Coupling of neural activity and BOLD fMRI response: New insights by combination of fMRI and VEP experiments in transition from single events to continuous stimulation

Abstract

Functional magnetic resonance imaging (fMRI) measures the correlation between the fMRI response and stimulus properties. A linear relationship between neural activity and fMRI response is commonly assumed. However, the response to repetitive stimulation cannot be explained by a simple superposition of singleevent responses. This might be due to neural adaptation or the hemodynamic changes underlying the fMRI BOLD response. To assess the influence of adaptation, the BOLD responses and visual evoked potentials (VEPs) to identical stimuli were recorded. To achieve different adaptation levels, 2-s stimulus epochs alter- In most functional magnetic resonance imaging (fMRI) experiments the correlation between the fMRI response and the application of a stimulus is measured. Although the nature of the complex interactions among the neurons, hemodynamic changes, and MRI is still unclear, it has been hypothesized that the fMRI response is a linear transformation of the neural activity averaged over time and voxel volume (1,2). At least for simple visual stimulation the model allows predictions of the observed blood oxygenation level dependent (BOLD) fMRI signal. While avoiding issues surrounding habituation effects by using single trials of fixed duration, sufficiently separated in time, it was shown that the BOLD fMRI response to multiple trials behaved approximately linearly (3-6). However, there is substantial literature (2,7-11) on nonlinear responses, and some disagreement on this point. Although there is evidence for neural adaptation in single cells (12) and evoked potentials (13,14), it is not clear whether the adaptation in fMRI is neural, hemodynamic, or a combination of both.The goal of this study was to evaluate if neural adaptation is sufficient to predict the observed nonlinearity in fMRI experiments. Therefore, identical visual stimulation paradigms were presented during fMRI as well as VEP recording to assess the influence of neural adaptation on the fMRI response. METHODS SubjectsTen healthy volunteers (four males and six females, 22-40 years old) participated in the VEP experiments, and eight healthy volunteers (six males and two females, 22-40 years old) in the fMRI experiments. Three of the subjects participated in both the VEP and fMRI experiments. All subjects provided informed consent, and the study was approved by the Institutional Review Board. Visual StimulationIn all experiments a phase-reversing checkerboard pattern served as the visual stimulus. The checkerboard was confined to a circular area of 25°diameter, checksize was 1.3°, contrast 96%, and reversal rate was 4.16 Hz ϭ 8.3 reversals/s. As the baseline condition between the stimulation units (ϭ in the interstimulus intervals (ISI)), spatially homogenous gray stimuli were displayed with identical net luminance.In the fMRI session the stimulation pattern was generated on a PowerMac and projected by video projector onto a backprojection screen in the magnet bore. The stimulation timing was 120 s stimulation with a fixed ISI and 60-s pause. Th...

Simultaneous recordings of visual evoked potentials and BOLD MRI activations in response to visual motion processing

“…In contrast to the marked VEP response to motion onset with a most pronounced N2 component, BOLD MRI activations were strongest for motion reversal which does not show an associated N2 component. This finding apparently contradicts studies reporting a linear positive correlation of BOLD MRI activations and evoked potentials in the somatosensory and visual system (36)(37)(38). On a much smaller scale, also local field potentials (LFPs) and BOLD MRI responses were found to be positively correlated (39).…”

BOLD Consistently Matches Electrophysiology in Human Sensorimotor Cortex at Increasing Movement Rates: A Combined 7T fMRI and ECoG Study on Neurovascular Coupling

“…Previous studies that have combined electrophysiology and BOLD or blood flow measurements have focused mainly on sensory cortices such as the visual or somatosensory cortex using passive neuronal stimulation, either invasively in rodents or primates, or non-invasively using scalp-based electrophysiology measurements electroencephalography (EEG) in humans. 5,[31][32][33][34][35][36][37] While nonlinearities in hemodynamic and electrophysiological measurements are often reported, two studies on human visual cortex using modulation of the stimulation frequency suggested that the hemodynamic response nonlinearity can potentially be explained by the nonlinear electrophysiological activity as captured by the EEG event-related potentials. 31,32 Electroencephalography measurements, however, do not allow for accurate localization of the source of electrophysiological responses because of the inverse problem.…”

Stimulus repetition and hemodynamic response refractoriness in event‐related fMRI

“…However, a significant component of the reduction in signal observed when different faces were presented sequentially may still be reasonably attributed to hemodynamic coupling or vascular effects. The importance of hemodynamic factors underlying reduced signal recovery is suggested by a study showing overestimation of the BOLD response even after weighting a linearly predicted fMRI response using simultaneous, empirically derived visual evoked responses to alternating checkerboards [Janz et al, 2001]. This study showed that hemodynamic effects occur in addition to neural habituation effects.…”