Recent advances in neurofeedback based on real-time functional magnetic resonance imaging (fMRI) allow for learning to control spatially localized brain activity in the range of millimeters across the entire brain. Realtime fMRI neurofeedback studies have demonstrated the feasibility of self-regulating activation in specific areas that are involved in a variety of functions, such as perception, motor control, language, and emotional processing. In most of these previous studies, participants trained to control activity within one region of interest (ROI). In the present study, we extended the neurofeedback approach by now training healthy participants to control the interhemispheric balance between their left and right visual cortices. This was accomplished by providing feedback based on the difference in activity between a target visual ROI and the corresponding homologue region in the opposite hemisphere. Eight out of 14 participants learned to control the differential feedback signal over the course of 3 neurofeedback training sessions spread over 3 days, i.e., they produced consistent increases in the visual target ROI relative to the opposite visual cortex. Those who learned to control the differential feedback signal were subsequently also able to exert that control in the absence of neurofeedback. Such learning to voluntarily control the balance between cortical areas of the two hemispheres might offer promising rehabilitation approaches for neurological or psychiatric conditions associated with pathological asymmetries in brain activity patterns, such as hemispatial neglect, dyslexia, or mood disorders. (C) 2014 Elsevier Inc. All rights reserved.