Developmental differences in prefrontal activation during working memory maintenance and manipulation for different memory loads

The ability to keep information active in working memory is one of the cornerstones of cognitive development. Prior studies have demonstrated that regions which are important for working memory performance in adults, such as dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and superior parietal cortex, become increasingly engaged across school-aged development. The primary goal of the present functional MRI study was to investigate the involvement of these regions in the development of working memory manipulation relative to maintenance functions under different loads. We measured activation in DLPFC, VLPFC, and superior parietal cortex during the delay period of a verbal working memory task in 11-13-year-old children and young adults. We found evidence for age-related behavioral improvements in working memory and functional changes within DLPFC and VLPFC activation patterns. Although activation profiles of DLPFC and VLPFC were similar, group differences were most pronounced for right DLPFC. Consistent with prior studies, right DLPFC showed an interaction between age and condition (i.e. manipulation versus maintenance), specifically at the lower loads. This interaction was characterized by increased activation for manipulation relative to maintenance trials in adults compared to children. In contrast, we did not observe a significant age-dependent load sensitivity. These results suggest that age-related differences in the right DLPFC are specific to working memory manipulation and are not related to task difficulty and/or differences in short-term memory capacity.     

The effect of bicephalic stimulation of the dorsolateral prefrontal cortex on the attentional bias for threat: A transcranial direct current stimulation study

Previous stimulation studies demonstrated that the dorsolateral prefrontal cortex (DLPFC) is involved in threat processing. According to a model of emotional processing, an unbalance between the two DLPFCs, with a hyperactivation of right frontal areas, is involved in the processing of negative emotions and genesis of anxiety. In the present study, we investigated the role of the right and left DLPFC in threat processing in healthy women who also completed the State-Trait Anxiety Inventory (STAI). We simultaneously modulated the activity of the right and left dorsolateral prefrontal cortex by applying bicephalic transcranial direct current stimulation (tDCS) before participants completed a modified version of the classic Posner task using threatening and nonthreatening stimuli as spatial cues. Anodal stimulation on the right DLPFC with a simultaneous cathodal stimulation over the left side induced a disengagement bias in individuals with low STAI scores and a facilitation bias in individuals with high STAI scores. Anodal stimulation on the left DLPFC with the simultaneous cathodal stimulation over the right side did not affect threat processing. The findings of the present study provided specific support to the hypothesis that unbalanced activation between left and right hemispheres with enhanced activation of the right DLPFC is critical in early top-down threat processing in healthy individuals.     

Working memory load reduces the late positive potential and this effect is attenuated with increasing anxiety

Emotion regulation decreases the processing of arousing stimuli, as indexed by the late positive potential (LPP), an electrocortical component that varies in amplitude with emotional arousal. Emotion regulation increases activity in the prefrontal areas associated with cognitive control, including the dosolateral prefrontal cortex (DLPFC). The present study manipulated working memory load, known to activate the DLPFC, and recorded the LPP elicited by aversive and neutral IAPS pictures presented during the retention interval. The LPP was larger on low-load compared to high-load trials, and on trials with aversive compared to neutral pictures. These LPP data suggest that emotional content and working memory load have opposing effects on attention to distracting stimuli. State anxiety was associated with reduced modulation of the LPP by working memory load. Results are discussed in terms of competition for attention between emotion and cognition and suggest a relationship between DLPFC activation and the allocation of attentional resources to distracting visual stimuli–a relationship that may be disrupted with increasing anxiety.     

Age-related deficits in generation and manipulation of mental images: II. The role of dorsolateral prefrontal cortex.

The authors investigated neural substrates of age-related declines in mental imagery. Healthy adult participants (ages 19 to 77) performed a series of visual-spatial mental imagery tasks that varied in apparent difficulty and involved stimuli of varying graphic complexity. The volumes of the dorsolateral frontal cortex (DLPFC) and posterior visual processing areas were estimated from magnetic resonance imaging scans. The volume of the DLPFC and the fusiform cortex, working-memory capacity, and performance on the tasks involving image generation and manipulation were significantly reduced with age. Further analyses suggested that age-related deficits in performance on mental imagery tasks may stem in part from age-related shrinkage of the prefrontal cortex and age-related declines in working memory but not from age-related slowing of sensorimotor reaction time. The volume of cortical regions associated with modality-specific visual information processing did not show a consistent relationship with specific mental imagery processes.     

