Behavioral analysis of NR2C knockout mouse reveals deficit in acquisition of conditioned fear and working memory

N-methyl-D-aspartate (NMDA) receptors play an important role in excitatory neurotransmission and mediate synaptic plasticity associated with learning and memory. NMDA receptors are composed of two NR1 and two NR2 subunits and the identity of the NR2 subunit confers unique electrophysiologic and pharmacologic properties to the receptor. The precise role of NR2C-containing receptors in vivo is poorly understood. We have performed a battery of behavioral tests on NR2C knockout/nβ-galactosidase knock-in mice and found no difference in spontaneous activity, basal anxiety, forced-swim immobility, novel object recognition, pain sensitivity and reference memory in comparison to wildtype counterparts. However, NR2C knockout mice were found to exhibit deficits in fear acquisition and working memory compared to wildtype mice. Deficit in fear acquisition correlated with lack of fear conditioning-induced plasticity at the thalamo-amygdala synapse. These findings suggest a unique role of NR2C-containing receptors in associative and executive learning representing a novel therapeutic target for deficits in cognition.     

Contextual cueing under working memory load: Selective interference of visuospatial load with expression of learning

In a series of experiments, we investigated the dependence of contextual cueing on working memory resources. A visual search task with 50 % repeated displays was run in order to elicit the implicit learning of contextual cues. The search task was combined with a concurrent visual working memory task either during an initial learning phase or a later test phase. The visual working memory load was either spatial or nonspatial. Articulatory suppression was used to prevent verbalization. We found that nonspatial working memory load had no effect, independent of presentation in the learning or test phase. In contrast, visuospatial load diminished search facilitation in the test phase, but not during learning. We concluded that visuospatial working memory resources are needed for the expression of previously learned spatial contexts, whereas the learning of contextual cues does not depend on visuospatial working memory.     

Independent operation of implicit working memory under cognitive load

Implicit working memory (WM) has been known to operate non-consciously and unintentionally. The current study investigated whether implicit WM is a discrete mechanism from explicit WM in terms of cognitive resource. To induce cognitive resource competition, we used a conjunction search task (Experiment 1) and imposed spatial WM load (Experiment 2a and 2b). Each trial was composed of a set of five consecutive search displays. The location of the first four displays appeared as per pre-determined patterns, but the fifth display could follow the same pattern or not. If implicit WM can extract the moving pattern of stimuli, response times for the fifth target would be faster when it followed the pattern compared to when it did not. Our results showed implicit WM can operate when participants are searching for the conjunction target and even while maintaining spatial WM information. These results suggest that implicit WM is independent from explicit spatial WM.     

条件性恐惧提取消退的性别差异

基于记忆再巩固理论的提取消退范式能够有效地削弱非适应性恐惧记忆。性别差异是个体差异性研究的关键变量, 但在提取消退范式的研究中仍然比较少见关于性别差异的探索。因此本研究以立体几何图形作为条件刺激, 腕部电击作为非条件刺激, 皮肤电反应为恐惧反应指标, 探究提取消退范式在恐惧消退效果上是否存在性别差异。结果表明, 在恐惧自发恢复测试中, 提取消退范式的所有被试都成功抑制了恐惧复发, 但恐惧重建测试中只有女性被试抑制了恐惧复发。这说明, 提取消退范式在抑制恐惧自发恢复方面效果显著, 在恐惧重建上女性的消退效果显著优于男性。     

Dissociation, cognitive failures, and working memory

The relationships between two personality measures (dissociation and cognitive failures) and different measures of interference from secondary tasks for working memory are investigated. Although the personality and cognitive measures were correlated with one another, canonical and bivariate correlations revealed no systematic relationships between the personality measures and the working memory measures. The upper bounds of the confidence intervals showed that, at most, only 10% of the variance was shared. We discuss the implications for theories of dissociation and cognitive functioning.     

工作记忆与知觉负载对工作记忆表征引导注意的调节

本研究采用4个眼动实验探讨不同知觉负载条件下的视觉搜索任务中工作记忆负载对基于工作记忆表征的注意引导效应的影响。实验1和实验3采用低知觉负载的视觉搜索任务,结果在视觉工作记忆负载为1和2时观察到了显著的注意引导效应,但当负载增加到4时注意引导效应消失了;实验2和实验4采用高知觉负载的视觉搜索任务,结果发现注意引导效应在工作记忆负载增加到2时就已经消失了。上述结果表明:工作记忆负载和知觉负载都能够通过调控认知资源的方式来影响工作记忆表征对注意的引导,当认知资源充足时,工作记忆能够同时保持多个记忆表征对视觉注意的引导。     

Right-sided human prefrontal brain activation during acquisition of conditioned fear

This H2(15)O positron emission tomography (PET) study reports on relative regional cerebral blood flow (rCBF) alterations during fear conditioning in humans. In the PET scanner, subjects viewed a TV screen with either visual white noise or snake videotapes displayed alone, then with electric shocks, followed by final presentations of white noise and snakes. Autonomic nervous system responses confirmed fear conditioning only to snakes. To reveal neural activation during acquisition, while equating sensory stimulation, scans during snakes with shocks and white noise alone were contrasted against white noise with shocks and snakes alone. During acquisition, rCBF increased in the right medial frontal gyrus, supporting a role for the prefrontal cortex in fear conditioning to unmasked evolutionary fear-relevant stimuli.     

