A ventral striatal prediction error signal in human fear extinction learning

Animal studies have shown that the prediction error (PE) signal that drives fear extinction learning is encoded by phasic activity of midbrain dopamine (DA) neurons. Thus, the extinction PE resembles the appetitive PE that drives reward learning. In humans, fear extinction learning is less well understood. Using computational neuroimaging, a previous study from our group reported hemodynamic activity in the left ventral putamen, a subregion of the ventral striatum (VS), to correlate with a PE function derived from a formal associative learning model. The activity was modulated by genetic variation in a DA-related gene. To conceptually replicate and extend this finding, we here asked whether an extinction PE (EPE) signal in the left ventral putamen can also be observed when genotype information is not taken into account. Using an optimized experimental design for model estimation, we again observed EPE-related activity in the same striatal region, indicating that activation of this region is a feature of human extinction learning. We further observed significant EPE signals across wider parts of the VS as well as in frontal cortical areas. These results may suggest that the prediction errors during extinction learning are available to larger parts of the brain, as has also been observed in human neuroimaging studies of reward PE signaling. Conclusive evidence that the human EPE signal is of DAergic nature is still outstanding.