Poststimulus undershoots in cerebral blood flow and BOLD fMRI responses are modulated by poststimulus neuronal activity.

fMRI is the foremost technique for noninvasive measurement of human brain function. However, its utility is limited by an incomplete understanding of the relationship between neuronal activity and the hemodynamic response. Though the primary peak of the hemodynamic response is modulated by neuronal activity, the origin of the typically negative poststimulus signal is poorly understood and its amplitude assumed to covary with the primary response. We use simultaneous recordings of EEG with blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF) fMRI during unilateral median nerve stimulation to show that the poststimulus fMRI signal is neuronally modulated. We observe high spatial agreement between concurrent BOLD and CBF responses to median nerve stimulation, with primary signal increases in contralateral sensorimotor cortex and primary signal decreases in ipsilateral sensorimotor cortex. During the poststimulus period, the amplitude and directionality (positive/negative) of the BOLD signal in both contralateral and ipsilateral sensorimotor cortex depends on the poststimulus synchrony of 8-13 Hz EEG neuronal activity, which is often considered to reflect cortical inhibition, along with concordant changes in CBF and metabolism. Therefore we present conclusive evidence that the fMRI time course represents a hemodynamic signature of at least two distinct temporal phases of neuronal activity, substantially improving understanding of the origin of the BOLD response and increasing the potential measurements of brain function provided by fMRI. We suggest that the poststimulus EEG and fMRI responses may be required for the resetting of the entire sensory network to enable a return to resting-state activity levels.