Global signal modulation of single-trial fMRI response variability: Effect on positive vs negative BOLD response relationship

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

doi:10.1016/j.neuroimage.2016.02.077

Abstract

In functional magnetic resonance imaging (fMRI), the relationship between positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to stimulation is potentially informative about the balance of excitatory and inhibitory brain responses in sensory cortex. In this study, we performed three separate experiments delivering visual, motor or somatosensory stimulation unilaterally, to one side of the sensory field, to induce PBR and NBR in opposite brain hemispheres. We then assessed the relationship between the evoked amplitudes of contralateral PBR and ipsilateral NBR at the level of both single-trial and average responses. We measure single-trial PBR and NBR peak amplitudes from individual time-courses, and show that they were positively correlated in all experiments. In contrast, in the average response across trials the absolute magnitudes of both PBR and NBR increased with increasing stimulus intensity, resulting in a negative correlation between mean response amplitudes. Subsequent analysis showed that the amplitude of single-trial PBR was positively correlated with the BOLD response across all grey-matter voxels and was not specifically related to the ipsilateral sensory cortical response. We demonstrate that the global component of this single-trial response modulation could be fully explained by voxel-wise vascular reactivity, the BOLD signal standard deviation measured in a separate resting-state scan (resting state fluctuation amplitude, RSFA). However, bilateral positive correlation between PBR and NBR regions remained. We further report that modulations in the global brain fMRI signal cannot fully account for this positive PBR–NBR coupling and conclude that the local sensory network response reflects a combination of superimposed vascular and neuronal signals. More detailed quantification of physiological and noise contributions to the BOLD signal is required to fully understand the trial-by-trial PBR and NBR relationship compared with that of average responses.

Highlights

BOLD functional magnetic resonance imaging is widely used in human neuroimaging to localise the spatial origin of brain activity in response to experimental tasks or stimuli
The group conjunction regions of interest (ROI) show that significant contralateral PCBF and ipsilateral NCBF responses were observed in primary somatosensory cortex and that these were highly comparable to the regions exhibiting positive BOLD responses (PBRs) and negative BOLD responses (NBRs) (Fig. 2C)
We focus our investigation on the relationship between contralateral PBR and ipsilateral NBR response regions as a marker of the balance of functional activity between directly stimulated and unstimulated sensory network regions, as there is a reasonable body of evidence to suggest that the ipsilateral NBR doesn't arise from purely vascular origins and may reflect cortical inhibition

Summary

Introduction

BOLD functional magnetic resonance imaging (fMRI) is widely used in human neuroimaging to localise the spatial origin of brain activity in response to experimental tasks or stimuli. BOLD response, PBR) to infer that increased neuronal activity occurred in response to the stimulus. This assumption is supported by neurophysiology experiments in both humans and primates which have shown that the fMRI signal is an indirect, vascular correlate of increased neuronal activity in the form of local field potential and multi-unit activity (Heeger et al, 2000; Logothetis et al, 2001; Magri et al, 2012; Mukamel et al, 2005; Viswanathan and Freeman, 2007).

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