title: Global signal modulation of single-trial fMRI response variability: Effect on positive vs negative BOLD response relationship.
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.
authors.affiliation: Birmingham University Imaging Centre (BUIC), School of Psychology, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: s.d.mayhew@bham.ac.uk.
authors.forename: S D
authors.initials: SD
authors.lastname: Mayhew
authors.affiliation: Birmingham University Imaging Centre (BUIC), School of Psychology, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Mullinger
authors.affiliation: Arbeitsbereich Computational Cognitive Neuroscience, Department of Education and Psychology, Free University Berlin, Berlin, Germany; Center for Adaptive Rationality (ARC), Max-Planck-Institute for Human Development, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Ostwald
authors.affiliation: Laboratory of Electrophysiology for Translational Neuroscience (LET'S) - ISTC - CNR, Department of Neuroscience, Fatebenefratelli Hospital Isola Tiberina, Rome, Italy; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK; Department of Information Engineering,Università Politecnica delle Marche, Ancona, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Porcaro
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: Birmingham University Imaging Centre (BUIC), School of Psychology, University of Birmingham, Edgbaston, Birmingham B15 2TT, 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: S T
authors.initials: ST
authors.lastname: Francis
mesh_terms: D000328:Adult; D001931:Brain Mapping / Q000379:methods*; D003198:Computer Simulation; D005073:Evoked Potentials, Somatosensory / Q000502:physiology*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008959:Models, Neurological; D015233:Models, Statistical; D015203:Reproducibility of Results; D018401:Sample Size; D012680:Sensitivity and Specificity; D013003:Somatosensory Cortex / Q000502:physiology*
keywords: Deactivation; Global signal; Negative BOLD response; RSFA