Linear and nonlinear relationships between visual stimuli, EEG and BOLD fMRI signals.

In the present study, the cascaded interactions between stimuli and neural and hemodynamic responses were modeled using linear systems. These models provided the theoretical hypotheses that were tested against the electroencephalography (EEG) and blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) data recorded from human subjects during prolonged periods of repeated visual stimuli with a variable setting of the inter-stimulus interval (ISI) and visual contrast. Our results suggest that (1) neural response is nonlinear only when ISI<0.2 s, (2) BOLD response is nonlinear with an exclusively vascular origin when 0.25<ISI<4.2 s, (3) vascular response nonlinearity reflects a refractory effect, rather than a ceiling effect, and (4) there is a strong linear relationship between the BOLD effect size and the integrated power of event-related synaptic current activity, after modeling and taking into account the vascular refractory effect. These conclusions offer important insights into the origins of BOLD nonlinearity and the nature of neurovascular coupling, and suggest an effective means to quantitatively interpret the BOLD signal in terms of neural activity. The validated cross-modal relationship between fMRI and EEG may provide a theoretical basis for the integration of these two modalities. Copyright 2010 Elsevier Inc. All rights reserved.