Embodiments of the present invention relate to systems and methods for calibrating functional magnetic resonance imaging of living tissue. For example, a calibration method includes providing a contrast signal simulation device configured for generating one or more pre-determined contrast simulation signals selected from a group consisting of BOLD and BOSS contrast simulation signals that simulate at least one contrast signal generated by living tissue of a subject and positioning the contrast signal simulation device adjacent to the subject. The method includes using an imaging instrument to take first and second data sets from the subject's tissue while the contrast signal simulation device is disposed adjacent to the subject and while generating and not generating the one or more pre-determined contrast simulation signals, respectively. The method also includes using the first and second data sets to determine at least one figure of merit of the imaging instrument, the contrast simulation device, and/or the living tissue.