Ensemble coding remains accurate under object and spatial visual working memory load

A number of studies have provided evidence that the visual system statistically summarizes large amounts of information that would exceed the limitations of attention and working memory (ensemble coding). However the necessity of working memory resources for ensemble coding has not yet been tested directly. In the current study, we used a dual task design to test the effect of object and spatial visual working memory load on size averaging accuracy. In Experiment 1, we tested participants’ accuracy in comparing the mean size of two sets under various levels of object visual working memory load. Although the accuracy of average size judgments depended on the difference in mean size between the two sets, we found no effect of working memory load. In Experiment 2, we tested the same average size judgment while participants were under spatial visual working memory load, again finding no effect of load on averaging accuracy. Overall our results reveal that ensemble coding can proceed unimpeded and highly accurately under both object and spatial visual working memory load, providing further evidence that ensemble coding reflects a basic perceptual process distinct from that of individual object processing.     

Time and cognitive load in working memory

According to the time-based resource-sharing model (P. Barrouillet, S. Bernardin, & V. Camos, 2004), the cognitive load a given task involves is a function of the proportion of time during which it captures attention, thus impeding other attention-demanding processes. Accordingly, the present study demonstrates that the disruptive effect on concurrent maintenance of memory retrievals and response selections increases with their duration. Moreover, the effect on recall performance of concurrent activities does not go beyond their duration insofar as the processes are attention demanding. Finally, these effects are not modality specific, as spatial processing was found to disrupt verbal maintenance. These results suggest a sequential and time-based function of working memory in which processing and storage rely on a single and general purpose attentional resource needed to run executive processes devoted to constructing, maintaining, and modifying ephemeral representations.     

Dissociation between appearance and location within visuo-spatial working memory

Previous research has demonstrated separation between systems supporting memory for appearance and memory for location. However, the interpretation of these results is complicated by a confound occurring because of the simultaneous presentation of objects in multiple-item arrays when assessing memory for appearance and the sequential presentation of items when assessing memory for location. This paper reports an experiment in which sequential or simultaneous modes of presentation were factorially manipulated with memory for visual appearance or memory for location. Spatial interference (tapping) or visual interference (dynamic visual noise) were presented during retention. Appearance versus location interacted with the type of interference task, but mode of presentation did not. These results are consistent with the view that different subsystems within visuo-spatial working memory support memory for appearance and memory for location.     

Dissociation between appearance and location within visuo-spatial working memory

Previous research has demonstrated separation between systems supporting memory for appearance and memory for location. However, the interpretation of these results is complicated by a confound occurring because of the simultaneous presentation of objects in multiple-item arrays when assessing memory for appearance and the sequential presentation of items when assessing memory for location. This paper reports an experiment in which sequential or simultaneous modes of presentation were factorially manipulated with memory for visual appearance or memory for location. Spatial interference (tapping) or visual interference (dynamic visual noise) were presented during retention. Appearance versus location interacted with the type of interference task, but mode of presentation did not. These results are consistent with the view that different subsystems within visuo-spatial working memory support memory for appearance and memory for location.     

Learning and memory in conditioned fear extinction: effects of D-cycloserine

This review addresses the effects of the cognitive enhancer D-cycloserine (DCS) on the memory processes that occur in conditioned fear extinction, which is the experimental model for exposure techniques to reduce clinical anxiety. All reported rat studies show an enhanced fear extinction effect when DCS is administered acutely before or shortly after extinction training. DCS also promotes the generalization of this fear extinction effect. In addition, DCS reduces some forms of relapse (reduced reinstatement, reduced spontaneous recovery), but not others (contextual renewal, rapid reacquisition). It is argued that this pattern of results is best explained by assuming that DCS promotes extinction learning to the background context, resulting in enhanced contextual inhibition. Four human studies have produced mixed results, but some methodological issues complicate the reported failures. It is concluded that DCS is a promising tool as an adjunct to extinction techniques in exposure treatment, but that more pre-clinical and clinical research is needed to fully characterize its behavioral consequences.     

Eye movements during recall of aversive memory decreases conditioned fear

Cognitive-behavioral therapy for anxiety disorders typically involves exposure to the conditioned stimulus (CS). Despite its status as an effective and primary treatment, many patients do not show clinical improvement or relapse. Contemporary learning theory suggests that treatment may be optimized by adding techniques that aim at revaluating the aversive consequence (US) of the feared stimulus. This study tested whether US devaluation via a dual task – imagining the US while making eye movements – decreases conditioned fear. Following fear acquisition one group recalled the US while making eye movements (EM) and one group merely recalled the US (RO). Next, during a test phase, all participants were re-presented the CSs. Dual tasking, relative to the control condition, decreased memory vividness and emotionality. Moreover, only in the dual task condition reductions were observed in self-reported fear, US expectancy, and CS unpleasantness, but not in skin conductance responses. Findings provide the first evidence that the dual task decreases conditioned fear and suggest it may be a valuable addition to exposure therapy.     

