Are the local hemodynamic changes in BOLD-fMRI correlated to increased or decreased neuronal activity or both? We combined transcranial electrical cortex stimulation (TES) with simultaneous fMRI and electromyographic (EMG) recording to study the influence of inhibitory and excitatory neuronal activity on the concomitant BOLD signal change. Unilateral or bilateral TES was applied with a postero-anterior orientation. This activates pyramidal cells transsynaptically and allows for the induction of cortical inhibition and excitation of the pyramidal cell, respectively. In this project interhemispheric inhibition (IHI) served as an in vivo model to investigate electrophysiologically well defined inhibitory and excitatory effects. MethodologyIncluded event-related fMRI, which triggered TES; online recording of the EMG response monitored the inhibitory and excitatory influences on discharging corticospinal neurons. ResultsRevealed that a single suprathreshold stimulus induced a positive BOLD response both in the ipsilateral as well as in the contralateral primary motor cortex (M1). The contralateral co-activation of the homotopic M1 should be a functional correlate of transcallosal connections. If a contralateral conditioning stimulus preceded the test stimulus by 10 ms (IHI), the subsequent ipsilateral BOLD signal was significantly reduced. We find that cortical inhibitory processes are accompanied by attenuation of the local neurovascular signal.