In this paper, we demonstrate an approach by which some evoked neuronal events can be probed by functional MRI (fMRI) signal with temporal resolution at the time scale of tens of milliseconds. The approach is based on the close relationship between neuronal electrical events and fMRI signal that is experimentally demonstrated in concurrent fMRI and electroencephalographic (EEG) studies conducted in a rat model with forepaw electrical stimulation. We observed a refractory period of neuronal origin in a two-stimuli paradigm: the first stimulation pulse suppressed the evoked activity in both EEG and fMRI signal responding to the subsequent stimulus for a period of several hundred milliseconds. When there was an apparent site-site interaction detected in the evoked EEG signal induced by two stimuli that were primarily targeted to activate two different sites in the brain, fMRI also displayed signal amplitude modulation because of the interactive event. With visual stimulation using two short pulses in the human brain, a similar refractory phenomenon was observed in activated fMRI signals in the primary visual cortex. In addition, for interstimulus intervals shorter than the known latency time of the evoked potential induced by the first stimulus (Ϸ100 ms) in the primary visual cortex of the human brain, the suppression was not present. Thus, by controlling the temporal relation of input tasks, it is possible to study temporal evolution of certain neural events at the time scale of their evoked electrical activity by noninvasive fMRI methodology. Since the introduction of functional magnetic resonance imaging (fMRI) of the human brain in early 1990s, this noninvasive functional neuro-imaging modality has rapidly gained a prominent position in systems level neuroscience research. The most commonly used fMRI approach relies on blood oxygen level dependent (BOLD) contrast (1), which detects changes in regional deoxyhemoglobin content induced by alterations in cerebral blood flow (CBF) and͞or oxygen consumption rate (CMRO 2 ) that accompany modulations in neuronal activity. It is also possible to image regional CBF changes directly by magnetic resonance imaging with a little more elaborate data acquisition schemes and to generate functional maps based on CBF alterations alone (2).The tight coupling between neural activation and changes in CBF and͞or CMRO 2 that forms the basis of fMRI has been shown to be present mostly under steady state conditions (3-6). Brinker et al. (7) have reported the presence of the tight and highly quantitative coupling between the EEG signal and BOLD signal in their rat model experiments under ␣-chloralose anesthesia, where the frequency of forepaw stimulation rate was varied under steady state conditions. In the cerebellum of anesthetized rats, the regional CBF increase was also shown to be proportional to the product of the frequency of stimulation and the strength of the evoked local field potential near a Purkenje cell (8). Based on such coupling, two parameters that characterize the fMRI ...

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