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PubMed1991

N-methyl-D-aspartate antagonists and working memory performance: comparison with the effects of scopolamine, propranolol, diazepam, and phenylisopropyladenosine.

The effects of the competitive N-methyl-D-aspartate (NMDA) antagonists CPP (5 & 10 mg/kg) and NPC 12626 (25 & 40 mg/kg) and the noncompetitive NMDA antagonists phencyclidine (1, 3, & 6.25 mg/kg) and MK 801 (0.1 & 0.2 mg/kg) on performance of rats on a nonspatial delayed matching-to-sample working memory task were evaluated. At the highest dose, each NMDA antagonist reduced choice accuracy at all retention intervals. In contrast, the reference anticholinergic agent scopolamine selectively reduced accuracy at long retention intervals, suggesting that scopolamine but not the NMDA antagonists directly interfered with time-dependent working memory retention. Propranolol, diazepam, and phenylisopropyladenosine had little or no effect on choice accuracy, suggesting that noradrenergic, gamma-aminobutyric acid-diazepam, and adenosine receptors may be relatively unimportant for working memory performance as assessed in this task. The NMDA antagonists also differed from scopolamine in that doses of NMDA antagonists that reduced response accuracy also reduced response probability, altered bias (competitive antagonists only), and increased intertrial interval responding (noncompetitive antagonists only). It was concluded that NMDA antagonists disrupt cognitive functions including, but not limited to, those required for accurate working memory performance.

Amino Acids↗

PubMed1996

Working memory, attention, and communication disturbances in schizophrenia.

The authors hypothesized that schizophrenic communication disturbances reflect specific cognitive deficits in the areas of working memory and attention. They examined the cognitive correlates of communication disturbances, as measured by linguistic reference performance, in schizophrenic (n = 48), bipolar (n = 24), and nonpsychiatric control (n = 23) individuals. Reference performance ratings in the schizophrenic patients were associated with scores on tests of working memory and attention and were not related to performance on concept formation or verbal fluency tests. In contrast, in the bipolar and nonpsychiatric individuals, reference performance was associated with concept formation and verbal fluency test scores but was not related to performance on tests of working memory. Implications with respect to the processes underlying schizophrenic communication disturbances are discussed.

Adult↗

PubMed2000

Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain.

The indirect catecholamine agonist methylphenidate (Ritalin) is the drug treatment of choice in attention deficit/hyperactivity disorder (AD/HD), one of the most common behavioral disorders of childhood (DSM-IV), although symptoms may persist into adulthood. Methylphenidate can enhance cognitive performance in adults and children diagnosed with AD/HD (Kempton et al., 1999; Riordan et al., 1999) and also in normal human volunteers on tasks sensitive to frontal lobe damage, including aspects of spatial working memory (SWM) performance (Elliott et al., 1997). The present study investigated changes in regional cerebral blood flow (rCBF) induced by methylphenidate during performance of a self-ordered SWM task to define the neuroanatomical loci of the beneficial effect of the drug. The results show that the methylphenidate-induced improvements in working memory performance occur with task-related reductions in rCBF in the dorsolateral prefrontal cortex and posterior parietal cortex. The beneficial effects of methylphenidate on working memory were greatest in the subjects with lower baseline working memory capacity. This is to our knowledge the first demonstration of a localization of a drug-induced improvement in SWM performance in humans and has relevance for understanding the treatment of AD/HD.

Adrenergic Uptake Inhibitors↗

PubMedDate not supplied

Contribution of working memory to transient activation in human inferior prefrontal cortex during performance of the Wisconsin Card Sorting Test.

The Wisconsin Card Sorting Test (WCST) is the standard task paradigm to detect human frontal lobe dysfunction. In this test, subjects sort card stimuli with respect to one of three possible dimensions (color, form and number). These dimensions are changed intermittently, whereupon subjects are required to identify by trial and error a new correct dimension and flexibly shift cognitive set. We decomposed the cognitive requirements at the time of the dimensional changes of the WCST, using functional magnetic resonance imaging (fMRI). By explicitly informing subjects of a new correct dimension, the working memory load for the trial-and-error identification of the new dimension was removed. Event-related fMRI still revealed transient activation time-locked to the dimensional changes in areas in the posterior part of the inferior frontal sulci. However, the activation was significantly smaller than in the original WCST in which subjects had to use working memory to identify the new dimension by trial and error. Furthermore, these areas were found to spatially overlap the areas activated by a working memory task. These results suggest that working memory and set-shifting act cooperatively in the same areas of prefrontal cortex to adapt us to changing environments.

Adult↗

PubMed1993

Chronic nicotine reverses working memory deficits caused by lesions of the fimbria or medial basalocortical projection.

