Theoretical study of BOLD response to sinusoidal input.

This is a theoretical study of a compelling model of blood oxygen level-dependent (BOLD) response dynamics, measured in functional magnetic resonance imaging (fMRI). The novelty of this study involves the way the model is driven sinusoidally, in order to avoid onset and offset transients that pose difficulties in data analysis and interpretation. The driving frequency ranges over the natural time scales of the hemodynamic response (0.01-1 Hz), which also corresponds to the period in typical boxcar stimulus designs. At low stimulus amplitude, the predicted BOLD response is quasi-linear. The amplitude exhibits a mild peak near the modulation frequency 0.1 Hz, and falls rapidly for higher frequencies. The phase lag relative to the stimulus is a monotonically increasing function of the modulation frequency. These findings illustrate the dynamical nature of the BOLD response, and could be used to optimize experimental designs that admit sinusoidal modulation. Higher stimulus amplitude elicits nonlinear behavior characterized by a double peak during the positive deflection of the BOLD response. This finding is particularly interesting, because similar double peaks are seen frequently in BOLD data.