Periaqueductal gray matter and medial prefrontal cortex reflect negative prediction errors during differential conditioning.

Computational models of associative learning posit that negative prediction errors arising from the omission of aversive outcomes weaken aversive Pavlovian associations during differential conditioning and extinction. It is possible that negative prediction errors may underlie exaggerated conditioned responses to the CS- during differential conditioning and to the CS+ during extinction in patients with clinical anxiety disorders. Although previous research has demonstrated that manipulations of the periaqueductal gray matter (PAG) interfere with extinction learning in animals, the role of the PAG in processing negative prediction errors within the human brain is presently unclear. We set out to investigate how PAG BOLD responses and connectivity are impacted by negative prediction errors using ultra-high field (7T) functional MRI and hierarchical Bayesian analysis. During differential conditioning, negative prediction errors were associated with larger BOLD responses within the lateral and dorsolateral PAG and increased connectivity between the dorsolateral PAG and medial areas of Brodmann area 9. The relationship between negative prediction errors and BOLD responses during extinction was not significant. Collectively, these results shed light on the association between activity within the PAG and medial prefrontal cortex and the omission of aversive outcomes during Pavlovian learning.