Fallon Sean James, van der Schaaf Marieke E, Ter Huurne Niels, Cools Roshan
Radboud University Donders Institute of Brain, Cognition, and Behavior.
University of Oxford.
J Cogn Neurosci. 2017 Apr;29(4):652-663. doi: 10.1162/jocn_a_01065. Epub 2016 Oct 25.
A balance has to be struck between supporting distractor-resistant representations in working memory and allowing those representations to be updated. Catecholamine, particularly dopamine, transmission has been proposed to modulate the balance between the stability and flexibility of working memory representations. However, it is unclear whether drugs that increase catecholamine transmission, such as methylphenidate, optimize this balance in a task-dependent manner or bias the system toward stability at the expense of flexibility (or vice versa). Here we demonstrate, using pharmacological fMRI, that methylphenidate improves the ability to resist distraction (cognitive stability) but impairs the ability to flexibly update items currently held in working memory (cognitive flexibility). These behavioral effects were accompanied by task-general effects in the striatum and opposite and task-specific effects on neural signal in the pFC. This suggests that methylphenidate exerts its cognitive enhancing and impairing effects through acting on the pFC, an effect likely associated with methylphenidate's action on the striatum. These findings highlight that methylphenidate acts as a double-edged sword, improving one cognitive function at the expense of another, while also elucidating the neurocognitive mechanisms underlying these paradoxical effects.
必须在支持工作记忆中抗干扰表征与允许这些表征更新之间取得平衡。有人提出儿茶酚胺，尤其是多巴胺传递，可调节工作记忆表征的稳定性和灵活性之间的平衡。然而，尚不清楚诸如哌甲酯等增加儿茶酚胺传递的药物是以任务依赖的方式优化这种平衡，还是以使系统偏向稳定性为代价而牺牲灵活性（反之亦然）。在这里，我们使用药理功能磁共振成像证明，哌甲酯提高了抵抗干扰的能力（认知稳定性），但损害了灵活更新当前工作记忆中项目的能力（认知灵活性）。这些行为效应伴随着纹状体中的任务通用效应以及前额叶皮质中神经信号的相反且任务特异性的效应。这表明哌甲酯通过作用于前额叶皮质发挥其认知增强和损害作用，这种效应可能与哌甲酯对纹状体的作用有关。这些发现突出表明哌甲酯是一把双刃剑，以牺牲另一种认知功能为代价来改善一种认知功能，同时也阐明了这些矛盾效应背后的神经认知机制。
