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.     

Brain activations associated with shifts in response criterion on a recognition test.

Sensitivity and bias can be manipulated independently on a recognition test. The goal of this fMRI study was to determine whether neural activations associated with manipulations of a decision criterion would be anatomically distinct from neural activations associated with manipulations of memory strength and episodic retrieval. The results indicated that activations associated with shifting criteria (a manipulation of bias) were located in bilateral regions of the lateral cerebellum, lateral parietal lobe, and the dorsolateral prefrontal cortex extending from the supplementary motor area. These regions were anatomically distinct from activations in the prefrontal cortex produced during memory-based retrieval processes (manipulations of sensitivity), which tended to be more medial and anterior. These later activations are consistent with previous studies of episodic retrieval. Determining patterns of neural activations associated with decision-making processes relative to memory processes has important implications for Cognitive Neuroscience, including the use of these patterns to compare memory models in different paradigms.     

前额皮层肾上腺素能受体在工作记忆中的作用

前额皮层去甲肾上腺素能神经支配主要来自脑干蓝斑核。前额皮层存在不同类型的肾上腺素能受体。其中突触后α2及β2肾上腺素能受体的激活提高工作记忆;α1及β1肾上腺素能受体的激活损害工作记忆。不同受体是通过激活不同的信号通路发挥对工作记忆的调节作用。来自人类被试的研究结果与对动物的研究结果之间尚存在不一致。了解前额皮层不同肾上腺素受体的作用为开发治疗与前额皮层功能失调相关疾病的药物提供了新的方向。     

Large-scale neural network for sentence processing

Our model of sentence comprehension includes at least grammatical processes important for structure-building, and executive resources such as working memory that support these grammatical processes. We hypothesized that a core network of brain regions supports grammatical processes, and that additional brain regions are activated depending on the working memory demands associated with processing a particular grammatical feature. We used functional magnetic resonance imaging (fMRI) to test this hypothesis by comparing cortical activation patterns during coherence judgments of sentences with three different syntactic features. We found activation of the ventral portion of left inferior frontal cortex during judgments of violations of each grammatical feature. Increased recruitment of the dorsal portion of left inferior frontal cortex was seen during judgments of violations of specific grammatical features that appear to involve a more prominent working memory component. Left posterolateral temporal cortex and anterior cingulate were also implicated in judging some of the grammatical features. Our observations are consistent with a large-scale neural network for sentence processing that includes a core set of regions for detecting and repairing several different kinds of grammatical features, and additional regions that appear to participate depending on the working memory demands associated with processing a particular grammatical feature.     

Right amygdalar and temporofrontal activation during autobiographic, but not during fictitious memory retrieval

What distinguishes the recall of real-life experiences from that of self-created, fictitious emotionally laden information? Both kinds of information belong to the episodic memory system. Autobiographic memories constitute that part of the episodic memory system that is composed of significant life episodes, primarily of the distant past. Functional imaging was used to study the neural networks engaged in retrieving autobiographic and fictitious information of closely similar content. The principally activated brain regions overlapped considerably and constituted temporal and inferior prefrontal regions plus the cerebellum. Selective activations of the right amygdala and the right ventral prefrontal cortex (at the level of the uncinate fascicle interconnnecting prefrontal and temporopolar areas) were found when subtracting fictitious from autobiographic retrieval. Furthermore, distinct foci in the left temporal lobe were engaged. These data demonstrate that autobiographic memory retrieval uses (at least in non-brain damaged individuals) a network of right hemispheric ventral prefrontal and temporopolar regions and left hemispheric lateral temporal regions. It is concluded that it is the experiential character, its special emotional infiltration and its arousal which distinguishes memory of real-life from that of fictitious episodes. Consequently, our results point to the engagement of a bi-hemispheric network in which the right temporo-prefrontal hemisphere is likely to be responsible for the affective/arousal side of information retrieval and the left-hemispheric temporal gyrus for its engram-like representation. Portions of the neural activation found during retrieval might, however, reflect re-encoding processes as well.     

