Dissociable Learning Processes Underlie Human Pain Conditioning

• Published in: Current biology Vol. 26; no. 1; pp. 52 - 58
• Main Authors: Zhang, Suyi, Mano, Hiroaki, Ganesh, Gowrishankar, Robbins, Trevor, Seymour, Ben
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 11.01.2016; Cell Press
• Subjects: Adult; Amygdala - physiology; Association Learning - physiology; Avoidance Learning - physiology; Brain - physiology; Cerebellum - physiology; Conditioning (Psychology) - physiology; Conditioning, Classical - physiology; Cues; Fear - physiology; Female; Humans; Magnetic Resonance Imaging; Male; Pain - physiopathology; Pain - psychology; Ventral Striatum - physiology
• ISSN: 0960-9822; 1879-0445; 1879-0445
• DOI: 10.1016/j.cub.2015.10.066

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. •Different brain learning systems are associated with different defensive responses•Cerebellar responses correlate with “associability” for ipsilateral predicted pain•The overall phenotype of conditioned pain is the sum of two part-independent processes The classical “fear” response elicited by the brain in the presence of threat is critical for survival. Using pain as the threat, Zhang et al. show that autonomic and motor defensive reactions are associated with multiple learning systems. This means the overall phenotype of pain-based fear response is the sum of partially independent processes.