Mechanisms underlying corruption of working memory in Parkinson's disease

Working memory (WM) impairments are reported to occur in patients with Parkinson's disease (PD). However, the mechanisms are unclear. Here, we investigate several putative factors that might drive poor performance, by examining the precision of recall, the order in which items are recalled and whether memories are corrupted by random guessing (attentional lapses). We used two separate tasks that examined the quality of WM recall under different loads and retention periods, as well as a traditional digit span test. Firstly, on a simple measure of WM recall, where patients were asked to reproduce the orientation of a centrally presented arrow, overall recall was not significantly impaired. However, there was some evidence for increased guessing (attentional lapses). On a new analogue version of the Corsi-span task, where participants had to reproduce on a touchscreen the exact spatial pattern of presented stimuli in the order and locations in which they appeared, there was a reduction in the precision of spatial WM at higher loads. This deficit was due to misremembering item order. At the highest load, there was reduced recall precision, whereas increased guessing was only observed at intermediate set sizes. Finally, PD patients had impaired backward, but not forward, digit spans. Overall, these results reveal the task- and load-dependent nature of WM deficits in PD. On simple low-load tasks, attentional lapses predominate, whereas at higher loads, in the spatial domain, the corruption of mnemonic information—both order item and precision—emerge as the main driver of impairment.     

Molecular activity underlying working memory

The prefrontal cortex is necessary for directing thought and planning action. Working memory, the active, transient maintenance of information in mind for subsequent monitoring and manipulation, lies at the core of many simple, as well as high-level, cognitive functions. Working memory has been shown to be compromised in a number of neurological and psychiatric conditions and may contribute to the behavioral and cognitive deficits associated with these disorders. It has been theorized that working memory depends upon reverberating circuits within the prefrontal cortex and other cortical areas. However, recent work indicates that intracellular signals and protein dephosphorylation are critical for working memory. The present article will review recent research into the involvement of the modulatory neurotransmitters and their receptors in working memory. The intracellular signaling pathways activated by these receptors and evidence that indicates a role for G(q)-initiated PI-PLC and calcium-dependent protein phosphatase calcineurin activity in working memory will be discussed. Additionally, the negative influence of calcium- and cAMP-dependent protein kinase (i.e., calcium/calmodulin-dependent protein kinase II (CaMKII), calcium/diacylglycerol-activated protein kinase C (PKC), and cAMP-dependent protein kinase A (PKA)) activities on working memory will be reviewed. The implications of these experimental findings on the observed inverted-U relationship between D(1) receptor stimulation and working memory, as well as age-associated working memory dysfunction, will be presented. Finally, we will discuss considerations for the development of clinical treatments for working memory disorders.     

Visual working memory for trained and novel polygons

This study investigates whether training changes the capacity of visual working memory (VWM). We compared change detection performance for novel and trained polygons. During training, subjects developed familiarity with 8 random polygons. Specifically, 4 polygons from a set of 8 were presented on each trial. After a brief retention interval, one of the polygons changed and subjects judged which one had changed (Exps. 1–2) or whether there was a change (Exp. 3). After 320 training trials, subjects could recognize the trained polygons with high accuracy. In the testing phase, subjects carried out the same task again, only this time each trial might contain all familiar polygons, all novel polygons, or a mixture of familiar and novel polygons. We found that change detection performance improved during training, but the improvement was not limited to trained polygons. We suggest that familiarity of non-nameable shapes plays a limited role in modulating the capacity of VWM.     

Recognition and position information in working memory for visual textures

In three experiments, we examined connections between item-recognition memory and memory for item-position information. With sequences of compound gratings as study and probe items, subjects made either item-position judgments (Experiments 1 and 2), by identifying the serial position of the study item that matched the probe, or recognition judgments (Experiment 3), by judging whether the probe had or had not been presented in the study series. Integrating a summed-similarity account of recognition into a signal detection framework shows that the variance of summed similarities on lure trials (probe not present in the study series) exceeds the variance on target trials (probe present in the study series). This prediction is borne out by the empirical zROC functions, all of which had slopes that were greater than 1. Additionally, about 25% of correct recognitions were accompanied by incorrect item position identification. Misidentifications of item position arose from two sources--structural similarity and positional similarity-which combined in an approximately additive fashion.     