Recognition memory and prefrontal cortex: dissociating recollection and familiarity processes using rTMS

Recognition memory can be supported by both the assessment of the familiarity of an item and by the recollection of the context in which an item was encountered. The neural substrates of these memory processes are controversial. To address these issues we applied repetitive transcranial magnetic stimulation (rTMS) over the right and left dorsolateral prefrontal cortex (DLPFC) of healthy subjects performing a remember/know task. rTMS disrupted familiarity judgments when applied before encoding of stimuli over both right and left DLPFC. rTMS disrupted recollection when applied before encoding of stimuli over the right DLPFC. These findings suggest that the DLPFC plays a critical role in recognition memory based on familiarity as well as recollection.     

右侧背外侧前额叶在视觉工作记忆中的因果性作用

以往的影像学研究表明右侧背外侧前额叶皮层(DLPFC)在视觉工作记忆中发挥重要作用, 然而缺乏因果性的证据。本研究旨在考察右侧DLPFC的激活与视觉工作记忆容量的因果关系, 并探讨这一关系受到记忆负荷的调节及其神经机制。被试接受经颅直流电刺激之后完成视觉工作记忆变化检测任务, 根据被试在虚假刺激情况下从负荷4到负荷6任务记忆容量的增量将被试分为低记忆增长潜力组(简称低潜力组)和高记忆增长潜力组(简称高潜力组), 结果发现正性电刺激右侧DLPFC相对于虚假电刺激显著提升了高潜力组被试在低记忆负荷(负荷4)下的记忆容量及其对应的提取阶段的脑电指标SPCN成分。表明右侧DLPFC在视觉工作记忆的提取阶段发挥重要的因果性作用; 正性经颅直流电刺激右侧DLPFC可使工作记忆容量高潜力被试获得更多的脑活动增益, 并导致更好的行为提升效果。     

rTMS for PTSD: induced merciful oblivion or elimination of abnormal hypermnesia?

Neuroimaging studies and experimental data suggest that symptoms of posttraumatic stress disorder (PTSD) are associated with dysfunctions of neural circuits linking prefrontal cortex and the limbic system that have a role in autobiographic episodic memory. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) has been suggested to be beneficial to patients with PTSD, transiently alleviating re-experiencing as well as avoidance reactions and associated anxiety symptoms. In healthy humans, converging evidence suggests that rTMS of the right DLPFC interferes with episodic memory retrieval. Hence, we hypothesize that daily applications of rTMS in PTSD patients may reduce access to the set of autobiographical stored events, that, if re-experienced, may cause the overt PTSD symptoms.     

Subliminal food images compromise superior working memory performance in women with restricting anorexia nervosa

Prefrontal cortex (PFC) is dysregulated in women with restricting anorexia nervosa (RAN). It is not known whether appetitive non-conscious stimuli bias cognitive responses in those with RAN. Thirteen women with RAN and 20 healthy controls (HC) completed a dorsolateral PFC (DLPFC) working memory task and an anterior cingulate cortex (ACC) conflict task, while masked subliminal food, aversive and neutral images were presented. During the DLPFC task, accuracy was higher in the RAN compared to the HC group, but superior performance was compromised when subliminal food stimuli were presented: errors positively correlated with self-reported trait anxiety in the RAN group. These effects were not observed in the ACC task. Appetitive activation is intact and anxiogenic in women with RAN, and non-consciously interacts with working memory processes associated with the DLPFC. This interaction mechanism may underlie cognitive inhibition of appetitive processes that are anxiety inducing, in people with AN.     

