The role of spatial configuration in tests of working memory explored with functional neuroimaging

While the importance of the prefrontal cortex for "higher-order" cognitive functions is largely undisputed, no consensus has been reached regarding the fractionation of functions within this region. Several recent functional neuroimaging studies have suggested that the mid-ventrolateral frontal cortex may play an important role in various aspects of human memory. Thus, similar patterns of activation have been observed in this region during analogous spatial, verbal and visual span tasks. In the present study, however, activation was observed in a more dorsolateral region of the lateral frontal cortex during a modified version of the spatial span task, which differed only in the spatial configuration of the array employed. The results of a supplementary behavioral study, designed to investigate this effect further, suggest that in spatial memory tasks certain stimulus configurations may encourage subjects to adopt mnemonic strategies, which may depend upon dorsolateral, rather than ventrolateral, regions of the frontal cortex. These findings shed further light on the functional relationship between dorsal and ventral regions of the lateral frontal cortex and, more specifically, how the "executive" processes assumed to be dependent upon these regions might contribute to aspects of human memory.     

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.     

Common fronto-parietal activity in attention, memory, and consciousness: shared demands on integration?

Fronto-parietal activity has been frequently observed in fMRI and PET studies of attention, working memory, and episodic memory retrieval. Several recent fMRI studies have also reported fronto-parietal activity during conscious visual perception. A major goal of this review was to assess the degree of anatomical overlap among activation patterns associated with these four functions. A second goal was to shed light on the possible cognitive relationship of processes that relate to common brain activity across functions. For all reviewed functions we observed a consistent and overlapping pattern of brain activity. The overlap was most pronounced for the bilateral parietal cortex (BA 7 and BA 40; close to the intraparietal sulcus), and dorsolateral prefrontal cortex (right BA 9 and left BA 6). The common fronto-parietal activity will be discussed in terms of processes related to integration of distributed representations in the brain.     

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.     

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.     

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.     

Domain-dependent activation during spatial and nonspatial auditory working memory

Visual system has been proposed to be divided into two, the ventral and dorsal, processing streams. The ventral pathway is thought to be involved in object identification whereas the dorsal pathway processes information regarding the spatial locations of objects and the spatial relationships among objects. Several studies on working memory (WM) processing have further suggested that there is a dissociable domain-dependent functional organization within the prefrontal cortex for processing of spatial and nonspatial visual information. Also the auditory system is proposed to be organized into two domain-specific processing streams, similar to that seen in the visual system. Recent studies on auditory WM have further suggested that maintenance of nonspatial and spatial auditory information activates a distributed neural network including temporal, parietal, and frontal regions but the magnitude of activation within these activated areas shows a different functional topography depending on the type of information being maintained. The dorsal prefrontal cortex, specifically an area of the superior frontal sulcus (SFS), has been shown to exhibit greater activity for spatial than for nonspatial auditory tasks. Conversely, ventral frontal regions have been shown to be more recruited by nonspatial than by spatial auditory tasks. It has also been shown that the magnitude of this dissociation is dependent on the cognitive operations required during WM processing. Moreover, there is evidence that within the nonspatial domain in the ventral prefrontal cortex, there is an across-modality dissociation during maintenance of visual and auditory information. Taken together, human neuroimaging results on both visual and auditory sensory systems support the idea that the prefrontal cortex is organized according to the type of information being maintained in WM.     

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.     

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 neural basis of updating: Distinguishing substitution processes from other concurrent processes

Sörqvist, P. & Sætrevik, B. (2010). The neural basis of updating: Distinguishing substitution processes from other concurrent processes. Scandinavian Journal of Psychology, 51, 357–362. Most previous studies of updating processes have not been able to contrast processes of substituting items in memory with other concurrent processes. In the present investigation, we used a new task called “number updating” and an fMRI protocol to contrast the activation of trials that require item substitution (adding a new item to the working memory representation and suppressing an old item) with trials that involve no substitution (discarding the new item). Trials that require item substitution activated the dorsolateral prefrontal cortex, the posterior medial frontal cortex and the parietal lobes, areas typically seen activated for working memory tasks in general. Trials that do not require substitution activated the anterior medial frontal cortex. Studies examining executive functions have associated this area with cognitive conflict, and may represent suppression of the substitution processes.     

An analysis of rat prefrontal cortex in mediating executive function

While it is acknowledged that species specific differences are an implicit condition of comparative studies, rodent models of prefrontal function serve a significant role in the acquisition of converging evidence on prefrontal function across levels of analysis and research techniques. The purpose of the present review is to examine whether the prefrontal cortex (PFC) in rats supports a variety of processes associated with executive function including working memory, temporal processing, planning (prospective coding), flexibility, rule learning, and decision making. Therefore, in this review we examined changes associated with working memory processes for spatial locations, visual objects, odors, tastes, and response domains or attributes, temporal processes including temporal order, sequence learning, prospective coding, behavioral flexibility associated with reversal learning and set shifting, paired associate learning, and decision making based on effort, time discounting, and uncertainty following damage to the PFC in rats. In addition, potential parallel processes of executive function in monkeys and humans based on several theories of subregional differentiation within the PFC will be presented. Specifically, theories based on domain or attribute specificity (Goldman-Rakic, 1996), level of processing (Petrides, 1996), rule learning based on complexity (Wise, Murray, & Gerfen, 1996), executive functions based on connectivity with other brain regions associated with top-down control (Miller & Cohen, 2001), are presented and applied to PFC function in rats with the aim of understanding subregional specificity in the rat PFC. The data suggest that there is subregional specificity within the PFC of rats, monkey and humans and there are parallel cognitive functions of the different subregions of the PFC in rats, monkeys and humans.     