Visual working memory for global,object, and part-based information

We investigated visual working memory for novel objects and parts of novel objects. After a delay period, participants showed strikingly more accurate performance recognizing a single whole object than the parts of that object. This bias to remember whole objects, rather than parts, persisted even when the division between parts was clearly defined and the parts were disconnected from each other so that, in order to remember the single whole object, the participants needed to mentally combine the parts. In addition, the bias was confirmed when the parts were divided by color. These experiments indicated that holistic perceptual-grouping biases are automatically used to organize storage in visual working memory. In addition, our results suggested that the bias was impervious to top-down consciously directed control, because when task demands were manipulated through instruction and catch trials, the participants still recognized whole objects more quickly and more accurately than their parts. This bias persisted even when the whole objects were novel and the parts were familiar. We propose that visual working memory representations depend primarily on the global configural properties of whole objects, rather than part-based representations, even when the parts themselves can be clearly perceived as individual objects. This global configural bias beneficially reduces memory load on a capacity-limited system operating in a complex visual environment, because fewer distinct items must be remembered.     

Updating information in verbal working memory and executive functioning

50 older adults (M age=77.9 yr., SD=7.3; 35 women and 15 men) were tested using the updating working-memory task. They were also given the neuropsychological Wisconsin Card Sorting Test, assumed to evaluate executive functioning and the frontal cortex. A factor analysis with age, education, and verbal ability partialled out was computed on the updating task outcomes and resulted in a two-factor solution, indicating that this task requires two independent processes, interpreted as reflecting a storage component and an updating component. Partial correlations with age, education, and verbal ability partialled out indicated that Wisconsin Card Sorting Test measures were significantly associated with the factor supposed to reflect the updating process. Such results appeared consistent with the model of working memory with a central executive system involved in the updating process and related to the executive-frontal functioning, and a phonological loop system involved in the storage of verbal information and not linked to executive-frontal functions.     

Guidance of attention by information held in working memory

Information held in working memory (WM) can guide attention during visual search. The authors of recent studies have interpreted the effect of holding verbal labels in WM as guidance of visual attention by semantic information. In a series of experiments, we tested how attention is influenced by visual features versus category-level information about complex objects held in WM. Participants either memorized an object’s image or its category. While holding this information in memory, they searched for a target in a four-object search display. On exact-match trials, the memorized item reappeared as a distractor in the search display. On category-match trials, another exemplar of the memorized item appeared as a distractor. On neutral trials, none of the distractors were related to the memorized object. We found attentional guidance in visual search on both exact-match and category-match trials in Experiment 1, in which the exemplars were visually similar. When we controlled for visual similarity among the exemplars by using four possible exemplars (Exp. 2) or by using two exemplars rated as being visually dissimilar (Exp. 3), we found attentional guidance only on exact-match trials when participants memorized the object’s image. The same pattern of results held when the target was invariant (Exps. 2–3) and when the target was defined semantically and varied in visual features (Exp. 4). The findings of these experiments suggest that attentional guidance by WM requires active visual information.     

Sensitive maintenance: a cognitive process underlying individual differences in memory for threatening information

Dispositional styles of coping with threat influence memory for threatening information. In particular, sensitizers excel over repressors in their memory for threatening information after long retention intervals, but not after short ones. We therefore suggested that sensitizers, but not repressors, employ active maintenance processes during the retention interval to selectively retain threatening material. Sensitive maintenance was studied in 2 experiments in which participants were briefly exposed to threatening and nonthreatening pictures (Experiment 1, N = 128) or words (Experiment 2, N = 145). Following, we administered unannounced recognition tests before and after an intervening task that generated either high or low cognitive load, assuming that high cognitive load would impede sensitizers' memory maintenance of threatening material. Supporting our hypotheses, the same pattern of results was obtained in both experiments: Under low cognitive load, sensitizers forgot less threat material than repressors did; no such differences were observed under high cognitive load.     