Nicotine has been found in a variety of studies to improve performance in memory tasks. This study was conducted to determine if chronic nicotine administration is useful in counteracting the working memory deficits seen after lesions of the fimbria or the medial basalocortical projection. Rats were trained to asymptotic performance on a working memory version of the radial-arm maze. Then, they were given knife cut lesions of the fimbria or the medial basalocortical projection or underwent sham surgeries. At the time of surgery, rats in each treatment group were implanted with either nicotine-containing or placebo glass and Silastic pellets. Rats with fimbria or basalocortical lesions showed a significant decline in working memory performance. Chronic nicotine significantly improved choice accuracy in both lesioned and unlesioned rats. Nicotine treatment restored performance of the lesioned rats to control levels. These data show that in addition to improving memory performance in normal rats, nicotine can counteract lesion-induced memory impairments. Nicotine also may be useful for treatment of disease-related memory impairments such as seen in Alzheimer's disease.

Animals↗

PubMed2006

Specific changes in hippocampal spatial codes predict spatial working memory performance.

This study examined the relationship between hippocampal place fields and spatial working memory. Place cells were recorded while rats solved a spatial working memory task in light and dark testing conditions. Rats made significantly more errors when tested in darkness, and although place fields changed in multiple ways in darkness, only changes in place field specificity predicted the degree of impaired spatial memory. This finding suggests that more spatially distinct place fields may contribute to hippocampal-dependent mnemonic functions.

Animals↗

PubMed1998

Nonverbal working memory of humans and monkeys: rehearsal in the sketchpad?

Investigations of working memory tend to focus on the retention of verbal information. The present experiments were designed to characterize the active maintenance rehearsal process used in the retention of visuospatial information. Rhesus monkeys (Macaca mulatta; N = 6) were tested as well as humans (total N = 90) because these nonhuman primates have excellent visual working memory but, unlike humans, cannot verbally recode the stimuli to employ verbal rehearsal mechanisms. A series of experiments was conducted using a distractor-task paradigm, a directed forgetting procedure, and a dual-task paradigm. No evidence was found for an active maintenance process for either species. Rather, it appears that information is maintained in the visuospatial sketchpad without active rehearsal.

Adolescent↗

PubMed2003

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.

Journal Article↗

PubMed2005

Heritability of selective attention and working memory in preschoolers.

In this study aspects of selective attention and working memory were tested in a large sample of nearly 6-year old monozygotic and dizygotic twin pairs, using a computerized test battery (Amsterdam Neuropsychological tasks). In the selective attention task the presence of a foil signal (target signal at an irrelevant location) resulted in more false alarms than a non-target signal. In the working memory task an increase in memory load lead to an increase in response times and errors. We analyzed variations in absolute performance parameters (overall speed and accuracy) and relative performance parameters (increase in errors and/or reaction time). The results showed clear familial resemblances on performance. It proved difficult to ascribe these effects to shared genes or to shared environment. An exception was memory search rate, which was clearly heritable.

Attention↗

PubMed2005

Revisiting the role of Broca's area in sentence processing: syntactic integration versus syntactic working memory.

Most previous neuroimaging studies of sentence processing have associated Broca's area with syntactic processing; however, the exact nature of the processes subserved by this brain region is yet not well understood. Although some authors suggest that Brodmann area (BA) 44 of the left inferior frontal gyrus (i.e., Broca's area) is relevant for syntactic integration processes, others claim that it is associated with working memory mechanisms relevant for language processing. To dissociate these two possible functions, the present study investigated hemodynamic responses elicited while participants processed German indirect wh-questions. Activation increases were observed in left BA 44 together with superior temporal areas and right hemispheric homologues for sentences with noncanonical word order, in which a verb argument was dislocated from its canonical position over a relatively long distance. In these sentences, syntactic working memory load was assumed to be greatest. In contrast, no activation increase was elicited by object-initial as opposed to subject-initial sentences that did not differ with respect to working memory costs but with respect to syntactic integration costs. These data strongly suggest that Broca's area plays a critical role in syntactic working memory during online sentence comprehension.

Adult↗

PubMed2004

Modular biased-competition and cooperation: a candidate mechanism for selective working memory.

Prefrontal cortex (PFC) has been suggested to play an important role in executive cognitive functions, participating in planning and controlling behaviour. The results of several recent electrophysiological studies indicate that PFC might be involved not only in the active maintenance of information but in doing so in a context- or task-dependent manner. In a delayed-match-to-sample paradigm, recordings from neurons in the PFC showed their ability to selectively represent information, which is needed for task completion, suggesting that task-irrelevant information does not access working memory. We present a neurodynamical computational model of a part of the PFC to account for the selective representation of information in working memory. We show that a network of biological realistic integrate-and-fire excitatory and inhibitory neurons, implementing the mechanisms of local or modular biased-competition, which is transmitted through cooperation to different subsets of neuronal pools, can explain the formation of selective context-dependent working memory. The modes of operation of the network are characterized and the corresponding parameter settings revealed. Modular competition and cooperation might constitute general mechanisms for implementing context-dependent formation of working memory.

Action Potentials↗

PubMed2002

Functional heterogeneity within Broca's area during verbal working memory.