Effects of tDCS over the right DLPFC on attentional disengagement from positive and negative faces: An eye-tracking study

The aim of this study was to increase insight in the neural substrates of attention processes involved in emotion regulation. The effects of right dorsolateral prefrontal cortex (i.e., DLPFC) stimulation on attentional processing of emotional information were evaluated. A novel attention task allowing a straightforward measurement of attentional engagement toward, and attentional disengagement away from emotional faces was used. A sample of healthy participants received 20 minutes of active and sham anodal transcranial direct current stimulation (i.e., tDCS) applied over the right DLPFC on 2 separate days and completed the attention task after receiving real or sham stimulation. Compared to sham stimulation, tDCS over the right DLPFC led to impairments in attentional disengagement from both positive and negative faces. Findings demonstrate a causal role of right DLPFC activity in the generation of attentional impairments that are implicated in emotional disturbances such as depression and anxiety.     

Trait motivation moderates neural activation associated with goal pursuit

Research has indicated that regions of left and right dorsolateral prefrontal cortex (DLPFC) are involved in integrating the motivational and executive function processes related to, respectively, approach and avoidance goals. Given that sensitivity to pleasant and unpleasant stimuli is an important feature of conceptualizations of approach and avoidance motivation, it is possible that these regions of DLPFC are preferentially activated by valenced stimuli. The present study tested this hypothesis by using a task in which goal pursuit was threatened by distraction from valenced stimuli while functional magnetic resonance imaging data were collected. The analyses examined whether the impact of trait approach and avoidance motivation on the neural processes associated with executive function differed depending on the valence or arousal level of the distractor stimuli. The present findings support the hypothesis that the regions of DLPFC under investigation are involved in integrating motivational and executive function processes, and they also indicate the involvement of a number of other brain areas in maintaining goal pursuit. However, DLPFC did not display differential sensitivity to valence.     

Neural mechanisms of spatial working memory: Contributions of the dorsolateral prefrontal cortex and the thalamic mediodorsal nucleus

The dorsolateral prefrontal cortex (DLPFC) has been known to play an important role in working memory. Neurophysiological studies have revealed that delay period activity observed in the DLPFC is a neural correlate of the temporary storage mechanism for information and that this activity represents either retrospective or prospective information, although the majority represents retrospective information. However, the DLPFC is not the only brain area related to working memory. The analysis of neural activity in the thalamic mediodorsal (MD) nucleus reveals that the MD also participates in working memory. Although similar task-related activities were observed in the MD, the directional bias of these activities and the proportion of presaccadic activity are different between the MD and the DLPFC. These results indicate that, although the MD participates in working memory, the way it participates in this process is different between these two areas, in that the MD participates more in motor control aspects than the DLPFC does.     

Remembering the time: a continuous clock

The neural mechanisms for time measurement are currently a subject of much debate. This article argues that our brains can measure time using the same dorsolateral prefrontal cells that are known to be involved in working memory. Evidence for this is: (1) the dorsolateral prefrontal cortex is integral to both cognitive timing and working memory; (2) both behavioural processes are modulated by dopamine and disrupted by manipulation of dopaminergic projections to the dorsolateral prefrontal cortex; (3) the neurons in question ramp their activity in a temporally predictable way during both types of processing; and (4) this ramping activity is modulated by dopamine. The dual involvement of these prefrontal neurons in working memory and cognitive timing supports a view of the prefrontal cortex as a multipurpose processor recruited by a wide variety of tasks.     

Persistent activity in the prefrontal cortex during working memory

The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in working memory. Notably, persistent activity in the DLPFC is often observed during the retention interval of delayed response tasks. The code carried by the persistent activity remains unclear, however. We critically evaluate how well recent findings from functional magnetic resonance imaging studies are compatible with current models of the role of the DLFPC in working memory. These new findings suggest that the DLPFC aids in the maintenance of information by directing attention to internal representations of sensory stimuli and motor plans that are stored in more posterior regions.     