More conservative go/no-go response criterion under high working memory load

Previous work has shown that the efficiency of selective attention depends on the availability of cognitive control functions, including working memory. Here we examined the role of working memory in another task involving executive control, namely, a go/no-go task. Participants performed the Sustained Attention to Response Task, which requires withholding a prepotent response to an infrequent target, when at the same time placing a low or high load on an unrelated working memory task. Working memory load had the effect of reducing accuracy on the go trials, when at the same time increasing accuracy on the no-go trials. We interpret these findings to suggest that high working memory load led to a shift to a more conservative response criterion.     

The effect of hypocapnia on extinction of conditioned fear responses

Conditioning models have been very helpful in the understanding of the etiology and maintenance of anxiety. Such laboratory models, however, leave unexplained why in many cases of naturally occurring anxiety, as in the case of agoraphobia, the fear responses do not extinguish. Literature on experimental anxiety provocation suggests that a systemic alkalosis might play a role in the maintenance of phobic fear. It was hypothesized that a subject in a state of respiratory alkalosis would show delayed extinction to classical conditioned anxiety. In a differential classical conditioning paradigm, consisting of a habituation-, an acquisition-, and an extinction-phase, slides and electric shocks were used as conditioned stimuli (CS) and unconditioned stimuli (US) respectively. The skin conductance response was taken as (U)CR. Subjects were randomly assigned to two groups: hyperventilation or control. It was shown that the extinction was not delayed when subjects were hypocapnic during the extinction. These data support the view that a respiratory alkalosis per se is not a sufficient condition for the maintenance of neurotic fears. The data of the present study are discussed in the context of existing literature on a psychological interpretation of the maintenance of anxiety.     

Test-Anxiety,inferential reasoning and working memory load

Abstract

Subjects high and low in test-anxiety were presented with an inferential reasoning task requiring the verification of necessary and unnecessary inferences. The task was performed whilst holding either two or six digits in memory. On the verification task, the performance of high-test-anxious subjects was slower and less accurate than that of the low-test-anxious subjects. In addition, unnecessary inferences took longer to process than necessary inferences for the high-test-anxiety group only. The high-test-anxious subjects studied the memory loads for longer than the low-test-anxious group, but their recognition accuracy did not differ. Findings support Eysenck and Calvo's (Cognition and Emotion, 6, 409–434, 1992) processing efficiency theory. The high-test-anxious group's performance on the sentence verification task was impaired overall, and was particularly impaired when performing the unnecessary inference task. However, we also demonstrated that the high-test-anxious group's performance on a secondary memory task was unimpaired as a result of increased effort.     

认知重评阻断条件化恐惧记忆的习得与表达——对恐惧反应的长程抑制作用

情绪调节是人类特有的、并能有效控制个体情绪反应的行为方式,认知重评是其中最有效的调节策略之一。恐惧记忆是参与情绪障碍形成的重要病理机制,且已习得的恐惧反应难消退、易复发。为了考察认知重评能否起到长久抑制恐惧反应的效应,本研究利用条件化恐惧范式,第一天进行条件化恐惧习得训练,并在习得后间隔24 h及31天进行恐惧记忆的表达及自发恢复测试。实验1中,随机将被试分为两组,要求其在恐惧习得过程中进行认知重评或自然感受;在实验2,同样随机将被试分为两组,但要求其在恐惧记忆表达过程中进行认知重评或自然感受。结果发现,习得阶段进行认知重评显著降低了恐惧记忆的习得、表达及自发恢复过程中的SCR水平。同样,表达阶段进行认知重评也降低了此阶段的恐惧水平,且显著抑制了恐惧记忆的自发恢复。结果提示,在面对应激时,个体如果能够成功地利用想象进行认知重评,就有可能避免应激事件对个体的心理或精神造成伤害。     

Executive working memory load induces inattentional blindness

When attention is engaged in a task, unexpected events in the visual scene may go undetected, a phenomenon known as inattentional blindness (IB). At what stage of information processing must attention be engaged for IB to occur? Although manipulations that tax visuospatial attention can induce IB, the evidence is more equivocal for tasks that engage attention at late, central stages of information processing. Here, we tested whether IB can be specifically induced by central executive processes. An unexpected visual stimulus was presented during the retention interval of a working memory task that involved either simply maintaining verbal material or rearranging the material into alphabetical order. The unexpected stimulus was more likely to be missed during manipulation than during simple maintenance of the verbal information. Thus, the engagement of executive processes impairs the ability to detect unexpected, task-irrelevant stimuli, suggesting that IB can result from central, amodal stages of processing.