情节记忆中的前摄干扰：神经心理药物学及计算认知建模研究

记忆障碍患者的前摄干扰敏感性显著上升, 但其认知机制仍不清楚。结合神经心理药物学实验和计算认知建模方法对这一问题进行了研究。实验为被试内、双盲设计, 由健康成年人进行两次词对任务的学习, 间隔一周, 两次测试中或注射0.03 mg/kg体重咪唑安定或注射相同浓度的生理盐水。学习过程中及学习结束后进行测试, 要求被试根据线索词回忆靶词。实验结果发现, 注射咪唑安定可引起情节记忆的短时下降, 两种注射条件下均呈现明显的前摄干扰; 与生理盐水条件相比, 注射咪唑安定时引起的前摄干扰显著较高。基于SAC (Source of Action Confusion)的计算认知建模结果较好地拟合了实验数据。这一结果提示, 编码困难可能是记忆障碍患者前摄干扰敏感性较高的主要原因。

Proactive Interference in Episodic Memory: Neuropsychopharmacology and Computational Cognitive Modeling Study

Increased sensitivity to proactive interference (PI) was widely observed in patients with memory impairment. There were two competing theories proposed to account for the susceptible PI effect in amnesia patients, with one holds that PI occurs at encoding stage, and the other believes that PI occurs at retrieval stage, however, its underlying mechanism was still unclear. Moreover, the results from patient study may be confounded by the differences of age, gender, education level and intelligence between patients and controls. The present study focused on this issue by in combination using neuropsychopharmacological experiment and computational cognitive modeling technique. Based on the recent findings from amnesic mild cognitive impairments (aMCI) that encoding impairment and susceptible PI effect coexisted in aMCI, and susceptible PI effect still remained in the absence of response competition, we hypothesized that the susceptible PI effect in amnesic patients might be primarily due to encoding deficits. 20 healthy adults (11 females) voluntarily participated in a double-blind, between-subject, placebo- controlled experiment, with a 2 (drug: midazolam, saline) × 3 (list: list1, list2, list3) × 3 (word pairs: control, interference, practice) factorial design. Subjects were required to participate the experiment twice, one week apart, under midazolam (0.03 mg/kg) or saline. In each day, subjects went through 3 lists of word-pair associative learning tasks and a final cued-recall test. For each list, subjects were asked to remember 45 word pairs firstly, and then each word pair was tested twice. Three kinds of word pairs were designed, with control pairs studied on only one list, practice pairs practiced on all three lists, and interference pairs involved recombining cue and response terms from one list to the next. An ANOVA statistical analysis was run on behavioral data and SAC (Source of Action Confusion) models were constructed accordingly. It was found that, episodic memory was significantly reduced after midazolam injection, as contrast to saline injection. In list2, the list directly followed the injection, the PI effect was detected both under midazolam and saline, but the PI magnitude under midazolam was significantly higher than that under saline. The similar pattern was also observed in list3, although not to be significant. The output of the SAC model was fitted well with the experimental data. In conclusion, by using drug studies, we replicated and further demonstrated the susceptible PI effect in amnesic subjects. Moreover, with SAC, the present findings suggested that the increased sensitivity of PI under midazolam, as compared with saline, may be due to the encoding impairment under midazolam. The present finding implies that the sensitive PI effect in amnesic patients, such as aMCI and Alzheimer's Disease (AD), may be due to encoding deficit, and thus may contribute to the diagnosis and cognitive training of these patients.