It is not currently known whether subjects can learn to voluntarily control activation in localized regions of their own brain using neuroimaging. Here, we show that subjects were able to learn enhanced voluntary control over task-specific activation in a chosen target region, the somatomotor cortex. During an imagined manual action task, subjects were provided with continuous direction regarding their cognitive processes. Subjects received feedback information about their current level of activation in a target region of interest (ROI) derived using real-time functional magnetic resonance imaging (rtfMRI), and they received automatically-adjusted instructions for the level of activation to achieve. Information was provided both as continously upated graphs and using a simple virtual reality interface that provided an image analog of the level of activation. Through training, subjects achieved an enhancement in their control over brain activation that was anatomically specific to the target ROI, the somatomotor cortex. The enhancement took place when rtfMRI-based training was provided, but not in a control group that received similar training without rtfMRI information, showing that the effect was not due to conventional, practice-based neural plasticity alone. Following training, using cognitive processes alone subjects could volitionally induce fMRI activation in the somatomotor cortex that was comparable in magnitude to the activation observed during actual movement. The trained subjects increased fMRI activation without muscle tensing, and were able to continue to control brain activation even when real-time fMRI information was no longer provided. These results show that rtfMRI information can be used to direct cognitive processes, and that subjects are able to learn volitionally regulate activation in an anatomically-targeted brain region, surpassing the task-driven activation present before training.