Integrating orbitofrontal cortex into prefrontal theory: common processing themes across species and subdivisions

Currently, many theories highlight either representational memory or rule representation as the hallmark of prefrontal function. Neurophysiological findings in the primate dorsolateral prefrontal cortex indicate that both features may characterize prefrontal processing. Neurons in the dorsolateral prefrontal cortex encode information in working memory, and this information is represented when relevant to the rules governing performance in a task. In this review, we discuss recent reports of encoding in primate and rat orbitofrontal regions indicating that these features also characterize activity in the orbitofrontal subdivision of the prefrontal cortex. These data indicate that (1) neural activity in the orbitofrontal cortex links the current incentive value of reinforcers to cues, rather than representing the physical features of cues or associated reinforcers; (2) this incentive-based information is represented in the orbitofrontal cortex when it is relevant to the rules guiding performance in a task; and (3) incentive information is also represented in the orbitofrontal cortex in working memory during delays when neither the cues nor reinforcers are present. Therefore, although the orbitofrontal cortex appears to be uniquely specialized to process incentive or motivational information, it may be integrated into a more global framework of prefrontal function characterized by representational encoding of performance-relevant information.     

Distinguishing the neural correlates of episodic memory encoding and semantic memory retrieval

Episodic memory and semantic memory interact very closely. In particular, episodic memory encoding (EE) tends to elicit semantic memory retrieval (SR), and vice versa. Thus, similar activations for EE and SR in functional neuroimaging studies may reflect shared memory processes, or they may reflect the fact that EE and SR are usually confounded. To address this issue, we used a factorial functional magnetic resonance imaging approach to disentangle the neural correlates of EE and SR. Within the left temporal lobe, the hippocampus was associated with successful EE, whereas a posterior lateral region was associated with successful SR. Within the left inferior prefrontal cortex, a posterior region was involved in SR, a mid region was involved in both SR and EE, and an anterior region was involved in EE, but only when SR was also high. Thus, the neural correlates of EE and SR are dissociable but interact in specific brain regions.     

Alterations in working memory networks in amnestic mild cognitive impairment

Patients with amnestic mild cognitive impairment (aMCI) show preserved or mildly impaired working memory, despite their deficits in episodic memory. We aimed to identify performance and/or neural differences between aMCI patients and matched controls on a standard working memory fMRI task. Neuropsychological assessment demonstrated aMCI impairments in verbal and visual episodic long-term memory, with intact IQ and executive function. Participants completed a standard three-level N-back task where patients were unimpaired. Functional activations in the control group were found in expected areas, including the inferior parietal lobule and dorsolateral prefrontal cortex. Group differences were found in the insula and lingual gyrus and, in a region of interest analysis, in the hippocampus. In all cases, these were caused by an absence of task-related deactivations in the aMCI group. The results are consistent with reports of failure in task-related deacivations in aMCI and could be early indications of pathology.     

Neuroimaging evidence for agenda-dependent monitoring of different features during short-term source memory tests

A short-term source monitoring procedure with functional magnetic resonance imaging assessed neural activity when participants made judgments about the format of 1 of 4 studied items (picture, word), the encoding task performed (cost, place), or whether an item was old or new. The results support findings from long-term memory studies showing that left anterior ventrolateral prefrontal cortex (PFC) is engaged when people make source attributions about reflectively generated information (cognitive operations, conceptual features). The findings also point to a role for right lateral PFC in attention to perceptual features and/or familiarity in making source decisions. Activity in posterior regions also differed depending on what was evaluated. These results provide neuroimaging evidence for theoretical approaches emphasizing that agendas influence which features are monitored during remembering (e.g., M. K. Johnson, S. Hashtroudi, & D. S. Lindsay, 1993). They also support the hypothesis that some of the activity in left lateral PFC and posterior regions associated with remembering specific information is not unique to long-term memory but rather is associated with agenda-driven source monitoring processes common to working memory and long-term memory.     

