What We Know and Do Not Know about the Functions of the Orbitofrontal Cortex after 20 Years of Cross-Species Studies

Neural responses in both rat and human OFC during reversal learning signal expectations of a subsequent reward outcome. A, Illustration of generic discrimination reversal task in which the subject is presented with two stimuli and on each trial gets to choose one. One of the stimuli, if chosen, yields a reward (illustrated here as the cherries), whereas the other stimulus yields either an aversive outcome or simply the absence of reward (no cherries). During the acquisition phase, the subject learns to discriminate between the two stimuli, choosing the stimulus associated with reward and avoiding the nonrewarding stimulus. After subjects have reached a criterion (typically after choosing the rewarded stimulus on a number of consecutive trials), a reversal phase ensues, during which the previously rewarded stimulus now yields nonreward, and the previously unrewarded stimulus now yields a reward outcome. Reversals can occur multiple times during task performance. B, Plot of spiking activity recorded extracellularly from a neuron in rat OFC during learning and reversal of an odor discrimination problem. One odor predicted availability of sucrose at a nearby well, whereas a second odor predicted quinine. Data are shown during and after learning (precriterion vs postcriterion) and after reversal. Each raster display shows neural activity time locked to odor onset. Gray shading shows odor sampling, and green or red shading indicates response to the fluid well, which was followed by delivery of sucrose or quinine at the end of the shaded region. Average activity is summarized in the perievent time histogram below each raster. This neuron exhibits elevated activity to sucrose and also during the delay in anticipation of sucrose during learning. After learning, the neuron also becomes active during sampling of odor 1, the sucrose-predicting odor cue. After reversal, the activity of the neuron tracks the sucrose outcome, rapidly changing to fire in anticipation of sucrose on odor 2 trials and slightly later during becoming active during actual sampling of odor 2. Data are from Stalnaker et al. (2007). C, Statistical map of BOLD responses from a functional magnetic resonance imaging study of reversal learning in humans (left), depicting activity in medial orbitofrontal cortex (circled). This image is from an analysis to detect areas correlating with expected reward in the interval between cue presentation and outcome delivery. Activity in medial OFC and adjacent medial prefrontal cortex is approximately linear with respect to the expected value of the outcome, as indicated by the plot of activity in this region against expected value derived from a computational model. Other areas showing significant effects in this analysis include the amygdala and anterior hippocampus bilaterally. Color bars depict t-statistic level. Errors bar depict SEM. Data are from Hampton et al. (2006).