Evidence that the negative BOLD response is neuronal in origin: A simultaneous EEG–BOLD–CBF study in humans

K.J Mullinger,S.D Mayhew,A.P Bagshaw,R Bowtell,S.T Francis

doi:10.1016/j.neuroimage.2014.02.029

K.J Mullinger, S.D Mayhew + Show 3 more

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https://doi.org/10.1016/j.neuroimage.2014.02.029

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Journal: NeuroImage	Publication Date: Mar 12, 2014
Citations: 128	License type: cc-by

Affiliation: University of Birmingham, University of Nottingham

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 10s 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 8–13Hz 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.

Highlights

Blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging is widely used for non-invasive measurement of the spatial location and intensity of human brain activity
By using simultaneous EEG–BOLD–cerebral blood flow (CBF) recordings in humans we advance the understanding of the origin of the negative BOLD response and its relationship with concurrent measurements of cerebral oxygen metabolism and neuronal activity
We observed spatially coincident negative BOLD and CBF responses in S1/M1 regions of the cortical hemisphere ipsilateral to median nerve stimulation (MNS) and the amplitude of these ipsilateral S1/M1 responses was negatively correlated with the amplitude of both somatosensory evoked potentials (SEPs) and induced mu-power EEG responses (Supplementary Fig. S1)

Summary

Introduction

Blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used for non-invasive measurement of the spatial location and intensity of human brain activity. An increase in neuronal activity in response to stimulation results in a local increase in blood oxygenation and a corresponding increase in BOLD signal (i.e. a positive BOLD response (PBR)) relative to the prestimulus baseline period (Ogawa et al, 1990). The PBR amplitude has been shown to correlate most strongly with increases in local field potential (LFP) measurements of neuronal activity (Logothetis et al, 2001; Magri et al, 2012; Viswanathan and Freeman, 2007). A decrease in BOLD signal below pre-stimulus baseline levels is termed a negative BOLD response (NBR).

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