Maintenance of item and order information in verbal working memory

Although verbal recall of item and order information is well-researched in short-term memory paradigms, there is relatively little research concerning item and order recall from working memory. The following study examined whether manipulating the opportunity for attentional refreshing and articulatory rehearsal in a complex span task differently affected the recall of item- and order-specific information of the memoranda. Five experiments varied the opportunity for articulatory rehearsal and attentional refreshing in a complex span task, but the type of recall was manipulated between experiments (item and order, order only, and item only recall). The results showed that impairing attentional refreshing and articulatory rehearsal similarly affected recall regardless of whether the scoring procedure (Experiments 1 and 4) or recall requirements (Experiments 2, 3, and 5) reflected item- or order-specific recall. This implies that both mechanisms sustain the maintenance of item and order information, and suggests that the common cumulative functioning of these two mechanisms to maintain items could be at the root of order maintenance.     

Not all information in visual working memory is forgotten equally

To improve maintenance of task-relevant information in visual working memory (VWM), previously encoded, but no longer relevant, information can be suppressed or forgotten. However, it is unclear whether a cue directing attention to a subset of stimuli leads to complete forgetting for non-cued stimuli. The current study utilized a novel method of testing to-be forgotten information to determine if the effectiveness of forgetting differs depending on the type of encoded stimuli. Participants performed a directed forgetting change detection task, and importantly, the changed stimulus could be a novel stimulus or a to-be-forgotten stimulus. Stimulus type (colors, objects, or shapes) was manipulated across two experiments. Results suggest that a cue benefits memory for to-be-remembered information, but performance is not equivalent to never encoding to-be-forgotten information. Furthermore, the type of encoded information impacts the extent of forgetting.     

Consolidation of statistical information of multiple objects in working memory

The present study investigated working memory consolidation in focused and distributed attention tasks by examining the time course of the consolidation process (Experiment 1) and its dependence on capacity-limited central resources (Experiment 2) in both tasks. In a match-to-sample design using masks at various intervals to vary consolidation rates, the participants performed either an identification task (focused attention) or a mean estimation task (distributed attention) with (Experiment 1) or without (Experiment 2) prior knowledge of what task they were to perform. We found that consolidation in the distributed attention task was more efficient and was about twice as fast as in the focused attention task. In addition, both tasks suffered interference when they had to be performed together, indicating that both types of attention rely on a common set of control processes. These findings can be attributed to differences in the resolution of object representations and in the scope of attention associated with focused and distributed attention.     

The neural correlates of updating information in verbal working memory

The aim of the present study was to re-examine cerebral areas subserving the updating function of the central executive with a running span task requiring subjects to watch strings of consonants of unknown length and then to recall serially a specific number of recent items. In order to dissociate more precisely the updating process from the storage function, a four-item instead of a six-item memory load was used, contrary to our previous study (Salmon et al., 1996). In addition, a serial recall procedure was preferred to a recognition procedure in order to suppress the use of visuospatial strategies. The most significant increase of rCBF occurred in the left frontopolar cortex (Brodmann's area 10), spreading to the left middle frontal (Brodmann's area 46). Results suggest that frontopolar activation underlies an updating process in working memory.     

Early adversity in rural India impacts the brain networks underlying visual working memory

There is a growing need to understand the global impact of poverty on early brain and behavioural development, particularly with regard to key cognitive processes that emerge in early development. Although the impact of adversity on brain development can trap children in an intergenerational cycle of poverty, the massive potential for brain plasticity is also a source of hope: reliable, accessible, culturally agnostic methods to assess early brain development in low resource settings might be used to measure the impact of early adversity, identify infants for timely intervention and guide the development and monitor the effectiveness of early interventions. Visual working memory (VWM) is an early marker of cognitive capacity that has been assessed reliably in early infancy and is predictive of later academic achievement in Western countries. Here, we localized the functional brain networks that underlie VWM in early development in rural India using a portable neuroimaging system, and we assessed the impact of adversity on these brain networks. We recorded functional brain activity as young children aged 4–48 months performed a VWM task. Brain imaging results revealed localized activation in the frontal cortex, replicating findings from a Midwestern US sample. Critically, children from families with low maternal education and income showed weaker brain activity and poorer distractor suppression in canonical working memory areas in the left frontal cortex. Implications of this work are far‐reaching: it is now cost‐effective to localize functional brain networks in early development in low‐resource settings, paving the way for novel intervention and assessment methods.     

