Shiner T, Symmonds M, Guitart-Masip M, Fleming S M, Friston K J, Dolan R J
Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London WC1N 3BG, UK.
Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London WC1N 3BG, UK Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Cereb Cortex. 2015 Oct;25(10):3629-39. doi: 10.1093/cercor/bhu210. Epub 2014 Sep 21.
Dopamine is implicated in multiple functions, including motor execution, action learning for hedonically salient outcomes, maintenance, and switching of behavioral response set. Here, we used a novel within-subject psychopharmacological and combined functional neuroimaging paradigm, investigating the interaction between hedonic salience, dopamine, and response set shifting, distinct from effects on action learning or motor execution. We asked whether behavioral performance in response set shifting depends on the hedonic salience of reversal cues, by presenting these as null (neutral) or salient (monetary loss) outcomes. We observed marked effects of reversal cue salience on set-switching, with more efficient reversals following salient loss outcomes. L-Dopa degraded this discrimination, leading to inappropriate perseveration. Generic activation in thalamus, insula, and striatum preceded response set switches, with an opposite pattern in ventromedial prefrontal cortex (vmPFC). However, the behavioral effect of hedonic salience was reflected in differential vmPFC deactivation following salient relative to null reversal cues. l-Dopa reversed this pattern in vmPFC, suggesting that its behavioral effects are due to disruption of the stability and switching of firing patterns in prefrontal cortex. Our findings provide a potential neurobiological explanation for paradoxical phenomena, including maintenance of behavioral set despite negative outcomes, seen in impulse control disorders in Parkinson's disease.
多巴胺参与多种功能，包括运动执行、对享乐主义显著结果的动作学习、行为反应集的维持和转换。在此，我们采用了一种新颖的受试者内心理药理学和联合功能神经成像范式，研究享乐主义显著性、多巴胺和反应集转换之间的相互作用，这与对动作学习或运动执行的影响不同。我们通过将反转线索呈现为无（中性）或显著（金钱损失）结果，来探究反应集转换中的行为表现是否取决于反转线索的享乐主义显著性。我们观察到反转线索显著性对集转换有显著影响，在显著损失结果后反转更有效。左旋多巴削弱了这种辨别能力，导致不适当的持续行为。在反应集转换之前，丘脑、岛叶和纹状体出现一般激活，而腹内侧前额叶皮层（vmPFC）则呈现相反模式。然而，享乐主义显著性的行为效应反映在相对于无反转线索，显著反转线索后vmPFC的失活差异上。左旋多巴逆转了vmPFC中的这种模式，表明其行为效应是由于前额叶皮层放电模式的稳定性和转换受到破坏。我们的研究结果为帕金森病冲动控制障碍中出现的矛盾现象，包括尽管有负面结果仍维持行为集，提供了一种潜在的神经生物学解释。
