Working memory retention systems: a state of activated long-term memory

High temporal resolution event-related brain potential and electroencephalographic coherence studies of the neural substrate of short-term storage in working memory indicate that the sustained coactivation of both prefrontal cortex and the posterior cortical systems that participate in the initial perception and comprehension of the retained information are involved in its storage. These studies further show that short-term storage mechanisms involve an increase in neural synchrony between prefrontal cortex and posterior cortex and the enhanced activation of long-term memory representations of material held in short-term memory. This activation begins during the encoding/comprehension phase and evidently is prolonged into the retention phase by attentional drive from prefrontal cortex control systems. A parsimonious interpretation of these findings is that the long-term memory systems associated with the posterior cortical processors provide the necessary representational basis for working memory, with the property of short-term memory decay being primarily due to the posterior system. In this view, there is no reason to posit specialized neural systems whose functions are limited to those of short-term storage buffers. Prefrontal cortex provides the attentional pointer system for maintaining activation in the appropriate posterior processing systems. Short-term memory capacity and phenomena such as displacement of information in short-term memory are determined by limitations on the number of pointers that can be sustained by the prefrontal control systems.     

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.     

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。     

A role for prefrontal calcium-sensitive protein phosphatase and kinase activities in working memory

The prefrontal cortex is involved in the integration and interpretation of information for directing thoughts and planning action. Working memory is defined as the active maintenance of information in mind and is thought to lie at the core of many prefrontal functions. Although dopamine and other neurotransmitters have been implicated, the intracellular events activated by their receptors that influence working memory are poorly understood. We demonstrate that working memory involves transient changes in prefrontal G(q/11)-signaling and in calcium-dependent intracellular protein phosphatase and kinase activity. Interestingly, inhibition of the calcium activated phosphatase calcineurin impaired, while calcium/calmodulin dependent kinase II (CaMKII) and calcium-dependent protein kinase C (PKC) enhanced, working memory. Our findings suggest that the active maintenance of information required for working memory involves transient changes in the balance of these enzymes' activities.     

Neural Bases of Human Working Memory

Working memory is the memory system that allows us to briefly keep information active, often so we can operate on it. Studies with rhesus monkeys first established that this system is partly mediated by neural mechanisms in the prefrontal cortex. Recently, there has been a substantial effort to study the neural bases of working memory in humans, using neuroimaging techniques such as positron emission tomography and functional magnetic resonance imaging. Some of the initial neuroimaging studies with humans focused on the neural mechanisms that mediate our ability to keep spatial information active. These results indicated that human spatial working memory is partly mediated by regions in parietal and prefrontal cortex. Subsequent research has shown that a different neural system is involved when people store object (rather than spatial) information, a difference similar to that found in monkeys.     

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 primate working memory networks

Working memory has long been associated with the prefrontal cortex, since damage to this brain area can critically impair the ability to maintain and update mnemonic information. Anatomical and physiological evidence suggests, however, that the prefrontal cortex is part of a broader network of interconnected brain areas involved in working memory. These include the parietal and temporal association areas of the cerebral cortex, cingulate and limbic areas, and subcortical structures such as the mediodorsal thalamus and the basal ganglia. Neurophysiological studies in primates confirm the involvement of areas beyond the frontal lobe and illustrate that working memory involves parallel, distributed neuronal networks. In this article, we review the current understanding of the anatomical organization of networks mediating working memory and the neural correlates of memory manifested in each of their nodes. The neural mechanisms of memory maintenance and the integrative role of the prefrontal cortex are also discussed.     

振动触觉频率信息的工作记忆容量及存储机制

工作记忆可以同时保存多个信息并且容量有限, 这一内在机制是工作记忆研究的重点问题。视觉和言语等研究领域都发现工作记忆能够存储多个信息单元, 但对振动触觉工作记忆是否能存储多个频率信息目前尚无相关研究。由于振动触觉频率刺激和视觉刺激具有不同的神经编码机制, 以及振动频率信息是通过躯体感觉产生的模拟的、单维的、参数化信息, 振动触觉工作记忆容量及其加工存储机制的研究也必不可少。首先, 本项目将采用新的实验范式, 探究不同的刺激呈现方式以及不同反应报告方式下, 振动触觉工作记忆的容量及其认知机制。其次, 本项目也将同时运用功能磁共振成像(fMRI)技术, 来阐述振动触觉工作记忆加工存储的神经机制。探究基于触觉频率信息的参数工作记忆容量及其神经机制是完善工作记忆模型的重要补充, 将有助于提高我们对工作记忆系统的理解, 并为视觉、听觉、触觉多模态感知觉信息的跨通道研究奠定基础。     

