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Differential influences of negative emotion on spatial and verbal working memory: Evidence from event-related potential and source current density analysis.

We used the event-related potential technique to assess the influences of negative emotion on spatial and verbal working memory with a modified n-back task. In both spatial and verbal tasks, the anterior late positive component and the posterior P300 were affected by negative emotion. These effects were, however, greater in spatial tasks than in verbal ones. Especially, the parietal P300 was reduced by negative emotion in spatial tasks, but not in verbal tasks. Current density analysis revealed high current density in the frontal-parietal cortex, but only in the spatial tasks. The results suggest differential effects of negative emotion on spatial and verbal working memory and that the frontal-parietal cortex may be the area where negative emotion and spatial working memory interact.

Adult↗

Dissociable brain mechanisms for inhibitory control: effects of interference content and working memory capacity.

In this study, event-related fMRI was used to examine whether the resolution of interference arising from two different information contents activates the same or different neuronal circuitries. In addition, we examined the extent to which these inhibitory control mechanisms are modulated by individual differences in working memory capacity. Two groups of participants with high and low working memory capacity [high span (HS) and low span (LS) participants, respectively] performed two versions of an item recognition task with familiar letters and abstract objects as stimulus materials. Interference costs were examined by means of the recent negative probe technique with otherwise identical testing conditions across both tasks. While the behavioral interference costs were of similar magnitude in both tasks, the underlying brain activation pattern differed between tasks: The object task interference-effects (higher activation in interference trials than in control trials) were restricted to the anterior intraparietal sulcus (IPS). Interference effects for familiar letters were obtained in the anterior IPS, the left postero-ventral and the right dorsolateral prefrontal cortex (PFC) as well as the precuneus. As the letters were more discernible than the objects, the results suggest that the critical feature for PFC and precuneus involvement in interference resolution is the saliency of stimulus-response mappings. The interference effects in the letter task were modulated by working memory capacity: LS participants showed enhanced activation for interference trials only, whereas for HS participants, who showed better performance and also lower interference costs in the letter task, the above-mentioned neuronal circuitry was activated for interference and control trials, thereby attenuating the interference effects. The latter results support the view that HS individuals allocate more attentional resources for the maintenance of task goals in the face of interfering information from preceding trials with familiar stimulus materials.

Adult↗

Individual differences in amygdala activity predict response speed during working memory.

The human amygdala has classically been viewed as a brain structure primarily related to emotions and dissociated from higher cognition. We report here findings suggesting that the human amygdala also has a role in supporting working memory (WM), a canonical higher cognitive function. In a first functional magnetic resonance imaging (fMRI) study (n = 53), individual differences in amygdala activity predicted behavioral performance in a 3-back WM task. Specifically, higher event-related amygdala amplitude predicted faster response time (RT; r = -0.64), with no loss of accuracy. This relationship was not contingent on mood state, task content, or personality variables. In a second fMRI study (n = 21), we replicated the key finding (r = -0.47) and further showed that the correlation between the amygdala and faster RT was specific to a high working memory load condition (3-back) compared with a low working memory load condition (1-back). These results support models of amygdala function that can account for its involvement not only in emotion but also higher cognition.

Adolescent↗

Individual differences in working memory capacity predict visual attention allocation.

To the extent that individual differences in working memory capacity (WMC) reflect differences in attention (Baddeley, 1993; Engle, Kane, & Tuholski, 1999), differences in WMC should predict performance on visual attention tasks. Individuals who scored in the upper and lower quartiles on the OSPAN working memory test performed a modification of Egly and Homa's (1984) selective attention task. In this task, the participants identified a central letter and localized a displaced letter flashed somewhere on one of three concentric rings. When the displaced letter occurred closer to fixation than the cue implied, high-WMC, but not low-WMC, individuals showed a cost in the letter localization task. This suggests that low-WMC participants allocated attention as a spotlight, whereas those with high WMC showed flexible allocation.

Attention↗

A neural circuit basis for spatial working memory.

The maintenance of a mental image in memory over a time scale of seconds is mediated by the persistent discharges of neurons in a distributed brain network. The representation of the spatial location of a remembered visual stimulus has been studied most extensively and provides the best-understood model of how mnemonic information is encoded in the brain. Neural correlates of spatial working memory are manifested in multiple brain areas, including the prefrontal and parietal association cortices. Spatial working memory ability is severely compromised in schizophrenia, a condition that has been linked to prefrontal cortical malfunction. Recent computational modeling work, in interplay with physiological studies of behaving monkeys, has begun to identify microcircuit properties and neural dynamics that are sufficient to generate memory-related persistent activity in a recurrent network of excitatory and inhibitory neurons during spatial working memory. This review summarizes recent results and discusses issues of current debate. It is argued that understanding collective neural dynamics in a recurrent microcircuit provides a key step in bridging the gap between network memory function and its underlying cellular mechanisms. Progress in this direction will shed fundamental insights into the neural basis of spatial working memory impairment associated with mental disorders.

