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J Neurophysiol 92: 1144-1152, 2004. First published March 10, 2004; doi:10.1152/jn.01209.2003
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Human Midbrain Sensitivity to Cognitive Feedback and Uncertainty During Classification Learning

A. R. Aron1, D. Shohamy2, J. Clark3, C. Myers4, M. A. Gluck2 and R. A. Poldrack1,3

1Department of Psychology and Brain Research Institute, University of California, Los Angeles, California 90065; 2Center for Molecular and Behavioral Neuroscience and 4Department of Psychology, Rutgers University, New Brunswick, New Jersey 08903; and 3Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Massachusetts 02129

Submitted 15 December 2003; accepted in final form 6 March 2004

Mesencephalic dopaminergic system (MDS) neurons may participate in learning by providing a prediction error signal to their targets, which include ventral striatal, orbital, and medial frontal regions, as well as by showing sensitivity to the degree of uncertainty associated with individual stimuli. We investigated the mechanisms of probabilistic classification learning in humans using functional magnetic resonance imaging to examine the effects of feedback and uncertainty. The design was optimized for separating neural responses to stimulus, delay, and negative and positive feedback components. Compared with fixation, stimulus and feedback activated brain regions consistent with the MDS, whereas the delay period did not. Midbrain activity was significantly different for negative versus positive feedback (consistent with coding of the "prediction error") and was reliably correlated with the degree of uncertainty as well as with activity in MDS target regions. Purely cognitive feedback apparently engages the same regions as rewarding stimuli, consistent with a broader characterization of this network.


Address for reprint requests and other correspondence: R. A. Poldrack, Dept. of Psychology and Brain Research Institute, University of California, Los Angeles, CA 90065 (E-mail: poldrack{at}ucla.edu).




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