L-DOPA and oxytocin influence the neurocomputational mechanisms of self-benefitting and prosocial reinforcement learning

Humans learn through reinforcement, particularly when outcomes are unexpected. Recent research suggests similar mechanisms drive how we learn to benefit other people, that is, how we learn to be prosocial. Yet the neurochemical mechanisms underlying such prosocial computations remain poorly understood. Here, we investigated whether pharmacological manipulation of oxytocin and dopamine influence the neurocomputational mechanisms underlying self-benefitting and prosocial reinforcement learning. Using a double-blind placebo-controlled cross-over design, we administered intranasal oxytocin (24 IU), dopamine precursor L-DOPA (100 mg + 25 mg carbidopa), or placebo over three sessions. Participants performed a probabilistic reinforcement learning task with potential rewards for themselves, another participant, or no one, during functional magnetic resonance imaging. Computational models of reinforcement learning were used to calculate prediction errors (PEs) and learning rates. Participants behavior was best explained by a model with different learning rates for each recipient, but these were unaffected by either drug. On the neural level, however, both drugs blunted PE signaling in the ventral striatum and led to negative signaling of PEs in the anterior mid-cingulate cortex, dorsolateral prefrontal cortex, inferior parietal gyrus, and precentral gyrus, compared to placebo, and regardless of recipient. Oxytocin (versus placebo) administration was additionally associated with opposing tracking of self-benefitting versus prosocial PEs in dorsal anterior cingulate cortex, insula and superior temporal gyrus. These findings suggest that both L-DOPA and oxytocin induce a context-independent shift from positive towards negative tracking of PEs during learning. Moreover, oxytocin may have opposing effects on PE signaling when learning to benefit oneself versus another. This is an original manuscript of an article published in NeuroImage on April 15, 2023, available online: https://doi.org/10.1016/j.neuroimage.2023.119983.