Animals↗

Binding across time: the selective gating of frontal and hippocampal systems modulating working memory and attentional states.

Temporal binding via 40-Hz synchronization of neuronal discharges in sensory cortices has been hypothesized to be a necessary condition for the rapid selection of perceptually relevant information for further processing in working memory. Binocular rivalry experiments have shown that late stage visual processing associated with the recognition of a stimulus object is highly correlated with discharge rates in inferotemporal cortex. The hippocampus is the primary recipient of inferotemporal outputs and is known to be the substrate for the consolidation of working memories to long-term, episodic memories. The prefrontal cortex, on the other hand, is widely thought to mediate working memory processes, per se. This article reviews accumulated evidence for the role of a subcortical matrix in linking frontal and hippocampal systems to select and "stream" conscious episodes across time (hundreds of milliseconds to several seconds). "Streaming" is hypothesized to be mediated by the selective gating of reentrant flows of information between these cortical systems and the subcortical matrix. The physiological mechanism proposed for this temporally extended form of binding is synchronous oscillations in the slower EEG spectrum (< 8 Hz).

Attention↗

Updating working memory for words: a PET activation study.

A PET study of 10 normal individuals was carried out to investigate the cerebral regions involved in the controlled updating of verbal working memory. Subjects viewed single concrete words on a computer monitor and detected occasional target words in an attended color. In the activating condition, a target was defined as a word that was identical to the previous word presented in the attended color. In the control condition, the target was a predesignated word. The same word lists, target probabilities, and target response demands were used for both conditions, with interword intervals constrained to ensure equivalence in the demand for target rehearsal. A comparison of the conditions found bilateral activation of dorsolateral prefrontal (middle frontal gyrus; MFG) and inferior parietal (supramarginal gyrus; SMG) cortical regions. Activation of the MFG is taken to reflect executive control by prefrontal regions over the working memory updating process linking posterior representations of the anticipated target stimulus to anterior representations of the planned response. It is proposed that the updating of the stimulus link is mediated via connections between the MFG and SMG. The role of the SMG as an amodal region binding the various modal representations in posterior association cortex of the word being retained in working memory is considered and reviewed. It is suggested that the combined activation of these regions is related to the executive control of goal-setting in planned behavior.

Blood Flow Velocity↗

Increased frontocerebellar activation in alcoholics during verbal working memory: an fMRI study.

Although there is clear evidence of alcoholism-related damage to the frontal lobes and cerebellum from neuroimaging, neuropathological, and neuropsychological studies, the functional role of the cerebellum and cerebrocerebellar circuits related to verbal working memory deficits of alcoholics have not been well studied. Alcoholic and nonalcoholic subjects performed a Sternberg verbal working memory task while receiving an fMRI scan in a 3T magnet. This task has been found in previous studies to reliably activate the articulatory control and phonological storage components of the phonological loop (left frontal, left temporal/parietal structures, right superior cerebellar regions) in young healthy controls. We hypothesized that the alcoholics would show a different pattern of activation from the controls, based on the regions of interest (ROIs) identified from a previous study of healthy subjects. Behavioral results showed the alcoholics to be performing at a comparable level to the matched controls in terms of accuracy and median reaction time, with no statistically significant differences. However, analysis of the functional data revealed that the alcoholics exhibited greater activation in the left frontal (BA44/45) and right superior cerebellum (HVI) regions relative to the matched controls. These findings suggest that brain activation in left frontal and right cerebellar regions that support the articulatory control system of verbal working memory may require a compensatory increase in alcoholics in order to maintain the same level of performance as controls.

Adult↗

Maintenance versus manipulation of information held in working memory: an event-related fMRI study.

