Source of nonlinearity of the BOLD response revealed by simultaneous fMRI and NIRS

The nonlinearity of the blood oxygenation level-dependent (BOLD) response to stimuli of different duration, particularly those of short duration, has been well studied by functional magnetic resonance imaging (fMRI). This nonlinearity is assumed to be due to neural adaptation and the nonlinearity of the response in the oxygen extraction fraction (OEF); the latter has not been examined quantitatively in humans. To evaluate how the OEF response contributes to the nonlinearity of the BOLD response to neural activity, we used simultaneous fMRI and near-infrared spectroscopy (NIRS). The responses to visual stimuli of four different durations were measured as changes in the BOLD signal and the NIRS-derived hemoglobin concentrations. The hemodynamic response nonlinearity was quantified using an impulse response function model with saturation nonlinearity scaling in the response amplitude, assuming that the unknown neural adaptation parameters varied within a physiologically feasible range. Independent of the degree of neural adaptation, the BOLD response consistently showed saturation nonlinearity similar to that of the OEF response estimated from the NIRS measures, the nonlinearity of which was greater than that of the response in the total hemoglobin concentration representing the cerebral blood volume (CBV). We also found that the contribution of the OEF response to the BOLD response was four to seven times greater than the contribution of the CBV response. Thus, we conclude that the nonlinearity of the BOLD response to neural activity originates mainly from that of the OEF response.