To adjust expectations efficiently, prediction errors need to be associated with the precise features that gave rise to the unexpected outcome, but this credit assignment may be problematic if stimuli differ on multiple dimensions and it is ambiguous which feature dimension caused the outcome. Here, we report a potential solution: neurons in four recorded areas of the anterior fronto-striatal networks encode prediction errors that are specific to feature values of different dimensions of attended multidimensional stimuli. The most ubiquitous prediction error occurred for the reward-relevant dimension. Feature-specific prediction error signals a) emerge on average shortly after non-specific prediction error signals, b) arise earliest in the anterior cingulate cortex and later in dorsolateral prefrontal cortex, caudate and ventral striatum, and c) contribute to feature-based stimulus selection after learning. Thus, a widely-distributed feature-specific eligibility trace may be used to update synaptic weights for improved feature-based attention.

HighlightsNeural reward prediction errors carry information for updating feature-based attention in all areas of the fronto-striatal network.Feature specific neural prediction errors emerge earliest in anterior cingulate cortex and later in lateral prefrontal cortex.Ventral striatum neurons encode feature specific surprise strongest for the goal-relevant feature.Neurons encoding feature-specific prediction errors contribute to attentional selection after learning.

Nicotinic acetylcholine receptors (nAChR) modulate attention, memory, and higher executive functioning, but it has remained unclear whether nAChR sub-receptors tap into different neural mechanisms of these functions. We therefore set out to contrast the contributions of selective alpha-7 nAChR and alpha-4/beta-2 nAChR agonists in mediating value learning and attentional filtering of distractors in the nonhuman primate. We found that the alpha-7 nAChR agonist PHA-543613 selectively enhanced the learning speed of feature values but did not modulate how salient distracting information was filtered from ongoing choice processes. In contrast, the selective alpha-4/beta-2 nAChR agonist ABT-089 did not affect learning speed but reduced distractibility. This double dissociation was dose-dependent and evident in the absence of systematic changes in overall performance, reward intake, motivation to perform the task, perseveration tendencies, or reaction times. These results suggest nicotinic sub-receptor-specific mechanisms consistent with (1) alpha-4/beta-2 nAChR specific amplification of cholinergic transients in prefrontal cortex linked to enhanced cue detection in light of interferences, and (2) alpha-7 nAChR specific activation prolonging cholinergic transients, which could facilitate subjects to follow-through with newly established attentional strategies when outcome contingencies change. These insights will be critical for developing function-specific drugs alleviating attention and learning deficits in neuro-psychiatric diseases.

Nicotinic acetylcholine receptors (nAChR) modulate attention, memory, and higher executive functioning, but it has remained unclear whether nAChR sub-receptors tap into different neural mechanisms of these functions. We therefore set out to contrast the contributions of selective alpha-7 nAChR and alpha-4/beta-2 nAChR agonists in mediating value learning and attentional filtering of distractors in the nonhuman primate. We found that the alpha-7 nAChR agonist PHA-543613 selectively enhanced the learning speed of feature values but did not modulate how salient distracting information was filtered from ongoing choice processes. In contrast, the selective alpha-4/beta-2 nAChR agonist ABT-089 did not affect learning speed but reduced distractibility. This double dissociation was dose-dependent and evident in the absence of systematic changes in overall performance, reward intake, motivation to perform the task, perseveration tendencies, or reaction times. These results suggest nicotinic sub-receptor-specific mechanisms consistent with (1) alpha-4/beta-2 nAChR specific amplification of cholinergic transients in prefrontal cortex linked to enhanced cue detection in light of interferences, and (2) alpha-7 nAChR specific activation prolonging cholinergic transients, which could facilitate subjects to follow-through with newly established attentional strategies when outcome contingencies change. These insights will be critical for developing function-specific drugs alleviating attention and learning deficits in neuro-psychiatric diseases.