore; Clinical Imaging Research Centre, National University of Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: kaichuang@gmail.com.
authors.forename: Kai-Hsiang
authors.initials: KH
authors.lastname: Chuang
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001769:Blood / Q000378:metabolism*; D001784:Blood Gas Analysis; D001931:Brain Mapping; D002245:Carbon Dioxide / Q000008:administration & dosage; D005073:Evoked Potentials, Somatosensory; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000008:administration & dosage; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D013003:Somatosensory Cortex / Q000378:metabolism / Q000502:physiology*; D055698:Touch Perception / Q000502:physiology*
chemical_list: D002245:Carbon Dioxide; D010100:Oxygen
keywords: CO(2); Carbogen; EEG; Functional MRI; Functional connectivity; Hypercapnia; Hyperoxia; Neurovascular coupling; Resting state