One model of the functional organization of lateral prefrontal cortex (PFC) in primates posits that this region is organized in a dorsal/ventral fashion subserving spatial and object working memory, respectively. Alternatively, it has been proposed that a dorsal/ventral subdivision of lateral PFC instead reflects the type of processing performed upon information held in working memory. We tested this hypothesis using an event-related fMRI method that can discriminate among functional changes occurring during temporally separated behavioral subcomponents of a single trial. Subjects performed a delayed-response task with two types of trials in which they were required to: (1) retain a sequence of letters across the delay period (maintenance) or (2) reorder the sequence into alphabetical order across the delay period (manipulation). In each subject, activity during the delay period was found in both dorsolateral and ventrolateral PFC in both types of trials. However, dorsolateral PFC activity was greater in manipulation trials. These findings are consistent with the processing model of the functional organization of working memory in PFC.

Adult↗

Evidence for a dopaminergic link between working memory and agentic extraversion: an analysis of load-related changes in EEG alpha 1 activity.

Several lines of research point to the possibility of a partially overlapping dopaminergic foundation of the trait of agentic extraversion and individual differences in working memory functioning. This study investigates interactive effects of agentic extraversion and dopamine on spectral EEG measures of working memory. Using EEG activity in the alpha 1 band (8-10.25 Hz) as a dependent variable, we tested in a randomized double-blind design the effects of the D2-dopamine antagonist sulpiride during the performance of four load-graded n-back working memory tasks in participants high versus low in agentic extraversion. We expected extraversion-related differences in the load-responsivity pattern to be reversed by sulpiride, and the alpha 1 anterior-posterior difference actually depicted this reversal effect. However, in contrast to our expectations this effect was largely due to parietal instead of frontal sites.

Adolescent↗

Division of labor among distinct subtypes of inhibitory neurons in a cortical microcircuit of working memory.

A conspicuous feature of cortical organization is the wide diversity of inhibitory interneurons; their differential computational functions remain unclear. Here we propose a local cortical circuit in which three major subtypes of interneurons play distinct roles. In a model designed for spatial working memory, stimulus tuning of persistent activity arises from the concerted action of widespread inhibition mediated by perisoma-targeting (parvalbumin-containing) interneurons and localized disinhibition of pyramidal cells via interneuron-targeting (calretinin-containing) interneurons. Moreover, resistance against distracting stimuli (a fundamental property of working memory) is dynamically controlled by dendrite-targeting (calbindin-containing) interneurons. The experimental observation of inverted tuning curves of monkey prefrontal neurons recorded during working memory supports a key model prediction. This work suggests a framework for understanding the division of labor and cooperation among different inhibitory cell types in a recurrent cortical circuit.

Animals↗

DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability.

The C957T polymorphism in the dopamine D2 receptor (DRD2) gene and the Val158Met polymorphism in the Catechol-O-Methyl-Transferase (COMT) gene affect dopamine transmission and have been found to be associated with schizophrenia. Since DRD2 in mice and the COMT gene in humans modulate working memory, we examined the relationship and possible interaction of both polymorphisms to working memory performance in 188 healthy adults. Subjects having the DRD2 C/C allele showed the poorest performance in a word serial position test. Moreover, the effect of the C957T genotype was strengthened when interaction with the COMT Val158Met polymorphism was included in the analysis. We propose that an interaction of the DRD2 C957T and COMT Val158Met may be involved in the generation of some working memory deficits in schizophrenia.

Adolescent↗

Working memory deficits in multiple sclerosis: a controlled study with auditory P600 correlates.

BACKGROUND: Recently, the P600 component of event related potentials, a waveform that is conceived to be generated and/or modulated by basal ganglia and cingulate area has been considered an index of the completion of any synchronised operation after target detection, having much in common with working memory operation. Moreover, dysfunction of these brain structures as well as working memory deficits have been implicated in the pathophysiology of multiple sclerosis. The aim of this study was to investigate the patterns of P600 elicited during a working memory test in multiple sclerosis patients compared with healthy controls. METHODS: Twenty two definite, chronic progressive multiple sclerosis patients, with recent exacerbation of their illness, and 20 normal subjects matched for age, sex, and educational level, were studied with a computerised version of the digit span test of Wechsler batteries. Auditory P600 were measured during the anticipatory period of this test. RESULTS: The patient group, as compared with healthy controls, showed significantly reduced latencies of P600 at left frontal areas and reduced P600 amplitudes at left temporoparietal region. Moreover, memory performance of patients was significantly more impaired when compared with healthy controls. CONCLUSIONS: These findings may indicate that multiple sclerosis is associated with abnormal features of the completion of synchronised operation after target detection, as they are reflected by P600 amplitudes and latencies. Dysfunction of this mechanism may contribute to the identification of basic cognitive processes that could account for the cognitive deficits in multiple sclerosis.