客体与空间工作记忆的分离：来自皮层慢电位的证据

利用128导事件相关电位技术,采用延迟匹配任务的实验范式,测查了16名正常被试在完成客体任务和空间任务时的皮层慢电位（slow cortical potentials,简称sp成分）,实验发现：在后部脑区,客体工作记忆与空间工作记忆在慢波活动的时间上存在分离,空间任务更早的诱发出负sp成分,并且空间任务激活更多的后部脑区;左下前额叶在客体工作记忆任务与空间工作记忆任务中都有激活,并且激活强度不存在显著差异;背侧前额叶主要负责客体信息的保持与复述,但左右背侧前额叶的激活强度存在不对称性。     

Updating working memory in aircraft noise and speech noise causes different fMRI activations

The present study used fMRI/BOLD neuroimaging to investigate how visual‐verbal working memory is updated when exposed to three different background‐noise conditions: speech noise, aircraft noise and silence. The number‐updating task that was used can distinguish between “substitution processes,” which involve adding new items to the working memory representation and suppressing old items, and “exclusion processes,” which involve rejecting new items and maintaining an intact memory set. The current findings supported the findings of a previous study by showing that substitution activated the dorsolateral prefrontal cortex, the posterior medial frontal cortex and the parietal lobes, whereas exclusion activated the anterior medial frontal cortex. Moreover, the prefrontal cortex was activated more by substitution processes when exposed to background speech than when exposed to aircraft noise. These results indicate that (a) the prefrontal cortex plays a special role when task‐irrelevant materials should be denied access to working memory and (b) that, when compensating for different types of noise, either different cognitive mechanisms are involved or those cognitive mechanisms that are involved are involved to different degrees.     

工作记忆与情景记忆中脑区的重合与分离——从脑区定位看两者关系

尽管近期的研究结果认为前额叶在工作记忆和情景记忆任务中均被激活,但是仍然不清楚是否有特定的区域对两种记忆起着不同作用。对于工作记忆和情景记忆在脑区上的重合,研究者们做出了不同的解释。某些研究者认为脑区的重合反映了包含于情景记忆中的工作记忆的作用,另一些研究者则认为这种重合反映的是与工作记忆和情景记忆都有关的反省过程的性质。对此,作者提出了相应的讨论意见。     

Evidence for working memory storage operations in perceptual cortex

Isolating the short-term storage component of working memory (WM) from the myriad of associated executive processes has been an enduring challenge. Recent efforts have identified patterns of activity in visual regions that contain information about items being held in WM. However, it remains unclear (1) whether these representations withstand intervening sensory input and (2) how communication between multimodal association cortex and the unimodal perceptual regions supporting WM representations is involved in WM storage. We present evidence that the features of a face held in WM are stored within face-processing regions, that these representations persist across subsequent sensory input, and that information about the match between sensory input and a memory representation is relayed forward from perceptual to prefrontal regions. Participants were presented with a series of probe faces and indicated whether each probe matched a target face held in WM. We parametrically varied the feature similarity between the probe and target faces. Activity within face-processing regions scaled linearly with the degree of feature similarity between the probe face and the features of the target face, suggesting that the features of the target face were stored in these regions. Furthermore, directed connectivity measures revealed that the direction of information flow that was optimal for performance was from sensory regions that stored the features of the target face to dorsal prefrontal regions, supporting the notion that sensory input is compared to representations stored within perceptual regions and is subsequently relayed forward. Together, these findings indicate that WM storage operations are carried out within perceptual cortex.     

Neural bases of focusing attention in working memory: An fMRI study based on group differences

Using fMRI, we investigated neural substrates for focusing attention in working memory. To explore this focusing effect, two kinds of reading span test (RST), focused and nonfocused, were performed. In the focused RST (F-RST), the target word to be maintained was the focus word in the sentence. In the nonfocused RST (NF-RST), the target word was not the focus word in the sentence. In both RST conditions, significant activations were found in three main regions: left dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and left superior parietal lobule (SPL). In addition, fMRI signal changes increased in the left SPL in the NF-RST condition. These findings suggest that the neural substrates of focusing attention are based on SPL and ACC-DLPFC networks. Furthermore, there were group differences in the focusing effect between high-span and low-span subjects: High-span subjects showed focusing effects (supported by SPL control) greater than those of low-span subjects.     

