Encoding of predictive associations in human prefrontal and medial temporal neurons during Pavlovian appetitive conditioning

Pavlovian conditioning is thought to involve the formation of learned associations between stimuli and values, and between stimuli and specific features of outcomes. Here we leveraged human single neuron recordings in ventromedial prefrontal, dorsomedial frontal, hippocampus and amygdala while patients of both sexes performed an appetitive Pavlovian conditioning task probing both stimulus-value and stimulus-stimulus associations. Ventromedial prefrontal cortex encoded predictive value along with the amygdala, but also encoded predictions about the identity of stimuli that would subsequently be presented, suggesting a role for neurons in this region in encoding predictive information beyond value. Unsigned error signals were found in dorsomedial frontal areas and hippocampus, potentially supporting learning of non-value related outcome features. Our findings implicate distinct human prefrontal and medial temporal neuronal populations in mediating predictive associations which could partially support model-based mechanisms during Pavlovian conditioning.Significance statement In this study, epilepsy patients implanted intracranially with depth microelectrodes performed a Pavlovian conditioning task. We measured single neuron activity in ventromedial prefrontal cor-tex (vmPFC), amygdala, and hippocampus, and found a representation of predictive identity coding and Pavlovian expected reward values. Additionally, unsigned error signals were found in dorsomedial frontal areas as well as hippocampus. This study thus provides a rare glimpse into the role of frontal human neurons in predictive associative learning of values and stimulus identities.