title: Arterial CO2 Fluctuations Modulate Neuronal Rhythmicity: Implications for MEG and fMRI Studies of Resting-State Networks.
abstract: A fast emerging technique for studying human resting state networks (RSNs) is based on spontaneous temporal fluctuations in neuronal oscillatory power, as measured by magnetoencephalography. However, it has been demonstrated recently that this power is sensitive to modulations in arterial CO2 concentration. Arterial CO2 can be modulated by natural fluctuations in breathing pattern, as might typically occur during the acquisition of an RSN experiment. Here, we demonstrate for the first time the fine-scale dependence of neuronal oscillatory power on arterial CO2 concentration, showing that reductions in alpha, beta, and gamma power are observed with even very mild levels of hypercapnia (increased arterial CO2). We use a graded hypercapnia paradigm and participant feedback to rule out a sensory cause, suggesting a predominantly physiological origin. Furthermore, we demonstrate that natural fluctuations in arterial CO2, without administration of inspired CO2, are of a sufficient level to influence neuronal oscillatory power significantly in the delta-, alpha-, beta-, and gamma-frequency bands. A more thorough understanding of the relationship between physiological factors and cortical rhythmicity is required. In light of these findings, existing results, paradigms, and analysis techniques for the study of resting-state brain data should be revisited.
  
  
  
  In this study, we show for the first time that neuronal oscillatory power is intimately linked to arterial CO2 concentration down to the fine-scale modulations that occur during spontaneous breathing. We extend these results to demonstrate a correlation between neuronal oscillatory power and spontaneous arterial CO2 fluctuations in awake humans at rest. This work identifies a need for studies investigating resting-state networks in the human brain to measure and account for the impact of spontaneous changes in arterial CO2 on the neuronal signals of interest. Changes in breathing pattern that are time locked to task performance could also lead to confounding effects on neuronal oscillatory power when considering the electrophysiological response to functional stimulation.
authors.affiliation: Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff CF10 3AT, United Kingdom, DriverI@cardiff.ac.uk.
authors.forename: Ian D
authors.identifier: 0000-0001-6815-0134
authors.initials: ID
authors.lastname: Driver
authors.affiliation: Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff CF10 3AT, United Kingdom.
authors.forename: Joseph R
authors.identifier: 0000-0002-2141-7513
authors.initials: JR
authors.lastname: Whittaker
authors.affiliation: Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff CF10 3AT, United Kingdom, Sir Peter Mansfield Imaging Centre, Clinical Neurology, School of Medicine, University of Nottingham, Nottingham NG7 2RD, United Kingdom, and.
authors.forename: Molly G
authors.identifier: 0000-0001-7257-9646
authors.initials: MG
authors.lastname: Bright
authors.affiliation: Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff CF10 3AT, United Kingdom, Schools of Pharmacy and Psychology, Auckland University, Auckland 1142, New Zealand.
authors.forename: Suresh D
authors.initials: SD
authors.lastname: Muthukumaraswamy
authors.affiliation: Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff CF10 3AT, United Kingdom.
authors.forename: Kevin
authors.identifier: 0000-0002-6516-313X
authors.initials: K
authors.lastname: Murphy
mesh_terms: D000328:Adult; D001683:Biological Clocks / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging*; D001931:Brain Mapping; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D015225:Magnetoencephalography; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging*; D009474:Neurons / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D012146:Rest
chemical_list: D002245:Carbon Dioxide; D010100:Oxygen
keywords: cortical oscillations; functional connectivity; hypercapnia; magnetoencephalography; physiological noise