LAUSR

Significance Recent studies have confirmed the role of dopamine firing in reward prediction error, even under perceptual uncertainty. However, little is known about dopamine behavior during the use of working memory or its role in motivation to work for reward. Here, we investigated these issues in a discrimination task. Fast dopamine responses reflected a perceptual bias while remaining consistent with the reward prediction error hypothesis. When the bias increased task difficulty, motivation positively correlated with both performance and dopamine activity. In addition, dopamine slowly ramped up in a motivation-dependent way during the working memory period. Characterizing dopamine neurons’ activity during tasks in which motivation influences behavior could importantly advance our knowledge of dopamine roles in effortful control. Little is known about how dopamine (DA) neuron firing rates behave in cognitively demanding decision-making tasks. Here, we investigated midbrain DA activity in monkeys performing a discrimination task in which the animal had to use working memory (WM) to report which of two sequentially applied vibrotactile stimuli had the higher frequency. We found that perception was altered by an internal bias, likely generated by deterioration of the representation of the first frequency during the WM period. This bias greatly controlled the DA phasic response during the two stimulation periods, confirming that DA reward prediction errors reflected stimulus perception. In contrast, tonic dopamine activity during WM was not affected by the bias and did not encode the stored frequency. More interestingly, both delay-period activity and phasic responses before the second stimulus negatively correlated with reaction times of the animals after the trial start cue and thus represented motivated behavior on a trial-by-trial basis. During WM, this motivation signal underwent a ramp-like increase. At the same time, motivation positively correlated with accuracy, especially in difficult trials, probably by decreasing the effect of the bias. Overall, our results indicate that DA activity, in addition to encoding reward prediction errors, could at the same time be involved in motivation and WM. In particular, the ramping activity during the delay period suggests a possible DA role in stabilizing sustained cortical activity, hypothetically by increasing the gain communicated to prefrontal neurons in a motivation-dependent way.