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The Journal of Neuroscience, March 25, 2009, 29(12):3695-3704; doi:10.1523/JNEUROSCI.5195-08.2009

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Behavioral/Systems/Cognitive
Dopamine DRD2 Polymorphism Alters Reversal Learning and Associated Neural Activity

Gerhard Jocham,¹ Tilmann A. Klein,¹ Jane Neumann,² D. Yves von Cramon,^1,2 Martin Reuter,³ and Markus Ullsperger¹

¹Cognitive Neurology Research Group, Max Planck Institute for Neurological Research, D-50931 Cologne, Germany, ²Department of Cognitive Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, D-04103 Leipzig, Germany, and ³Department of Psychology, Laboratory of Neurogenetics, University of Bonn, D-53111 Bonn, Germany

Correspondence should be addressed to Gerhard Jocham, Cognitive Neurology Research Group, Max Planck Institute for Neurological Research, Gleueler Strasse 50, D-50931 Cologne, Germany. Email: jocham{at}nf.mpg.de

In humans, presence of an A1 allele of the DRD2/ANKK1-TaqIa polymorphism is associated with reduced expression of dopamine (DA) D₂ receptors in the striatum. Recently, it was observed that carriers of the A1 allele (A1+ subjects) showed impaired learning from negative feedback in a reinforcement learning task. Here, using functional MRI (fMRI), we investigated carriers and noncarriers of the A1 allele while they performed a probabilistic reversal learning task. A1+ subjects showed subtle deficits in reversal learning. In particular, these deficits consisted of an impairment in sustaining the newly rewarded response after a reversal and in a generally decreased tendency to stick with a rewarded response. Both genetic groups showed increased fMRI signal in response to negative feedback in the rostral cingulate zone (RCZ) and anterior insula. Negative feedback that incurred a change in behavior additionally engaged the ventral striatum and a region of the midbrain consistent with the location of dopaminergic cell groups. The response of the RCZ to negative feedback increased as a function of preceding negative feedback. However, this graded response was not observed in the A1+ group. Furthermore, the A1+ group also showed diminished recruitment of the right ventral striatum and the right lateral orbitofrontal cortex (lOFC) during reversals. Together, these results suggest that a genetically driven reduction in DA D₂ receptors leads to deficient feedback integration in RCZ. This, in turn, was accompanied by impaired recruitment of the ventral striatum and the right lOFC during reversals, which might explain the behavioral differences between the genetic groups.

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Received Oct. 28, 2008; revised Nov. 26, 2008; accepted Jan. 26, 2009.

Correspondence should be addressed to Gerhard Jocham, Cognitive Neurology Research Group, Max Planck Institute for Neurological Research, Gleueler Strasse 50, D-50931 Cologne, Germany. Email: jocham{at}nf.mpg.de

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				D. G. Ghahremani, J. Monterosso, J. D. Jentsch, R. M. Bilder, and R. A. Poldrack Neural Components Underlying Behavioral Flexibility in Human Reversal Learning Cereb Cortex, November 13, 2009; (2009) bhp247v1. [Abstract] [Full Text] [PDF]

				G. Jocham, J. Neumann, T. A. Klein, C. Danielmeier, and M. Ullsperger Adaptive Coding of Action Values in the Human Rostral Cingulate Zone J. Neurosci., June 10, 2009; 29(23): 7489 - 7496. [Abstract] [Full Text] [PDF]

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