Certain classes of stimuli, such as food and drugs, are highly effective in
activating reward regions. We show in humans that activity in these region
s can be modulated by the predictability of the sequenced delivery of two m
ildly pleasurable stimuli, orally delivered fruit juice and water. Using fu
nctional magnetic resonance imaging, the activity for rewarding stimuli in
both the nucleus accumbens and medial orbitofrontal cortex was greatest whe
n the stimuli were unpredictable. Moreover, the subjects' stated preference
for either juice or water was not directly correlated with activity in rew
ard regions but instead was correlated with activity in sensorimotor cortex
. For pleasurable stimuli, these findings suggest that predictability modul
ates the response of human reward regions, and subjective preference can be
dissociated from this response.