Neurobıology of Repressıon: A Hypothetıcal Interpretatıon

Freud lived in a time when technology was incapable of explaining the biological correlates of the mental processes he described in psychoanalytic theory. During the last two decades, advances in neuroimaging methods and neuroscience have provided new insights for understanding mind-brain collaboration. Neurobiological underpinnings of psychoanalytical concepts have been an area of interest in recent years. This paper will suggest a new hypothesis for neurobiology of repression. This hypothesis will be discussed with the help of our knowledge about neurobiological mechanisms underlying perception of the emotional significance of an event, memory formation of an emotionally arousing stimulus, role of prefrontal cortex in modulation of subcortical information, neural mechanisms of suppression and molecular mechanisms of memory erasure. We suggest that dorsolateral prefrontal cortex, and especially its caudal part plays a major role for repression of childhood traumatic events. Possible molecular mechanism of memory erasure in repression is long term depression of glutamatergic neurotransmission between prefrontal cortex- thalamus- limbic system.     

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.     

Neural correlates of learning and working memory in the primate posterior parietal cortex

The posterior parietal cortex has been traditionally associated with coordinate transformations necessary for interaction with the environment and with visual-spatial attention. More recently, involvement of posterior parietal cortex in other cognitive functions such as working memory and task learning has become evident. Neurophysiological experiments in non-human primates and human imaging studies have revealed neural correlates of memory and learning at the single neuron and at the brain network level. During working memory, posterior parietal neurons continue to discharge and to represent stimuli that are no longer present. This activation resembles the responses of prefrontal neurons, although important differences have been identified in terms of the ability to resist stimulation by distracting stimuli, which is more evident in the prefrontal than the posterior parietal cortex. Posterior parietal neurons also become active during tasks that require the organization of information into larger structured elements and their activity is modulated according to learned context-dependent rules. Neural correlates of learning can be observed in the mean discharge rate and spectral power of neuronal spike trains after training to perform new task sets or rules. These findings demonstrate the importance of posterior parietal cortex in brain networks mediating working memory and learning.     

Neurocognitive Contributions to Motor Skill Learning: The Role of Working Memory

ABSTRACT

Researchers have begun to delineate the precise nature and neural correlates of the cognitive processes that contribute to motor skill learning. The authors review recent work from their laboratory designed to further understand the neurocognitive mechanisms of skill acquisition. The authors have demonstrated an important role for spatial working memory in 2 different types of motor skill learning, sensorimotor adaptation and motor sequence learning. They have shown that individual differences in spatial working memory capacity predict the rate of motor learning for sensorimotor adaptation and motor sequence learning, and have also reported neural overlap between a spatial working memory task and the early, but not late, stages of adaptation, particularly in the right dorsolateral prefrontal cortex and bilateral inferior parietal lobules. The authors propose that spatial working memory is relied on for processing motor error information to update motor control for subsequent actions. Further, they suggest that working memory is relied on during learning new action sequences for chunking individual action elements together.     

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.     

Learning representations in a gated prefrontal cortex model of dynamic task switching

The prefrontal cortex is widely believed to play an important role in facilitating people's ability to switch performance between different tasks. We present a biologically‐based computational model of prefrontal cortex (PFC) that explains its role in task switching in terms of the greater flexibility conferred by activation‐based working memory representations in PFC, as compared with more slowly adapting weight‐based memory mechanisms. Specifically we show that PFC representations can be rapidly updated when a task switches via a dynamic gating mechanism based on a temporal‐differences reward‐prediction learning mechanism. Unlike prior models of this type, the present model develops all of its internal representations via learning mechanisms as shaped by the demands of continuous periodic task switching. This advance opens up a new domain of research into the interactions between working memory task demands and the representations that develop to meet them. Results on a version of the Wisconsin card sorting task are presented for the full model and a number of comparison networks that test the importance of various model features. Furthermore, we show that a lesioned model produces perseverative errors like those seen in frontal patients.     

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.     

