The nucleus accumbens and medial frontal cortex (MFC) are part of a loop involved in modulating behavior according to anticipated rewards. However, the precise temporal landscape of their electrophysiological interactions in humans remains unknown because it is not possible to record neural activity from the nucleus accumbens using noninvasive techniques. We recorded electrophysiological activity simultaneously from the nucleus accumbens and cortex (via surface EEG) in humans who had electrodes implanted as part of deep-brain-stimulation treatment for obsessive–compulsive disorder. Patients performed a simple reward motivation task previously shown to activate the ventral striatum. Spectral Granger causality analyses were applied to dissociate “top–down” (cortex → nucleus accumbens)- from “bottom–up” (nucleus accumbens → cortex)-directed synchronization (functional connectivity). “Top–down”-directed synchrony from cortex to nucleus accumbens was maximal over medial frontal sites and was significantly stronger when rewards were anticipated. These findings provide direct electrophysiological evidence for a role of the MFC in modulating nucleus accumbens reward-related processing and may be relevant to understanding the mechanisms of deep-brain stimulation and its beneficial effects on psychiatric conditions. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.