The effects of prefrontal lesions on working memory performance and theory

The effects of experimental lesions of the monkey prefrontal cortex have played a predominant role in current conceptualizations of the functional organization of the lateral prefrontal cortex, especially with regard to working memory. The loss or sparing of certain performance abilities has been shown to be attributable to differences in the specific requirements of behavioral testing (e.g., spatial vs. nonspatial memoranda) along with differences in the specific locations of applied ablations (e.g., dorsal vs. ventral prefrontal cortex). Such findings, which have accumulated now for over a century, have led to widespread acceptance that the dorsolateral and ventrolateral aspects of the prefrontal cortex may perform different, specialized roles in higher order cognition. Nonetheless, it remains unclear and controversial how the lateral prefrontal cortex is functionally organized. Two main views propose different types of functional specialization of the dorsal and ventral prefrontal cortex. The first contends that the lateral prefrontal cortex is segregated according to the processing of spatial and nonspatial domains of information. The second contends that domain specialization is not the key to the organization of the prefrontal cortex, but that instead, the dorsal and ventral prefrontal cortices perform qualitatively different operations. This report critically reviews all relevant monkey lesion studies that have served as the foundation for current theories regarding the functional organization of the prefrontal cortex. Our goals are to evaluate how well the existing lesion data support each theory and to enumerate caveats that must be considered when interpreting the relevant literature.     

Learning related modulation of functional retrieval networks in man

The medial temporal lobe has been implicated in studies of episodic memory tasks involving spatio-temporal context and object-location conjunctions. We have previously demonstrated that an increased level of practice in a free-recall task parallels a decrease in the functional activity of several brain regions, including the medial temporal lobe, the prefrontal, the anterior cingulate, the anterior insular, and the posterior parietal cortices, that in concert demonstrate a move from elaborate controlled processing towards a higher degree of automaticity. Here we report data from two experiments that extend these initial observations. We used a similar experimental approach but probed for effects of retrieval paradigms and stimulus material. In the first experiment we investigated practice related changes during recognition of object-location conjunctions and in the second during free-recall of pseudo-words. Learning in a neural network is a dynamic consequence of information processing and network plasticity. The present and previous PET results indicate that practice can induce a learning related functional restructuring of information processing. Different adaptive processes likely subserve the functional re-organisation observed. These may in part be related to different demands for attentional and working memory processing. It appears that the role(s) of the prefrontal cortex and the medial temporal lobe in memory retrieval are complex, perhaps reflecting several different interacting processes or cognitive components. We suggest that an integrative interactive perspective on the role of the prefrontal and medial temporal lobe is necessary for an understanding of the processing significance of these regions in learning and memory. It appears necessary to develop elaborated and explicit computational models for prefrontal and medial temporal functions in order to derive detailed empirical predictions, and in combination with an efficient use and development of functional neuroimaging approaches, to further the understanding of the processing significance of these regions in memory.     

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.     

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。     

Laminar cortical dynamics of cognitive and motor working memory, sequence learning and performance: toward a unified theory of how the cerebral cortex works

How does the brain carry out working memory storage, categorization, and voluntary performance of event sequences? The LIST PARSE neural model proposes an answer that unifies the explanation of cognitive, neurophysiological, and anatomical data. It quantitatively simulates human cognitive data about immediate serial recall and free recall, and monkey neurophysiological data from the prefrontal cortex obtained during sequential sensory-motor imitation and planned performance. The model clarifies why spatial and non-spatial working memories share the same type of circuit design. It proposes how laminar circuits of lateral prefrontal cortex carry out working memory storage of event sequences within layers 6 and 4, how these event sequences are unitized through learning into list chunks within layer 2/3, and how these stored sequences can be recalled at variable rates that are under volitional control by the basal ganglia. These laminar prefrontal circuits are variations of visual cortical circuits that explained data about how the brain sees. These examples from visual and prefrontal cortex illustrate how laminar neocortex can represent both spatial and temporal information, and open the way towards understanding how other behaviors derive from shared laminar neocortical designs.     

Autobiographical memory and the self in time: brain lesion effects, functional neuroanatomy, and lifespan development

Autobiographical remembering reflects an advanced state of consciousness that mediates awareness of the self as continuous across time. In naturalistic autobiographical memory, self-aware recollection of temporally and spatially specific episodes and generic factual information (both public and personal) operate in tandem. Evidence from both laboratory and real-life studies, however, suggests that these two processes can be dissociated. This paper reviews aging, lesion, and functional neuroimaging research on the anatomical substrates of autobiographical memory processes using a new measure, the Autobiographical Interview, and prospective collection of autobiographical material. Results indicate that autobiographical recollection is mediated by a distributed fronto-temporo-parietal system, with the anteromedial prefrontal cortex positioned to integrate sensory information with self-specific information. The emergence of autobiographical recollection at around age four coincides with the timing of prefrontal regressive cortical and progressive white matter changes that may support the development of this high-level capacity.     

Inactivation of the anterior cingulate cortex blocks expression of remote, but not recent, conditioned taste aversion memory

Previous studies have shown that medial prefrontal cortical regions, such as the anterior cingulate cortex (ACC), play a key role in the expression of remote spatial and contextual memory. To evaluate whether this role is conserved in hippocampal-independent tasks we trained mice in the conditioned taste aversion (CTA) paradigm. Lidocaine-induced inactivation of the ACC blocked the expression of CTA tested one month (remote), but not one day (recent), after conditioning with either a weak or strong unconditioned stimulus (US). These data suggest that the ACC may play a conserved role in remote memory, regardless of memory strength or content.     

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.     

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.