Changes in brain activation during working memory and facial recognition tasks in patients with bipolar disorder with Lamotrigine monotherapy

Verbal working memory and emotional self-regulation are impaired in Bipolar Disorder (BD). Our aim was to investigate the effect of Lamotrigine (LTG), which is effective in the clinical management of BD, on the neural circuits subserving working memory and emotional processing. Functional Magnetic Resonance Imaging data from 12 stable BD patients was used to detect LTG-induced changes as the differences in brain activity between drug-free and post-LTG monotherapy conditions during a verbal working memory (N-back sequential letter task) and an angry facial affect recognition task. For both tasks, LGT monotherapy compared to baseline was associated with increased activation mostly within the prefrontal cortex and cingulate gyrus, in regions normally engaged in verbal working memory and emotional processing. Therefore, LTG monotherapy in BD patients may enhance cortical function within neural circuits involved in memory and emotional self-regulation. © 2007 Elsevier B.V. and ECNP.

The role of prior exposure on the capture of attention by items in working memory

The Biased Competition Model (BCM) suggests both top-down and bottom-up biases operate on selective attention (e.g., Desimone & Duncan, 1995). It has been suggested that top-down control signals may arise from working memory. In support, Downing (2000) found faster responses to probes presented in the location of stimuli held vs. not held in working memory. Soto, Heinke, Humphreys, and Blanco (2005) showed the involuntary nature of this effect and that shared features between stimuli were sufficient to attract attention. Here we show that stimuli held in working memory had an influence on the deployment of attentional resources even when: (1) It was detrimental to the task, (2) there was equal prior exposure, and (3) there was no bottom-up priming. These results provide further support for involuntary top-down guidance of attention from working memory and the basic tenets of the BCM, but further discredit the notion that bottom-up priming is necessary for the effect to occur.

A working memory bias for alcohol-related stimuli depends on drinking score

We tested 44 participants with respect to their working memory (WM) performance on alcohol-related versus neutral visual stimuli. Previously an alcohol attentional bias (AAB) had been reported using these stimuli, where the attention of frequent drinkers was automatically drawn toward alcohol-related items (e.g., beer bottle). The present study set out to provide evidence for an alcohol memory bias (AMB) that would persist over longer time-scales than the AAB. The WM task we used required memorizing 4 stimuli in their correct locations and a visual interference task was administered during a 4-sec delay interval. A subsequent probe required participants to indicate whether a stimulus was shown in the correct or incorrect location. For each participant we calculated a drinking score based on 3 items derived from the Alcohol Use Questionnaire, and we observed that higher scorers better remembered alcohol-related images compared with lower scorers, particularly when these were presented in their correct locations upon recall. This provides first evidence for an AMB. It is important to highlight that this effect persisted over a 4-sec delay period including a visual interference task that erased iconic memories and diverted attention away from the encoded items, thus the AMB cannot be reduced to the previously reported AAB. Our finding calls for further investigation of alcohol-related cognitive biases in WM, and we propose a preliminary model that may guide future research. © 2012 American Psychological Association.

How checking breeds doubt:reduced performance in a simple working memory task

A paradox of memory research is that repeated checking results in a decrease in memory certainty, memory vividness and confidence [van den Hout, M. A., & Kindt, M. (2003a). Phenomenological validity of an OCD-memory model and the remember/know distinction. Behaviour Research and Therapy, 41, 369–378; van den Hout, M. A., & Kindt, M. (2003b). Repeated checking causes memory distrust. Behaviour Research and Therapy, 41, 301–316]. Although these findings have been mainly attributed to changes in episodic long-term memory, it has been suggested [Shimamura, A. P. (2000). Toward a cognitive neuroscience of metacognition. Consciousness and Cognition, 9, 313–323] that representations in working memory could already suffer from detrimental checking. In two experiments we set out to test this hypothesis by employing a delayed-match-to-sample working memory task. Letters had to be remembered in their correct locations, a task that was designed to engage the episodic short-term buffer of working memory [Baddeley, A. D. (2000). The episodic buffer: a new component in working memory? Trends in Cognitive Sciences, 4, 417–423]. Of most importance, we introduced an intermediate distractor question that was prone to induce frustrating and unnecessary checking on trials where no correct answer was possible. Reaction times and confidence ratings on the actual memory test of these trials confirmed the success of this manipulation. Most importantly, high checkers [cf. VOCI; Thordarson, D. S., Radomsky, A. S., Rachman, S., Shafran, R, Sawchuk, C. N., & Hakstian, A. R. (2004). The Vancouver obsessional compulsive inventory (VOCI). Behaviour Research and Therapy, 42(11), 1289–1314] were less accurate than low checkers when frustrating checking was induced, especially if the experimental context actually emphasized the irrelevance of the misleading question. The clinical relevance of this result was substantiated by means of an extreme groups comparison across the two studies. The findings are discussed in the context of detrimental checking and lack of distractor inhibition as a way of weakening fragile bindings within the episodic short-term buffer of Baddeley's (2000) model. Clinical implications, limitations and future research are considered.