Attention and cognitive control as emergent properties of information representation in working memory

A hallmark of primate, and particularly human, behavior is cognitive control, the ability to integrate information from a multitude of sources and use that information to flexibly guide behavior in order to achieve an infinite number of goals. The neural mechanisms of cognitive control have yet to be fully elucidated, although the prefrontal cortex is known to play a critical role. Here, I review evidence suggesting that a unifying principle regarding the role of various portions of the prefrontal cortex in a wide range of cognitive tasks is the active maintenance in working memory of different types of currently relevant information-from specific stimulus features, to instructional cues, to motivational goals and contexts. I argue that the key to demonstrating the existence of this domain-dependent organization lies in a better understanding of the nature of the representation of this information and the ways in which this information itself controls cognition and behavior.     

Evidence for neocortical involvement in reference memory

Rats were trained on an eight-arm radial maze task using a procedure that provides for an assessment of both working and reference memory. Following training, rats received parietal cortex, medial prefrontal cortex, visual cortex, or nucleus basalis magnocellularis lesions. Rats with visual cortex lesions showed no change in performance on either working or reference memory. Rats with parietal cortex lesions displayed a temporary deficit in reference, but no deficit on working memory. Animals with medial prefrontal cortex lesions showed a temporary deficit on both working and reference memory. Rats with extensive lateral frontal and parietal cortex depletion of acetylcholinesterase following nucleus basalis magnocellularis lesions had a marked disruption only of reference but not of working memory. It is concluded that neocortex and possibly the cholinergic projections to neocortex play an important role in mediating reference memory.     

Neuroanatomical correlates of processing in visual and visuospatial working memory

Working memory is traditionally seen as being organised in a modular way with a central executive orchestrating at least two slave systems (phonological loop and visuospatial sketch pad). Neuroanatomical correlates of the visual and visuospatial subsystems and the central executive are discussed in this article. A series of experiments are presented yielding evidence for a differentiation into active and passive processing in working memory as well as their neuroanatomical correlates in the prefrontal cortex. Data, yielding evidence for an interaction and separation of visual and visuospatial working memory are presented and discussed. Further results are presented which suggest a convergence of these two systems with increasing working memory demands. The discussed findings will give new insight in the organisation of visual and visuospatial working memory on the anatomical level.     

Working memory, short-term memory, and general fluid intelligence: a latent-variable approach.

A study was conducted in which 133 participants performed 11 memory tasks (some thought to reflect working memory and some thought to reflect short-term memory), 2 tests of general fluid intelligence, and the Verbal and Quantitative Scholastic Aptitude Tests. Structural equation modeling suggested that short-term and working memories reflect separate but highly related constructs and that many of the tasks used in the literature as working memory tasks reflect a common construct. Working memory shows a strong connection to fluid intelligence, but short-term memory does not. A theory of working memory capacity and general fluid intelligence is proposed: The authors argue that working memory capacity and fluid intelligence reflect the ability to keep a representation active, particularly in the face of interference and distraction. The authors also discuss the relationship of this capability to controlled attention, and the functions of the prefrontal cortex.     

Neural mediation of memory for time: Role of the hippocampus and medial prefrontal cortex

Within the context of the neurobiology of attribute model, memory for the temporal attribute is composed of at least three features—memory for duration, memory for succession, or temporal order, and memory for past and future time perspective within a dual-based (data and knowledge) memory system. Research aimed at testing the assumption that the hippocampus and interconnected neural circuits mediate the temporal attribute within the data-based memory system and the prefrontal cortex and interconnected neural circuits mediate the temporal attribute within the knowledge-based memory system in animals and humans is reviewed. The research indicates that (1) memory for the duration feature of the temporal attribute is mediated by the hippocampus, but not prefrontal cortex, in both animals and humans, (2) memory for the temporal order feature of the temporal attribute based on new information is subserved by both the hippocampus and the prefrontal cortex, but that based on prior knowledge or the ability to use prior knowledge is supported only by prefrontal cortex, and not the hippocampus, in both animals and humans, and (3) memory for the past (time perspective) feature of the temporal attribute is mediated by the hippocampus, whereas memory for the future (time perspective) feature of the temporal attribute is supported by the prefrontal cortex in both animals and humans. There is a clear parallel between animals and humans in terms of hippocampal and prefrontal cortex mediation of the temporal attribute, supporting the assumption of evolutionary continuity. There is support for a greater involvement of the hippocampus in comparison with the prefrontal cortex in mediating temporal attribute information within the data-based memory system. Conversely, there is support for a greater involvement of the prefrontal cortex in comparison with the hippocampus in mediating temporal attribute information within the knowledge-based memory system. Future research needs to concentrate on the development of new paradigms to measure memory for different temporal features and to uncover the critical neural circuits that subserve these temporal features.