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携带与纹状体 D2 受体密度降低相关的遗传标志物(C957T 和 DRD2/ANKK1-TaqIA)的个体具有更好的认知目标维持能力。

Superior cognitive goal maintenance in carriers of genetic markers linked to reduced striatal D2 receptor density (C957T and DRD2/ANKK1-TaqIA).

机构信息

Aging Research Center, Karolinska Institutet and Stockholm University, Solna, Sweden.

Stress Research Institute, Stockholm University, Stockholm, Sweden.

出版信息

PLoS One. 2018 Aug 20;13(8):e0201837. doi: 10.1371/journal.pone.0201837. eCollection 2018.

Abstract

Maintaining goal representations is a critical component of cognitive control and is required for successful performance in many daily activities. This is particularly important when goal-relevant information needs to be maintained in working memory (WM), updated in response to changing task demands or internal goal states, and protected from interference by inhibiting counter-goal behaviors. Modulation of fronto-striatal dopamine is critical for updating and maintaining goals and representations. Here we test the hypothesis that a genetic predisposition (C957T T+ and DRD2/ANKK1-TaqIA A+) for reduced striatal D2 receptor availability would facilitate goal maintenance using the AX-continuous performance task (AX-CPT), on a sample of 196 adults (25-67 y). We demonstrate that carriers of two polymorphisms that have been linked to reduced striatal D2 receptor density show increased performance on context-dependent (BX) trials, and that the effect of these polymorphisms was only significant for long ISI trials where the demand for goal maintenance is high. The current results add further knowledge to the role of D2 receptor functioning in cognitive stability and flexibility, and could have implications for understanding cognitive deficits in patients characterized by altered dopamine functioning.

摘要

维持目标表示是认知控制的关键组成部分,对于成功完成许多日常活动至关重要。当需要在工作记忆 (WM) 中保持与目标相关的信息、根据不断变化的任务需求或内部目标状态进行更新,以及防止被抑制反目标行为干扰时,这一点尤为重要。前额叶纹状体多巴胺的调节对于更新和维持目标和表示至关重要。在这里,我们在一个由 196 名成年人(25-67 岁)组成的样本中,使用 AX-连续性能任务 (AX-CPT) 测试了以下假设:降低纹状体 D2 受体可用性的遗传倾向(C957T T+ 和 DRD2/ANKK1-TaqIA A+)会促进目标维持。我们证明,与降低纹状体 D2 受体密度相关的两种多态性的携带者在依赖于上下文的 (BX) 试验中表现出更高的性能,并且只有在长 ISI 试验中,这些多态性的影响才显著,因为在长 ISI 试验中,对目标维持的需求很高。目前的结果进一步证明了 D2 受体功能在认知稳定性和灵活性中的作用,并可能对理解多巴胺功能改变的患者的认知缺陷具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ec/6101371/027693a410df/pone.0201837.g001.jpg

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