Dynamic causal modeling of load-dependent modulation of effective connectivity within the verbal working memory network

Neuroimaging studies have consistently shown that working memory (WM) tasks engage a distributed neural network that primarily includes the dorsolateral prefrontal cortex, the parietal cortex, and the anterior cingulate cortex. The current challenge is to provide a mechanistic account of the changes observed in regional activity. To achieve this, we characterized neuroplastic responses in effective connectivity between these regions at increasing WM loads using dynamic causal modeling of functional magnetic resonance imaging data obtained from healthy individuals during a verbal n-back task. Our data demonstrate that increasing memory load was associated with (a) right-hemisphere dominance, (b) increasing forward (i.e., posterior to anterior) effective connectivity within the WM network, and (c) reduction in individual variability in WM network architecture resulting in the right-hemisphere forward model reaching an exceedance probability of 99% in the most demanding condition. Our results provide direct empirical support that task difficulty, in our case WM load, is a significant moderator of short-term plasticity, complementing existing theories of task-related reduction in variability in neural networks. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.

Frontopolar cortical inefficiency may underpin reward and working memory dysfunction in bipolar disorder

Objectives. Emotional dysregulation in bipolar disorder is thought to arise from dysfunction within prefrontal cortical regions involved in cognitive control coupled with increased or aberrant activation within regions engaged in emotional processing. The aim of this study was to determine the common and distinct patterns of functional brain abnormalities during reward and working memory processing in patients with bipolar disorder. Methods. Participants were 36 euthymic bipolar disorder patients and 37 healthy comparison subjects matched for age, sex and IQ. Functional magnetic resonance imaging (fMRI) was conducted during the Iowa Gambling Task (IGT) and the n-back working memory task. Results. During both tasks, patients with bipolar disorder demonstrated a pattern of inefficient engagement within the ventral frontopolar prefrontal cortex with evidence of segregation along the medial-lateral dimension for reward and working memory processing, respectively. Moreover, patients also showed greater activation in the anterior cingulate cortex during the Iowa Gambling Task and in the insula during the n-back task. Conclusions. Our data implicate ventral frontopolar dysfunction as a core abnormality underpinning bipolar disorder and confirm that overactivation in regions involved in emotional arousal is present even in tasks that do not typically engage emotional systems. © 2012 Informa Healthcare.

What checkers actually check:an eye tracking study of inhibitory control and working memory

Background - Not only is compulsive checking the most common symptom in Obsessive Compulsive Disorder (OCD) with an estimated prevalence of 50–80% in patients, but approximately ~15% of the general population reveal subclinical checking tendencies that impact negatively on their performance in daily activities. Therefore, it is critical to understand how checking affects attention and memory in clinical as well as subclinical checkers. Eye fixations are commonly used as indicators for the distribution of attention but research in OCD has revealed mixed results at best. Methodology/Principal Finding - Here we report atypical eye movement patterns in subclinical checkers during an ecologically valid working memory (WM) manipulation. Our key manipulation was to present an intermediate probe during the delay period of the memory task, explicitly asking for the location of a letter, which, however, had not been part of the encoding set (i.e., misleading participants). Using eye movement measures we now provide evidence that high checkers’ inhibitory impairments for misleading information results in them checking the contents of WM in an atypical manner. Checkers fixate more often and for longer when misleading information is presented than non-checkers. Specifically, checkers spend more time checking stimulus locations as well as locations that had actually been empty during encoding. Conclusions/Significance - We conclude that these atypical eye movement patterns directly reflect internal checking of memory contents and we discuss the implications of our findings for the interpretation of behavioural and neuropsychological data. In addition our results highlight the importance of ecologically valid methodology for revealing the impact of detrimental attention and memory checking on eye movement patterns.

How checking as a cognitive style influences working memory performance

Compulsive checking is known to influence memory, yet there is little consideration of checking as a cognitive style within the typical population. We employed a working memory task where letters had to be remembered in their locations. The key experimental manipulation was to induce repeated checking after encoding by asking about a stimulus that had not been presented. We recorded the effect that such misleading probes had on a subsequent memory test. Participants drawn from the typical population but who scored highly on a checking-scale had poorer memory and less confidence than low scoring individuals. While thoroughness is regarded as a quality, our results indicate that a cognitive style that favours repeated checking does not always lead to the best performance as it can undermine the authenticity of memory traces. This may affect various aspects of everyday life including the work environment and we discuss its implications and possible counter-measures. Copyright © 2010 John Wiley & Sons, Ltd.