背外侧前额叶对主动遗忘负性社会反馈的作用：针对抑郁症的TMS研究

抑郁症患者的负性心境可能源于其抑制功能障碍。患者在主动遗忘负性材料时无法有效调用背外侧前额叶(the dorsolateral prefrontal cortex, DLPFC)等负责抑制控制的额叶脑网络。同时, 患者对社会信息的加工比对非社会信息的加工存在更明显的认知神经障碍, 很难主动遗忘对自己不利的社会反馈信息。为了提高抑郁症患者对负性社会反馈的主动遗忘能力, 本研究采用经颅磁刺激技术(transcranial magnetic stimulation, TMS), 考察抑郁症患者在左侧(n = 32)或右侧DLPFC (n = 30)被激活后其记忆控制能力的改变。结果表明, 当患者的DLPFC被TMS激活时, 他们对社会拒绝的回忆正确率与健康对照组(n = 31)无差异, 且TMS激活右侧DLPFC还改善了患者对他人的社会态度。本研究是采用TMS提高抑郁症患者主动遗忘能力的首次尝试, 研究结果不但支持了DLPFC与记忆控制功能的因果关系, 还为临床治疗抑郁症、创伤后应激障碍、药物成瘾等患者的记忆控制缺陷提供了明确的神经靶点。     

Emotion-modulated performance and activity in left dorsolateral prefrontal cortex

Functional MRI (fMRI) was used to examine the relationship between processing of pleasant and unpleasant stimuli and activity in prefrontal cortex. Twenty volunteers identified the colors in which pleasant, neutral, and unpleasant words were printed. Pleasant words prompted more activity bilaterally in dorsolateral prefrontal cortex (DLPFC) than did unpleasant words. In addition, pleasant words prompted more activity in left than in right DLPFC. Response speed to pleasant words was correlated with DLPFC activity. These data directly link positive affect, enhanced performance, and prefrontal activity, providing some of the first fMRI evidence supporting models of emotional valence and frontal brain asymmetry based on electroencephalography (EEG).     

Prefrontal and hippocampal contributions to visual associative recognition: interactions between cognitive control and episodic retrieval

The ability to recover episodic associations is thought to depend on medial-temporal lobe mnemonic mechanisms and frontal lobe cognitive control processes. The present study examined the neural circuitry underlying non-verbal associative retrieval, and considered the consequences of successful retrieval on cognitive control demands. Event-related fMRI data were acquired while subjects retrieved strongly or weakly associated pairs of novel visual patterns in a two-alternative forced choice associative recognition paradigm. Behaviorally, successful retrieval of strongly associated relative to weakly associated pairs was more likely to be accompanied by conscious recollection of the pair's prior co-occurrence. At the neural level, right ventrolateral prefrontal cortex (VLPFC) and hippocampus were more active during successful retrieval of Strong than of Weak associations, consistent with a role in visual associative recollection. By contrast, Weak trials elicited greater activation in right anterior cingulate cortex (ACC), which may detect conflict between the similarly familiar target and foil stimuli in the absence of recollection. Consistent with this interpretation, stronger ACC activity was associated with weaker hippocampal and stronger right dorsolateral PFC (DLPFC) responses. Thus, recollection of relevant visual associations (hippocampus and VLPFC) results in lower levels of mnemonic conflict (ACC) and decreased familiarity-based monitoring demands (DLPFC). These findings highlight the interplay between cognitive control and episodic retrieval.     

Anxiety and cognitive efficiency: Differential modulation of transient and sustained neural activity during a working memory task

According to the processing-efficiency hypothesis (Eysenck, Derakshan, Santos, & Calvo, 2007), anxious individuals are thought to require greater activation of brain systems supporting cognitive control (e.g.,dorsolateral prefrontal cortex; DLPFC) in order to maintain equivalent performance to nonanxious subjects. A recent theory of cognitive control (Braver, Gray, & Burgess, 2007) has proposed that reduced cognitive efficiency might occur as a result of changes in the temporal dynamics of DLPFC recruitment. In this study, we used a mixed blocked/ event-related fMRI design to track transient and sustained activity in DLPFC while high- and low-anxious participants performed a working memory task. The task was performed after the participants viewed videos designed to induce neutral or anxiety-related moods. After the neutral video, the high-anxious participants had reduced sustained but increased transient activation in working memory areas, in comparison with low-anxious participants. The high-anxious group also showed extensive reductions in sustained activation of "default-network" areas (possible deactivation). After the negative video,the low-anxiety group shifted their activation dynamics in cognitive control regions to resemble those of the high-anxious group. These results suggest that reduced cognitive control in anxiety might be due to a transient, rather than sustained, pattern of working memory recruitment. Supplementary information for this study may be found at www.psychonomic.org/archive.     

