title: Representation of aversive prediction errors in the human periaqueductal gray.
abstract: Pain is a primary driver of learning and motivated action. It is also a target of learning, as nociceptive brain responses are shaped by learning processes. We combined an instrumental pain avoidance task with an axiomatic approach to assessing fMRI signals related to prediction errors (PEs), which drive reinforcement-based learning. We found that pain PEs were encoded in the periaqueductal gray (PAG), a structure important for pain control and learning in animal models. Axiomatic tests combined with dynamic causal modeling suggested that ventromedial prefrontal cortex, supported by putamen, provides an expected value-related input to the PAG, which then conveys PE signals to prefrontal regions important for behavioral regulation, including orbitofrontal, anterior mid-cingulate and dorsomedial prefrontal cortices. Thus, pain-related learning involves distinct neural circuitry, with implications for behavior and pain dynamics.
authors.affiliation: 1] Department of Psychology and Neuroscience, University of Colorado, Boulder, Boulder, Colorado, USA. [2] PERFORM Centre, Concordia University, Montreal, Quebec, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Roy
authors.affiliation: Department of Psychology, Columbia University, New York, New York, USA.
authors.forename: Daphna
authors.initials: D
authors.lastname: Shohamy
authors.affiliation: Center for Neural Science, New York University, New York, New York, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Daw
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado, Boulder, Boulder, Colorado, USA.
authors.forename: Marieke
authors.initials: M
authors.lastname: Jepma
authors.affiliation: 1] Department of Psychology, Columbia University, New York, New York, USA. [2] Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: G Elliott
authors.identifier: 000000022227119X
authors.initials: GE
authors.lastname: Wimmer
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado, Boulder, Boulder, Colorado, USA.
authors.forename: Tor D
authors.initials: TD
authors.lastname: Wager
mesh_terms: D000293:Adolescent; D000328:Adult; D001519:Behavior / Q000502:physiology; D001931:Brain Mapping; D005260:Female; D006179:Gyrus Cinguli / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D007858:Learning / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D010146:Pain / Q000503:physiopathology*; D059408:Pain Management; D010487:Periaqueductal Gray / Q000502:physiology* / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000502:physiology* / Q000503:physiopathology; D012054:Reinforcement, Psychology; D055815:Young Adult