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One of the critical issues in brain-computer interface (BCI) research is how to translate a person's intention into brain signals for controlling computer programs. The motor system is currently the primary focus, where signals are obtained during imagined motor responses. However, cognitive brain systems are also attractive candidates, in that they may be more amenable to conscious control, yielding better regulation of magnitude and duration of localized brain activity. We report on a proof of principle study for the potential use of a higher cognitive system for BCI, namely the working memory (WM) system. We show that mental calculation reliably activates the WM network as measured with functional magnetic resonance imaging (fMRI). Moreover, activity in the dorsolateral prefrontal cortex (DLPFC) indicates that this region is active for the duration of mental processing. This supports the notion that DLPFC can be activated, and remains active, at will. Further confirmation is obtained from a patient with an implanted electrode grid for diagnostic purposes, in that gamma power within DLPFC increases during mental calculation and remains elevated for the duration thereof. These results indicate that cortical regions involved in higher cognitive functions may serve as a readily self-controllable input for BCI applications. It also shows that fMRI is an effective tool for identifying function-specific foci in individual subjects for subsequent placement of cortical electrodes. The fact that electrocorticographic (ECoG) signal confirmed the functional localization of fMRI provides a strong argument for incorporating fMRI in BCI research.