Adult↗

Frontal lobe function in Korsakoff and non-Korsakoff alcoholics: planning and spatial working memory.

Groups of Korsakoff (KS) and non-Korsakoff alcoholics (ALC) and a group of normal volunteers, matched for age and verbal IQ, were tested on traditional neuropsychological tests of frontal lobe function and on computerized tests of planning (the Tower of London task) and spatial working memory. KS demonstrated deficits on the planning task which could not be explained by abnormalities of memory, including spatial span, or by visuoperceptive disturbances. KS were also impaired on the spatial working memory task, in part because of the failure to adopt an organized strategy. ALC exhibited fewer impairments which could not be attributed to deficits in either planning or spatial working memory. On Nelson's modified Wisconsin Card Sorting Task, KS and ALC achieved fewer categories than controls but only KS made perseverative errors. The data suggest that in the alcoholic Korsakoff's syndrome there is a specific disturbance of frontal-lobe function in addition to amnesia. The impairment seen in chronic alcoholics without Korsakoff's syndrome, on the other hand, do not reflect specific frontal dysfunction.

Adult↗

Aging and repetition priming for targets and distracters in a working memory task.

A combined working memory/repetition priming task was administered to 13 young (mean age 23) and 13 elderly (mean age 69) adults. Each participant memorized a sample target face at the beginning of a trial and then determined whether each of 13 serially presented test faces matched the sample target. In each trial, both the target and one particular distracter face were repeated during the test phase. Within-trial repetition priming effects indicated the contribution of implicit memory to task performance. Response times decreased as items were tested repeatedly within a trial, but this decrement was greater for distracters than for targets. Young and older participants were equally accurate at identifying targets, but elderly were slightly less accurate for distracters. Elderly participants showed repetition priming effects for both targets and distracters, while the young showed such effects only for distracters. The results suggest that active maintenance in working memory, but not inhibition or rejection of distracters, may suppress implicit memory systems.

Adolescent↗

The episodic buffer: a new component of working memory?

In 1974, Baddeley and Hitch proposed a three-component model of working memory. Over the years, this has been successful in giving an integrated account not only of data from normal adults, but also neuropsychological, developmental and neuroimaging data. There are, however, a number of phenomena that are not readily captured by the original model. These are outlined here and a fourth component to the model, the episodic buffer, is proposed. It comprises a limited capacity system that provides temporary storage of information held in a multimodal code, which is capable of binding information from the subsidiary systems, and from long-term memory, into a unitary episodic representation. Conscious awareness is assumed to be the principal mode of retrieval from the buffer. The revised model differs from the old principally in focussing attention on the processes of integrating information, rather than on the isolation of the subsystems. In doing so, it provides a better basis for tackling the more complex aspects of executive control in working memory.

Journal Article↗

Patterns of content, contextual, and working memory impairments in schizophrenia and nonamnesic alcoholism.

This study used tests of content memory (item recognition of words and abstract designs), context memory (order recognition of verbal and nonverbal items), and working memory (recognition at a short retention interval) to examine patterns of performance in 27 schizophrenic patients, 52 chronic alcoholic patients, and 66 healthy control participants. When performance was age- and IQ-adjusted the schizophrenia group was significantly impaired in item and order recognition of verbal and nonverbal material; the alcoholic group was impaired only in order recognition for both material types. Item- and order-recognition deficits in the schizophrenia group were greatest at the shortest retention intervals, a pattern previously observed in patients with Parkinson's disease, suggesting a prominence of a working memory deficit in schizophrenia.

Adult↗

Gating of human theta oscillations by a working memory task.

Electrode grids on the cortical surface of epileptic patients provide a unique opportunity to observe brain activity with high temporal-spatial resolution and high signal-to-noise ratio during a cognitive task. Previous work showed that large-amplitude theta frequency oscillations occurred intermittently during a maze navigation task, but it was unclear whether theta related to the spatial or working memory components of the task. To determine whether theta occurs during a nonspatial task, we made recordings while subjects performed the Sternberg working memory task. Our results show event-related theta and reveal a new phenomenon, the cognitive "gating" of a brain oscillation: at many cortical sites, the amplitude of theta oscillations increased dramatically at the start of the trial, continued through all phases of the trial, including the delay period, and decreased sharply at the end. Gating could be seen in individual trials and varying the duration of the trial systematically varied the period of gating. These results suggest that theta oscillations could have an important role in organizing multi-item working memory.

Adolescent↗