Zokaei Nahid, Husain Masud
Oxford Centre for Human Brain Activity, University of Oxford, Oxford, UK.
Department of Experimental Psychology, University of Oxford, Oxford, UK.
Curr Top Behav Neurosci. 2019;41:325-344. doi: 10.1007/7854_2019_103.
Working memory impairments are frequently observed in patients with Alzheimer's disease (AD) and Parkinson's disease (PD). Recent research suggests that the mechanisms underlying these deficits might be dissociable using sensitive tasks, specifically those that rely on the reproduction of the exact quality of features held in memory.In patients with AD, working memory impairments are mainly due to an increase in misbinding errors. They arise when patients misremember which features (e.g., color, orientation, shape, and location) belong to different objects held in memory. Hence, they erroneously report features that belong to items in memory other than the one they are probed on. This misbinding of features that belong to different objects in memory can be considered a form of interference between stored items. Such binding errors are evident even in presymptomatic individuals with familial AD (due to gene mutations) who do not have AD yet. Overall, these findings are in line with the role of the medial temporal lobes, and specifically the hippocampus, in retention of feature bindings, regardless of retention duration, i.e., in both short- or long-term memory.Patients with PD, on the other hand, do not show increased misbinding. Their working memory deficits are associated with making more random errors or guesses. These random responses are not modulated by manipulations of their dopaminergic medication and hence may reflect involvement of non-dopaminergic neurotransmitters in this deficit. In addition, patients with PD demonstrate impairments in gating of information into relevant vs. irrelevant items in memory, a cognitive operation that is modulated by dopaminergic manipulation in line with a frontal executive effect of this neurotransmitter. Thus, although AD and PD are both associated with working memory impairments, these surface manifestations appear to be underpinned by very different mechanisms.
在阿尔茨海默病（AD）和帕金森病（PD）患者中经常观察到工作记忆障碍。最近的研究表明，使用敏感任务，特别是那些依赖于再现记忆中所保存特征的精确质量的任务，可能会揭示这些缺陷背后的机制。在AD患者中，工作记忆障碍主要是由于错误绑定错误的增加。当患者错误地记住哪些特征（例如颜色、方向、形状和位置）属于记忆中保存的不同对象时，就会出现这种情况。因此，他们错误地报告了属于记忆中除所探测对象之外的其他项目的特征。记忆中属于不同对象的特征的这种错误绑定可以被视为存储项目之间的一种干扰形式。即使在尚未患AD的有家族性AD（由于基因突变）的症状前个体中，这种绑定错误也很明显。总体而言，这些发现与内侧颞叶，特别是海马体在特征绑定保留中的作用一致，无论保留持续时间如何，即在短期或长期记忆中都是如此。另一方面，PD患者并没有表现出错误绑定的增加。他们的工作记忆缺陷与更多的随机错误或猜测有关。这些随机反应不受多巴胺能药物操作的调节，因此可能反映了非多巴胺能神经递质参与了这一缺陷。此外，PD患者在将信息区分为记忆中的相关项目与不相关项目方面存在障碍，这是一种认知操作，根据这种神经递质的额叶执行效应，它受多巴胺能操作的调节。因此，尽管AD和PD都与工作记忆障碍有关，但这些表面表现似乎由非常不同的机制所支撑。
