, 2003; Ljungberg et al., 1992; Matsumoto and Hikosaka, 2009), exhibit a phasic prediction error (PE) response signaling the difference between outcome and expectation (Bromberg-Martin et al., 2010; Schultz et al., 1997). Moreover, PE signals originating in ventral midbrain neurons are relayed through a widespread network of connections (Lidow et al., 1991; Lindvall et al., 1974), resulting in increased dopamine

release (Gonon, 1988; Zhang et al., 2009), activity modulation (Pessiglione et al., 2006), and plasticity (Surmeier et al., 2010) at projection sites. Accordingly, a recent human fMRI study has shown that reward information was present throughout most brain regions tested (Vickery et al., 2011). Therefore, the highly selective behavioral and neural effects induced by stimulus-reward pairings must be TGF-beta inhibitor reconciled with the apparent widespread and diffuse nature of neuromodulatory reward signals.

A potential explanation for this seeming contradiction is that selectivity arises through an interaction between a broadly distributed reward signal and coincident bottom-up, cue-driven activity. In this way, a diffuse dopaminergic reward signal is rendered selective, allowing reward to specifically modulate BKM120 in vivo activity within reward-predicting cue representations (Roelfsema et al., 2010; Seitz and Watanabe, 2005). In agreement with this interpretation, the pairing of an auditory stimulus with microstimulation of the ventral tegmental area (VTA), Mannose-binding protein-associated serine protease a surrogate for reward, specifically enhanced the representation of a stimulation-paired frequency within rat auditory cortex in a dopamine-dependent manner (Bao et al., 2001). In addition, Pleger et al. (2009) has found a stimulus-selective, dopaminergic

reward feedback signal within human somatosensory cortex. Surprisingly though, direct evidence for selective reward modulations in primate visual cortex has not yet been demonstrated. This is probably due to the difficulty of disentangling reward from other co-occurring cognitive factors such as attention (Maunsell, 2004). For example, while Serences (2008) found that the association of a visual stimulus with a higher reward probability resulted in stimulus-selective increases in fMRI activity, the contributions of reward and attention to these results are indistinguishable. Weil et al., (2010) also looked at the effects of direct stimulus-reward relationships in visual cortex. In an effort to isolate reward effects from attention, they temporally disassociated reward from stimulus presentation. This study, however, found only a main effect of reward outside the representation of the visual stimulus suggesting these reward modulations were stimulus aspecific. In order to differentiate the contributions of attention and reward, we developed a paradigm for investigating cue-selective reward modulations that were temporally separated from discrete cue-reward association trials.