title: Evidence that the negative BOLD response is neuronal in origin: a simultaneous EEG-BOLD-CBF study in humans.
abstract: Unambiguous interpretation of changes in the BOLD signal is challenging because of the complex neurovascular coupling that translates changes in neuronal activity into the subsequent haemodynamic response. In particular, the neurophysiological origin of the negative BOLD response (NBR) remains incompletely understood. Here, we simultaneously recorded BOLD, EEG and cerebral blood flow (CBF) responses to 10 s blocks of unilateral median nerve stimulation (MNS) in order to interrogate the NBR. Both negative BOLD and negative CBF responses to MNS were observed in the same region of the ipsilateral primary sensorimotor cortex (S1/M1) and calculations showed that MNS induced a decrease in the cerebral metabolic rate of oxygen consumption (CMRO2) in this NBR region. The ∆CMRO2/∆CBF coupling ratio (n) was found to be significantly larger in this ipsilateral S1/M1 region (n=0.91±0.04, M=10.45%) than in the contralateral S1/M1 (n=0.65±0.03, M=10.45%) region that exhibited a positive BOLD response (PBR) and positive CBF response, and a consequent increase in CMRO2 during MNS. The fMRI response amplitude in ipsilateral S1/M1 was negatively correlated with both the power of the 8-13 Hz EEG mu oscillation and somatosensory evoked potential amplitude. Blocks in which the largest magnitude of negative BOLD and CBF responses occurred therefore showed greatest mu power, an electrophysiological index of cortical inhibition, and largest somatosensory evoked potentials. Taken together, our results suggest that a neuronal mechanism underlies the NBR, but that the NBR may originate from a different neurovascular coupling mechanism to the PBR, suggesting that caution should be taken in assuming the NBR simply represents the neurophysiological inverse of the PBR.
authors.affiliation: Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK; Birmingham University Imaging Centre, School of Psychology, University of Birmingham, Birmingham, UK. Electronic address: karen.mullinger@nottingham.ac.uk.
authors.forename: K J
authors.initials: KJ
authors.lastname: Mullinger
authors.affiliation: Birmingham University Imaging Centre, School of Psychology, University of Birmingham, Birmingham, UK.
authors.forename: S D
authors.initials: SD
authors.lastname: Mayhew
authors.affiliation: Birmingham University Imaging Centre, School of Psychology, University of Birmingham, Birmingham, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Bagshaw
authors.affiliation: Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK.
authors.forename: R
authors.initials: R
authors.lastname: Bowtell
authors.affiliation: Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK.
authors.forename: S T
authors.initials: ST
authors.lastname: Francis
mesh_terms: D000328:Adult; D000818:Animals; D001931:Brain Mapping / Q000379:methods*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004569:Electroencephalography / Q000379:methods*; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008475:Median Nerve / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D066191:Sensorimotor Cortex / Q000502:physiology*; D004561:Transcutaneous Electric Nerve Stimulation / Q000379:methods