The average precue activity of positive neurons was higher on large-reward trials (Figures 3A and 4C; see also Figure S1A, arrow), while the average activity of negative neurons was higher on small-reward trials (Figures 3B and S1B). It was as if the VP neurons predicted the reward value DNA Damage inhibitor of the current trial even before the reward cue was presented. The prediction was possible because we used a pseudorandom reward schedule in which four consecutive trials consisted of two large-reward and two small-reward

trials. Thus, the monkeys could predict a large reward with a high probability in the next trial after they obtained a small reward and vice versa (Bromberg-Martin et al., 2010b). To test this issue, we compared VP neurons’ activity during the precue period (Figure S2). Thirteen out of 25 negative neurons and 11 out of 67 positive neurons showed significant differences in precue activity in reward-predictive manners (p < 0.05, Mann-Whitney U test). These results are consistent with the hypothesis that the VP neurons predicted the reward value

of the current trial based on the reward history. Animal’s reward expectation is known to influence saccadic performance (Takikawa et al., 2002; Watanabe et al., 2003). We hypothesized that VP neurons regulate the initiation of saccades using the reward expectation-related information. As a first step to test this hypothesis, we examined whether the activity of VP neurons was correlated with saccadic performance (i.e., saccade latency and velocity). We focused on the VP neurons’ activity during the presaccade period because it could directly modulate the saccadic preparatory PD-0332991 price signals in the oculomotor system. The presaccadic activity of VP neurons should then be correlated with the saccadic performance as it changed across trials. More specifically, since the position-reward contingency was reversed relatively frequently in our task, both VP presaccadic neuronal activity and saccadic performance should also be reversed in similar time courses. The results were basically consistent with this prediction (Figure 5). the Following the reversal of the position-reward contingency,

both saccade latency (Figure 5A) and saccade velocity (Figure 5B) showed clear changes. There were two kinds of reversal: small-to-large reversal (the saccade which had been associated with a small reward was now associated with a large reward) and large-to-small reversal (the saccade which had been associated with a large reward was now associated with a small reward). The saccade latency decreased and the saccade velocity increased instantly after the small-to-large reversal. In contrast, the saccade latency increased and the saccade velocity decreased more slowly after the large-to-small reversal. The presaccadic activity of VP neurons also changed clearly following the reversal of the position-reward contingency (Figures 5C and 5D).