Training the removal of negative information from working memory: A preliminary investigation of a working memory bias modification task

Rumination in depressed adults is associated with a bias toward retaining negative information in working memory. We developed a task designed to modify this cognitive bias by having subjects repeatedly practice removing negative words from working memory, thereby enabling them to retain positive and neutral words. To assess the efficacy of this task, we recruited 60 adults who reported elevated repetitive negative thought (RNT) and randomly assigned them to receive a single administration of either the working memory bias modification (WMBM) task or a control task. Subjects in the WMBM condition exhibited greater reduction in proactive interference for negative information than did those in the control condition. These results suggest that the WMBM task reduces biased retention of negative information in working memory and, thus, may be useful in investigating the possible causal role of this cognitive bias in RNT or depression.     

抑郁症患者工作记忆内情绪刺激加工的特点及其机制

抑郁症患者在工作记忆内情绪刺激加工的特点为倾向于加工与负性心境一致的材料, 被认为是抑郁症认知易感性的核心特征。目前研究者们围绕抑郁症工作记忆中央执行系统三个子功能的情绪刺激加工特点及其作用机制进行了大量研究, 发现在更新功能上, 患者难以移除负性情绪信息, 且在正性信息的加工上存在缺损; 在抑制功能上, 患者难以抑制无关负性情绪信息进入工作记忆; 在转换功能上, 患者情绪材料转换困难的研究证据尚不充分。神经生理与脑成像的研究初步表明, 工作记忆中的情绪刺激加工与抑郁症患者背外侧前额叶和前扣带回的功能激活水平异常有关。未来研究需评估工作记忆三个子功能对抑郁症状的差异性贡献及在情绪刺激加工上的统一性, 并探究其随疾病发生发展变化的轨迹, 谨慎选取并评估不同情绪刺激材料指标的诱发效应及其对工作记忆功能的独特影响。在此基础上, 深入探究工作记忆内情绪刺激加工的神经机制, 为工作记忆偏向矫正干预的临床应用及其预期效果提供理论依据和方向。     

Visual working memory retains movement information within an allocentric reference frame

What frame of reference do we use to remember observed movements? One possibility is that visual working memory (VWM) retains movement information using a retinotopic frame of reference: A coordinate system with respect to the retina that retains view-dependent information. Alternatively, VWM might retain movement information using an allocentric frame of reference: A coordinate system with respect to the scene that retains view-invariant information. To address this question, I examined whether VWM retains view-dependent or view-invariant movement information. Results show that (1) observers have considerable difficulty remembering from which viewpoints they observed movements after a few seconds' delay, and (2) the same number of movements can be retained in VWM whether the movements are encoded and tested from the same viewpoint or from different viewpoints. Thus, movement representations contain little to no view-dependent information, which suggests that VWM uses an allocentric reference frame to retain movement information.     

Misleading postevent information and working memory capacity: an individual differences approach to eyewitness memory

The present study examines how individual differences in working memory capacity relate to the effect of misleading postevent information on memory for the original event. Participants were shown a film of a crime event and were then asked to unscramble a narrative that included misinformation regarding some of the film's details. Additionally, the working memory capacity of the participants was measured using the operation‐word span task. Finally, in a free recall test, participants recalled fewer correct details in the misinformation condition compared to the control condition. This effect was negatively correlated with working memory capacity. Copyright © 2002 John Wiley & Sons, Ltd.     

错误记忆产生的认知与神经机制：信息加工视角

采用信息加工视角, 在划分不同信息来源的基础上分析编码、存储(巩固)、再激活/再巩固和提取的一系列加工过程如何导致错误记忆形成, 由此总结出错误记忆产生的三个可能原因：(1)因缺乏针对目标事物特异性细节的记忆表征而侧重于编码和提取目标和非目标事物共享的抽象记忆表征, 使被试更倾向于依赖抽象表征对缺失的目标细节进行重构, 引发错误记忆; (2)目标事物启动了对应图式, 导致与图式相关的非目标事物记忆表征得到增强, 引发错误记忆; (3)误导信息干扰了再度激活状态下目标事物的记忆表征, 妨碍其进行准确的记忆再巩固, 从而引发错误记忆。未来研究可进一步探讨目标事物特异性细节的表征区域、不同类型的图式表征促进非目标事物记忆表征的具体机制以及提取阶段的图式复现对错误记忆形成的影响等问题。