The present report therefore demonstrates the first unambiguous evidence for a stimulus-selective reward signal in primate visual

cortex. Furthermore, in contrast to the selective enhancements that have been observed within attended stimulus representations without visual stimulation ( Kastner et al., 1999; Sylvester et al., 2007), we found a selective reduction of activity within the reward-paired cue representation. The opposite polarity of the reward modulations provides further evidence SNS-032 concentration that the modulations we observed are unlikely to result from attention. Hemodynamic activity in early visual cortex can display fluctuations that depend on trial structure and not reward (Sirotin and Das, 2009), or upon the timing of the expected reward, rather than the reward itself (Shuler and Bear, 2006, their Figure 4). In experiment 1, uncued reward activity was defined by contrasting uncued reward trials with fixation trials. Crucially, the uncued

reward indicated the end of the current trial and the beginning of the next randomized wait period, while no information about trial structure was available during fixation trials. Trial-structure-dependent fluctuations in attention, hazard-rate or anticipation could therefore account for reward modulations observed in the first experiment. Alternatively, fixation trials in which no reward is administered could be viewed by the monkey as a reward-omission trial, leaving a reward-omission signal as a potential source of buy Lapatinib the modulations recorded in experiment

1. To disambiguate this first set of results, we utilized a paradigm with two reward sizes, which conveyed the same trial structure information, in experiment 3. With trial-structure information held constant and reward omissions eliminated, we found significantly stronger deactivations within the cue-representation during larger uncued reward. These results confirm that uncued reward activity was dependent on the attributes of the reward and not on other factors Phosphoprotein phosphatase such as reward-omission or trial-structure. Manipulations of uncued reward size, cue-reward probabilities, and cue-reward familiarity have been shown to alter PE in monkeys and the subsequent responses of dopamine neurons (Schultz, 2006). For instance, large unpredicted reward have been shown to elicit stronger PE and larger PE responses from dopamine neurons than small reward (Tobler et al., 2005), exactly as we observed in the ventral midbrain (Experiment 3). Therefore, although we did not measure the monkey’s subjective predictions directly through anticipatory licking (Fiorillo et al., 2003), the use of known properties of PE and the responses of dopamine neurons provided a consistent description of the data acquired in all 7 experiments.