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Votinov M, Pripfl J, Windischberger C, et al. A functional polymorphism in the prodynorphin gene affects cognitive flexibility and brain activation during reversal learning. Front Behav Neurosci. 2015;9:172doi: 10.3389/fnbeh.2015.00172.
Votinov, M., Pripfl, J., Windischberger, C., Moser, E., Sailer, U., & Lamm, C. (2015). A functional polymorphism in the prodynorphin gene affects cognitive flexibility and brain activation during reversal learning. Frontiers in behavioral neuroscience, 9172. https://doi.org/10.3389/fnbeh.2015.00172
Votinov, Mikhail, et al. "A functional polymorphism in the prodynorphin gene affects cognitive flexibility and brain activation during reversal learning." Frontiers in behavioral neuroscience vol. 9 (2015): 172. doi: https://doi.org/10.3389/fnbeh.2015.00172
Votinov M, Pripfl J, Windischberger C, Moser E, Sailer U, Lamm C. A functional polymorphism in the prodynorphin gene affects cognitive flexibility and brain activation during reversal learning. Front Behav Neurosci. 2015 Jul 03;9:172. doi: 10.3389/fnbeh.2015.00172. eCollection 2015. PMID: 26190983; PMCID: PMC4490246.
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Front Behav Neurosci. 2015 Jul 03;9:172. doi: 10.3389/fnbeh.2015.00172. eCollection 2015.

A functional polymorphism in the prodynorphin gene affects cognitive flexibility and brain activation during reversal learning.

Frontiers in behavioral neuroscience

Mikhail Votinov, Juergen Pripfl, Christian Windischberger, Ewald Moser, Uta Sailer, Claus Lamm

Affiliations

  1. Social, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna Vienna, Austria ; Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University Aachen, Germany.
  2. Social, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna Vienna, Austria.
  3. MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna Vienna, Austria.
  4. Social, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna Vienna, Austria ; Department of Psychology, University of Gothenburg Gothenburg, Sweden.

PMID: 26190983 PMCID: PMC4490246 DOI: 10.3389/fnbeh.2015.00172

Abstract

Whether the opioid system plays a role in the ability to flexibly adapt behavior is still unclear. We used fMRI to investigate the effect of a nucleotide tandem repeat (68-bp VNTR) functional polymorphism of the prodynorphin (PDYN) gene on cerebral activation during a reversal learning task in which participants had to flexibly adapt stimulus-response associations. Past studies suggested that alleles with 3 or 4 repeats (HH genotype) of this polymorphism are associated with higher levels of dynorphin peptides than alleles with 1 or 2 repeats (LL genotype). On the behavioral level, the HH group made more perseverative errors than the LL group. On the neural level, the HH group demonstrated less engagement of left orbitofrontal cortex (lOFC) and cortico-striatal circuitry, and lower effective connectivity of lOFC with anterior midcingulate cortex and anterior insula/ventrolateral prefrontal cortex during reversal learning and processing negative feedback. This points to a lower ability of the HH genotype to monitor or adapt to changes in reward contingencies. These findings provide first evidence that dynorphins may contribute to individual differences in reversal learning, and that considering the opioid system may shed new light on the neurochemical correlates of decision-making and behavioral regulation.

Keywords: functional MRI; genetics; opioid system; prodynorphin; reversal learning

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