title: Dissociable Learning Processes Underlie Human Pain Conditioning.
abstract: Pavlovian conditioning underlies many aspects of pain behavior, including fear and threat detection [1], escape and avoidance learning [2], and endogenous analgesia [3]. Although a central role for the amygdala is well established [4], both human and animal studies implicate other brain regions in learning, notably ventral striatum and cerebellum [5]. It remains unclear whether these regions make different contributions to a single aversive learning process or represent independent learning mechanisms that interact to generate the expression of pain-related behavior. We designed a human parallel aversive conditioning paradigm in which different Pavlovian visual cues probabilistically predicted thermal pain primarily to either the left or right arm and studied the acquisition of conditioned Pavlovian responses using combined physiological recordings and fMRI. Using computational modeling based on reinforcement learning theory, we found that conditioning involves two distinct types of learning process. First, a non-specific "preparatory" system learns aversive facial expressions and autonomic responses such as skin conductance. The associated learning signals-the learned associability and prediction error-were correlated with fMRI brain responses in amygdala-striatal regions, corresponding to the classic aversive (fear) learning circuit. Second, a specific lateralized system learns "consummatory" limb-withdrawal responses, detectable with electromyography of the arm to which pain is predicted. Its related learned associability was correlated with responses in ipsilateral cerebellar cortex, suggesting a novel computational role for the cerebellum in pain. In conclusion, our results show that the overall phenotype of conditioned pain behavior depends on two dissociable reinforcement learning circuits.
authors.affiliation: Center for Information and Neural Networks, National Institute for Information and Communications Technology, 1-4 Yamadaoka, Suita, Osaka 565-0871, Japan; Computational and Biological Learning Laboratory, Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK. Electronic address: sz321@cam.ac.uk.
authors.forename: Suyi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Center for Information and Neural Networks, National Institute for Information and Communications Technology, 1-4 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mano
authors.affiliation: Center for Information and Neural Networks, National Institute for Information and Communications Technology, 1-4 Yamadaoka, Suita, Osaka 565-0871, Japan; CNRS-AIST JRL (Joint Robotics Laboratory), UMI3218/CRT, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8560, Japan.
authors.forename: Gowrishankar
authors.initials: G
authors.lastname: Ganesh
authors.affiliation: Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Downing Site, Cambridge CB2 3EB, UK.
authors.forename: Trevor
authors.initials: T
authors.lastname: Robbins
authors.affiliation: Center for Information and Neural Networks, National Institute for Information and Communications Technology, 1-4 Yamadaoka, Suita, Osaka 565-0871, Japan; Computational and Biological Learning Laboratory, Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK; Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Downing Site, Cambridge CB2 3EB, UK. Electronic address: bjs49@cam.ac.uk.
authors.forename: Ben
authors.initials: B
authors.lastname: Seymour
mesh_terms: D000328:Adult; D000679:Amygdala / Q000502:physiology; D001245:Association Learning / Q000502:physiology*; D001362:Avoidance Learning / Q000502:physiology*; D001921:Brain / Q000502:physiology; D002531:Cerebellum / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology*; D003463:Cues; D005239:Fear / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010146:Pain / Q000503:physiopathology* / Q000523:psychology; D066328:Ventral Striatum / Q000502:physiology