Distinct Contributions of Ventromedial and Dorsolateral Subregions of the Human Substantia Nigra to Appetitive and Aversive Learning
The role of neurons in the substantia nigra (SN) and ventral tegmental area (VTA) of the midbrain in contributing to the elicitation of reward prediction errors during appetitive learning has been well established. Less is known about the differential contribution of these midbrain regions to appetitive versus aversive learning, especially in humans. Here we scanned human participants with high-resolution fMRI focused on the SN and VTA while they participated in a sequential Pavlovian conditioning paradigm involving an appetitive outcome (a pleasant juice), as well as an aversive outcome (an unpleasant bitter and salty flavor). We found a degree of regional specialization within the SN: Whereas a region of ventromedial SN correlated with a temporal difference reward prediction error during appetitive Pavlovian learning, a dorsolateral area correlated instead with an aversive expected value signal in response to the most distal cue, and to a reward prediction error in response to the most proximal cue to the aversive outcome. Furthermore, participants' affective reactions to both the appetitive and aversive conditioned stimuli more than 1 year after the fMRI experiment was conducted correlated with activation in the ventromedial and dorsolateral SN obtained during the experiment, respectively. These findings suggest that, whereas the human ventromedial SN contributes to long-term learning about rewards, the dorsolateral SN may be particularly important for long-term learning in aversive contexts.
© 2015 the authors. Beginning six months after publication the Work will be made freely available to the public on SfN's website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/). Received June 13, 2015. Revision received August 17, 2015. Accepted September 8, 2015. This work was supported by the National Institute of Mental Health Caltech Conte Center for the Neurobiology of Social Decision Making. We thank all members of the O'Doherty Human Reward and Decision Making laboratory for help with preprocessing, statistical analysis of pupillometry and fMRI data, and helpful discussions. Author contributions: W.M.P., T.L., B.S., and J.P.O. designed research; W.M.P. and T.L. performed research; W.M.P. and J.M.T. contributed unpublished reagents/analytic tools; W.M.P., T.L., and S.C. analyzed data; W.M.P. and J.P.O. wrote the paper. The authors declare no competing financial interests.
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