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Functional MRI (fMRI) exploits a relationship between neuronal activity, metabolism, and cerebral blood flow to functionally map the brain. We have developed a model of direct cortical stimulation in the rat that can be combined with fMRI and used to compare the hemodynamic responses to direct and indirect cortical stimulation. Unilateral electrical stimulation of the rat hindpaw motor cortex, via stereotaxically positioned carbonfiber electrodes, yielded blood oxygenation level-dependent (BOLD) fMRI signal changes in both the stimulated and homotypic contralateral motor cortices. The maximal signal intensity change in both cortices was similar (stimulated ‫؍‬ 3.7 ؎ 1.7%; contralateral ‫؍‬ 3.2 ؎ 1.0%), although the response duration in the directly stimulated cortex was significantly longer ( Key words: magnetic resonance; fMRI; BOLD; cortical stimulation; transcallosal activation; rat Neuronal activation is accompanied by increases in local cerebral blood flow (CBF) and energy metabolism. This relationship has been exploited in functional MRI (fMRI) to allow mapping of "brain activation" using blood oxygenation level-dependent (BOLD) contrast (for reviews, see 1-3). BOLD fMRI is sensitive to changes in the concentration of deoxyhemoglobin, which decreases during neuronal activation due to a greater increase in CBF relative to the increase in the cerebral metabolic rate of oxygen (CMRO 2 ). While the mechanisms that underlie this neurovascular coupling are poorly understood, there has been increasing interest in making quantitative interpretation of the BOLD changes in relation to the underlying neuronal behavior.The cortex consists of a variety of neuronal cell types which have different electrophysiological properties (4). A major factor thought to influence activity-dependent increases in CBF is the energy-consuming process of membrane-potential restoration following synaptic activity. Thus, it may be expected that the constitution and extent of the neuronal pool activated would affect the BOLD response observed. Consistent with this notion, a study using Laser-Doppler Flowmetry (LDF) has demonstrated both a dependence of cerebral perfusion on stimulation amplitude and frequency and differential CBF increases in the different cortical layers of the rat somatosensory cortex to electrical stimulation of the infraorbital nerve (5). Akgoren et al. (6) demonstrated that even for the same target cell, the amplitude and mechanism of activity-dependent CBF increase might vary, depending on the synaptic region stimulated. Such differences may be accompanied by different concentrations and regional distributions of the various mediators of neurovascular coupling that are released during neuronal stimulation, including adenosine and nitric oxide (7).Rodent fMRI studies to date have been dominated by the forepaw stimulation model, in which a nonnoxious electrical stimulation is applied to the forepaw and activation is observed in the contralateral somatosensory cortex (8 -10). Although this has provided a standardized t...