Department of Experimental Psychology, University of Oxford, New Radcliffe House, Walton Street, Oxford, OX2 6AG, UK.
Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Cereb Cortex. 2017 Dec 1;27(12):5727-5738. doi: 10.1093/cercor/bhx242.
Deficits in working memory (WM) in Parkinson's disease (PD) are often considered to be secondary to dopaminergic depletion. However, the neurocognitive mechanisms by which dopamine causes these deficits remain highly contested, and PD is now also known to be associated with nondopaminergic pathology. Here, we examined how PD and dopaminergic medication modulate three components of WM: maintenance over time, updating contents with new information and making memories distracter-resistant. Compared with controls, patients were disproportionately impaired when retaining information for longer durations. By applying a probabilistic model, we were able to reveal that the source of this error was selectively due to precision of memory representations degrading over time. By contrast, replenishing dopamine levels in PD improved executive control over both the ability to ignore and update, but did not affect maintenance of information across time. This was due to a decrease in guess responses, consistent with the view that dopamine serves to prevent WM representations being corrupted by irrelevant information, but has no impact on information decay. Cumulatively, these results reveal a dissociation in the neural mechanisms underlying poor WM: whereas dopamine reduces interference, nondopaminergic systems in PD appear to modulate processes that prevent information decaying more quickly over time.
帕金森病（PD）患者的工作记忆（WM）缺陷通常被认为是多巴胺能耗竭的结果。然而，多巴胺引起这些缺陷的神经认知机制仍存在很大争议，现在也知道 PD 与非多巴胺能病理学有关。在这里，我们研究了 PD 和多巴胺能药物如何调节 WM 的三个组成部分：随时间的维持、用新信息更新内容以及使记忆不受干扰。与对照组相比，患者在长时间保留信息时受到不成比例的损害。通过应用概率模型，我们能够揭示出这种错误的原因是记忆表示的精度随时间退化而选择性地导致的。相比之下，在 PD 中补充多巴胺水平改善了对忽略和更新的执行控制，但不会影响随时间推移信息的维持。这是由于猜测反应减少所致，这与多巴胺有助于防止 WM 表示受到无关信息干扰的观点一致，但对信息衰减没有影响。总之，这些结果揭示了不良 WM 背后的神经机制的分离：多巴胺减少干扰，而 PD 中的非多巴胺能系统似乎调节了防止信息随时间更快衰减的过程。