The neural bases of the effects of item-nonspecific proactive interference in working memory

We reanalyzed the behavioral and fMRI data from seven previously published studies of working memory in order to assess the behavioral and neural effects of item-nonspecific proactive interference (PI; attributable to the accrual of antecedent information independent of the repetition of particular items). We hypothesized that item-nonspecific PI, implicated in age-related declines in working memory performance, is mediated by the same mechanism(s) that mediate item-specific PI (occurring when an invalid memory probe matches a memorandum from the previous trial). Reaction time increased across trials as a function of position within the block, a trend that reversed across the duration of each multiblock experiment. The fMRI analyses revealed sensitivity to item-nonspecific PI during the probe epoch in the left anterior inferior frontal gyrus and the left dorsolateral prefrontal cortex (PFC). They also revealed a negative trend, across trials, in the transient probe-evoked component of the global signal. A common PFC-based mechanism may mediate many forms of PI.     

Age-Related Changes in Neural Activation During Working Memory Performance

Changes in frontal lobe functions are a typical part of aging of the brain. There are age-related declines in working memory performance, a skill requiring frontal lobe activation. This study examined neural activation, using [15 O] water positron emission tomography (PET) methodology, during performance on two verbal working memory tasks in younger and older participants. The results demonstrated the typical areas of activation associated with working memory performance (e.g., dorsolateral prefrontal cortex and inferior parietal cortex) in both groups. However, the younger participants utilized the right dorsolateral prefrontal cortex and anterior cingulate gyrus significantly more than the older participants. In turn, the older participants used the left dorsolateral prefrontal cortex significantly more than the younger participants and maintained material-specific lateralization in their pattern of activation. These findings are consistent with a previous report of different age-related patterns of frontal activation during working memory.     

Toward neuroanatomical models of analogy: a positron emission tomography study of analogical mapping

Several brain regions associated with analogical mapping were identified using (15)O-positron emission tomography with 12 normal, high intelligence adults. Each trial presented during scanning consisted of a source picture of colored geometric shapes, a brief delay, and a target picture of colored geometric shapes. Analogous pictures did not share similar geometric shapes but did share the same system of abstract visuospatial relations. Participants judged whether each source-target pairing was analogous (analogy condition) or identical (literal condition). The results of the analogy-literal comparison showed activation in the dorsomedial frontal cortex and in the left hemisphere; the inferior, middle, and medial frontal cortices; the parietal cortex; and the superior occipital cortex. Based on these results as well as evidence from relevant cognitive neuroscience studies of reasoning and of executive working memory, we hypothesize that analogical mapping is mediated by the left prefrontal and inferior parietal cortices.     

Aging effects on memory encoding in the frontal lobes

Functional magnetic resonance imaging (fMRI) was used to compare frontal-lobe activation in younger and older adults during encoding of words into memory. Participants made semantic or nonsemantic judgments about words. Younger adults exhibited greater activation for semantic relative to nonsemantic judgments in several regions, with the largest activation in the left inferior frontal gyrus. Older adults exhibited greater activation for semantic judgments in the same regions. but the extent of activation was reduced in left prefrontal regions. In older adults, there was a significant association between behavioral tests of declarative and working memory and extent of frontal activation. These results suggest that age-associated decreases in memory ability may be due to decreased frontal-lobe contributions to the initial encoding of experience.     

Distinct prefrontal molecular mechanisms for information storage lasting seconds versus minutes

The prefrontal cortex (PFC) is known to actively hold information "online" for a period of seconds in working memory for guiding goal-directed behavior. It has been proposed that relevant information is stored in other brain regions, which is retrieved and held in working memory for subsequent assimilation by the PFC in order to guide behavior. It is uncertain whether PFC stores information outside the temporal limits of working memory. Here, we demonstrate that although enhanced cAMP-dependent protein kinase A (PKA) activity in the PFC is detrimental to working memory, it is required for performance in tasks involving conflicting representations when memory storage is needed for minutes. This study indicates that distinct molecular mechanisms within the PFC underlie information storage for seconds (working memory) and for minutes (short-term memory). In addition, our results demonstrate that short-term memory storage within the prefrontal cortex is required for guiding behavior in tasks with conflicts and provides a plausible mechanism by which the prefrontal cortex executes cognitive control.     

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.