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.


CONCLUSIONS
The role of the substantia nigra (SN) and ventral tegmental area (VTA) in appetitive learning is well established, but less is known about their contribution to aversive compared with appetitive learning, especially in humans. We used high-resolution fMRI to measure activity in the SN and VTA while participants underwent higher-order Pavlovian learning. We found a regional specialization within the SN: a ventromedial area was selectively engaged during appetitive learning, and a dorsolateral area during aversive learning. Activity in these areas predicted affective reactions to appetitive and aversive conditioned stimuli over 1 year later. 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.
Division of Humanities and Social Sciences and Computation and Neural Systems Program, California Institute of Technology, Pasadena, California 91125, pauli@caltech.edu.
Wolfgang M
WM
Pauli
Division of Humanities and Social Sciences and Computation and Neural Systems Program, California Institute of Technology, Pasadena, California 91125.
Tobias
T
Larsen
Division of Humanities and Social Sciences and Computation and Neural Systems Program, California Institute of Technology, Pasadena, California 91125.
Sven
S
Collette
Division of Humanities and Social Sciences and Computation and Neural Systems Program, California Institute of Technology, Pasadena, California 91125.
Julian M
http://orcid.org/0000-0001-9342-9014
JM
Tyszka
Department of Engineering, University of Cambridge, Cambridge CB2 1PZ, United Kingdom, and National Institute for Information and Communications Technology, Osaka, 565-0871, Japan.
Ben
B
Seymour
Division of Humanities and Social Sciences and Computation and Neural Systems Program, California Institute of Technology, Pasadena, California 91125.
John P
JP
O'Doherty
D000328:Adult; D001066:Appetite / Q000502:physiology*; D001362:Avoidance Learning / Q000502:physiology*; D001767:Blinking / Q000502:physiology; D003198:Computer Simulation; D003214:Conditioning, Classical / Q000502:physiology; D004644:Emotions; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008954:Models, Biological; D009038:Motion; D009415:Nerve Net / Q000502:physiology; D010100:Oxygen / Q000097:blood; D011680:Pupil / Q000502:physiology; D012119:Respiration; D013378:Substantia Nigra / Q000033:anatomy & histology* / Q000098:blood supply / Q000502:physiology*; D013649:Taste / Q000502:physiology; D055815:Young Adult
D010100:Oxygen
appetitive learning; aversive learning; brainstem; dopaminergic midbrain; fMRI