Disturbing visual working memory:electrophysiological evidence for a role of the prefrontal cortex in recovery from interference

Single cell recordings in monkeys support the notion that the lateral prefrontal cortex (PFC) controls reactivation of visual working memory representations when rehearsal is disrupted. In contrast, recent fMRI findings yielded a double dissociation for PFC and the medial temporal lobe (MTL) in a letter working memory task. PFC was engaged in interference protection during reactivation while MTL was prominently involved in the retrieval of the letter representations. We present event-related potential data (ERP) that support PFC involvement in the top-down control of reactivation during a visual working memory task with endogenously triggered recovery after visual interference. A differentiating view is proposed for the role of PFC in working memory with respect to endogenous/exogenous control and to stimulus type. General implications for binding and retention mechanisms are discussed.

Threat-evoked anxiety disrupts spatial working memory performance:an attentional account

It is proposed that threat-evoked anxiety and spatial Working Memory (WM) rely on a common visuospatial attention mechanism. A prediction of this hypothesis is that spatial but not verbal WM should be disrupted in conditions of threat anxiety. Participants performed verbal and spatial n-back WM tasks in the presence or absence of threat of shock (shocks were not delivered). The presence of anxiety was assessed via heart rate recordings and self-report. Both measures clearly distinguished between WM blocks associated with threat of shock (Threat) and blocks, in which threat was absent (Safety). Performance on the spatial WM task was impaired in Threat relative to Safety. Furthermore, the more anxiety participants reported and the higher their heart rate in Threat compared to Safety, the more impaired was their spatial WM performance. This effect was not observed for verbal WM. The results indicate selective disruption of spatial WM performance by threat-evoked anxiety, interpreted in terms of more overlap in visuospatial attention between anxiety and spatial WM vs. anxiety and verbal WM.

Joint attention enhances visual working memory

Peer reviewed

Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility

We were supported by the Biotechnology and Biological Sciences Research Council grant BB/H001123/1 (P.W.), the Medical Research Council grants G0601498 and G1100546/2 (P.W.), Tenovus Scotland Grant G09/17 (A.J.M.) and the University of Aberdeen (P.W.). We thank O. Tüscher for discussion, P. Teismann and the microscopy core facility at the University of Aberdeen for the use of microscopy equipment, L. Strachan, A. Plano, S. Deiana for help with behavioral testing.

Memory-Based Attentional Guidance: A Window to the Relationship between Working Memory and Attention

Attention, the cognitive means by which we prioritize the processing of a subset of information, is necessary for operating efficiently and effectively in the world. Thus, a critical theoretical question is how information is selected. In the visual domain, working memory (WM)—which refers to the short-term maintenance and manipulation of information that is no longer accessible by the senses—has been highlighted as an important determinant of what is selected by visual attention. Furthermore, although WM and attention have traditionally been conceived as separate cognitive constructs, an abundance of behavioral and neural evidence indicates that these two domains are in fact intertwined and overlapping. The aim of this dissertation is to better understand the nature of WM and attention, primarily through the phenomenon of memory-based attentional guidance, whereby the active maintenance of items in visual WM reliably biases the deployment of attention to memory-matching items in the visual environment. The research presented here employs a combination of behavioral, functional imaging, and computational modeling techniques that address: (1) WM guidance effects with respect to the traditional dichotomy of top-down versus bottom-up attentional control; (2) under what circumstances the contents of WM impact visual attention; and (3) the broader hypothesis of a predictive and competitive interaction between WM and attention. Collectively, these empirical findings reveal the importance of WM as a distinct factor in attentional control and support current models of multiple-state WM, which may have broader implications for how we select and maintain information.

Is conscious awareness needed for all working memory processes?

Stein and colleagues argue there is no yet conclusive evidence for nonconscious working memory (WM) and that is critical to probe WM while ensuring null sensitivity to memory cues. While this stringent approach reduces the likelihood of nonconscious signaling for WM, we discuss existing work meeting this null sensitivity criteria, and, related work on nonconscious cognition in keeping with WM/awareness dissociations on the basis of a functional operational definition of WM. Further, because it is likely that WM is a nonunitary functional construct and visual awareness a gradual phenomenon, we propose that delineating the neural mechanisms for distinct WM types across different levels of awareness may prove the most fruitful approach for understanding the interplay between WM and consciousness.