The neurodevelopmental basis of math anxiety

Math anxiety is a negative emotional reaction to situations involving mathematical problem solving. Math anxiety has a detrimental impact on an individual's long-term professional success, but its neurodevelopmental origins are unknown. In a functional MRI study on 7- to 9-year-old children, we showed that math anxiety was associated with hyperactivity in right amygdala regions that are important for processing negative emotions. In addition, we found that math anxiety was associated with reduced activity in posterior parietal and dorsolateral prefrontal cortex regions involved in mathematical reasoning. Multivariate classification analysis revealed distinct multivoxel activity patterns, which were independent of overall activation levels in the right amygdala. Furthermore, effective connectivity between the amygdala and ventromedial prefrontal cortex regions that regulate negative emotions was elevated in children with math anxiety. These effects were specific to math anxiety and unrelated to general anxiety, intelligence, working memory, or reading ability. Our study identified the neural correlates of math anxiety for the first time, and our findings have significant implications for its early identification and treatment.     

Dorsolateral prefrontal cortex mediates working memory processes in motor skill learning

Neuroimaging studies have shown that the dorsolateral prefrontal cortex (DLPFC) is recruited during motor skill learning, which suggests the involvement of the DLPFC in working memory (WM) processes, such as selection and integration of motor representations temporarily stored in WM. However, direct evidence linking activation of the DLPFC to WM storage and manipulation during motor skill learning in real-time is rare. In this study, we conducted two experiments to investigate the causal role of DLPFC activity in WM storage and manipulation during motor skill learning under low and high WM-demand conditions. Participants received continuous theta burst stimulation (cTBS) and sham stimulation (crossover design) over the left DLPFC (experiment 1) or right DLPFC (experiment 2). Before and after stimulation, participants in both experiments performed a sequential finger-tapping (SFT) task containing repeated sequence (low-WM demand) and non-repeated sequence (high-WM demand) conditions which are used to study WM processes. The number of correct sequences (NoCS) and reproduction error rate were analyzed. Learning gains in NoCS improved significantly with the practice for both sequence types in the presence of either stimulation type. Compared to sham stimulation, cTBS over the left DLPFC resulted in significantly reduced learning gains in NoCS for non-repeated sequences. These results suggest that the left DLPFC contributes to WM manipulation during motor skill learning.     

rTMS stimulation on left DLPFC increases the correct recognition of memories for emotional target and distractor words

According to a recent hypothesis, the prefrontal cortex has been proposed as the site of emotional memory integration, because it is sensitive to the recognition of emotional contents. In the present research, we explored the role of the dorsolateral prefrontal cortex (DLPFC) in memory recognition processes for positive versus negative emotional stimuli when old (target) and new (distractor, either semantically related or unrelated to the target) stimuli were presented. The role of the DLPFC was analysed using an rTMS (repeated transcranial magnetic stimulation) paradigm that induced increased cortical activation of the left DLPFC. The subjects were required to perform a task that consisted of two experimental phases (i.e., an encoding and a recognition phase) in which the targets and the distractors were presented and recognition performance was measured. rTMS stimulation was provided over the left DLPFC during the recognition phase. We found that the rTMS stimulation affected the memory recognition of positive emotional material. Moreover, related and unrelated distractors were discarded better when they were positively valenced, and a more significant effect (i.e., increased performance) was produced in response to related distractors. This result suggests that the activation of the left DLPFC favours the memory recognition of positive emotional information, and that such activation is able to induce a more appropriate selective process to distinguish target from distractor stimuli in the presence of more complex processes (related distractors). The valence model of emotional cue processing may explain this increased performance by demonstrating the distinct role of the left hemisphere in the retrieval of positive emotional information.