In previous fMRI research, we found that two subregions of the left inferior frontal cortex showed distinct patterns of activity during a verbal working memory task. Specifically, a more dorsal region tracked with performance, while a more ventral region was sensitive to lexical status. To test the veracity of this finding, we developed a new method for meta-analysis of neuroimaging results. In this method, Gaussian probability distributions are formed around stereotaxic coordinates obtained from published neuroimaging studies. These probability distributions are then combined to identify regions of convergence across studies. When this method was applied to prior studies of working memory, the results largely paralleled those from earlier reviews of the literature on working memory, but also confirmed our empirical findings showing distinct foci within Broca's area. Further application of this meta-analytic technique substantiated the dissociation in these regions for performance and sublexical processing. These results help to validate a novel approach for meta-analysis of neuroimaging findings that avoids many of the subjective assumptions involved in alternative approaches.

Diagnostic Imaging↗

PubMedDate not supplied

Working memory for temporal and nontemporal events in monkeys.

This is the first report that introduces appropriate behavioral tasks for monkeys for investigations of working memory for temporal and nontemporal events. Using several behavioral tests, the study also shows how temporal information is coded during retention intervals in the tasks. Each of three monkeys was trained with two working memory tasks: delayed matching-to-sample of stimulus duration (DMS-D) and delayed matching-to-sample of stimulus color (DMS-C). The two tasks employed an identical apparatus and responses and differed only in the temporal and nontemporal attribute of the stimuli to be retained for correct performance. When a retention interval between the sample and comparison stimuli was prolonged, the monkeys made more incorrect responses to short samples in the DMS-C task, suggesting "trace decay" of memory for short stimuli. However, the same monkeys showed no such increase in incorrect responses to short samples in the DMS-D task, suggesting active coding of temporal information, that is, the length of stimulus duration, during the retention interval. When variable lengths of samples were presented with a fixed retention interval, the monkeys made more incorrect responses when length differences between short and long samples were small in the DMS-D task, but not in the DMS-C task. This suggests that the codes of working memory retained in the DMS-D task were not absolute (analogical) but rather were relative (categorical) and related to differences in the duration of the samples.

Animals↗

PubMed2003

Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study.

BACKGROUND: This study examined cerebral function in posttraumatic stress disorder (PTSD) during the updating of working memory to trauma-neutral, verbal information. METHODS: Ten PTSD and matched control subjects completed a visuoverbal target detection task involving continuous updating (Variable target condition) or no updating (Fixed target condition) of target identity, with updating activity estimated by condition comparison. RESULTS: Normal updating activity using this paradigm involved bilateral activation of the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobe. The PTSD group lacked this activation in the left hemisphere and was significantly different from control subjects in this regard, but showed additional activation in the superior parietal lobe, bilaterally. CONCLUSIONS: The pattern of parietal activation suggests a dependence on visuospatial coding for working memory representation of trauma-neutral, verbal information. Group differences in the relative involvement of the DLPFC indicate less dependence in PTSD on the executive role normally attributed to the left DLPFC for monitoring and manipulation of working memory content in posterior regions of the brain.

Female↗

PubMed2006

The role of the dorsal CA3 hippocampal subregion in spatial working memory and pattern separation.

A delayed-match-to-sample for spatial location task was used to measure spatial pattern separation and working memory. On each trial, an object covered a baited food well in one of 15 spatial locations along a row of food wells perpendicular to the start box. Once the rat exited the start box, displaced the object to receive a food reward and then returned to the startbox, the same food well was then quickly re-baited, an identical object was positioned to cover the food well and another identical object was positioned in a different location along the row of food wells covering a different unbaited food well. On the ensuing choice phase, the animal was allowed to choose between the two objects. The object that covered the same food well as the object in the sample phase was the correct choice and the second foil object was the incorrect choice. Five spatial separations (15-105 cm) were randomly used to separate the correct object from the foil object during the choice phase. Once a preoperative criterion was met, each rat received bilateral intracranial infusions of either ibotenic acid or the vehicle into the CA3 subregion of the dorsal hippocampus. Following surgery, rats with CA3 lesions were significantly impaired relative to controls across all spatial separations suggesting that CA3 lesions impaired working memory. Although the dorsal CA3 subregion of the hippocampus may play a role in pattern separation, the data suggest that this region is critically involved in spatial working memory.

Animals↗

PubMed2004

Striatal contributions to working memory: a functional magnetic resonance imaging study in humans.

Although the role of the frontal cortex in executive performance has been widely accepted, issues regarding the contribution of subcortical structures to these functions remain unresolved. In this study, the neural circuitry underlying selective subcomponents of working memory was investigated using event-related functional magnetic resonance imaging (fMRI). Ten healthy volunteers performed a verbal memory task, which allowed different aspects of working memory function such as maintenance, retrieval and manipulation to be tested within the same general paradigm. During performance of this task as a whole, fMRI revealed increases in signal intensity throughout the frontostriatal network. However, when signal intensity during the manipulation of information within working memory was compared to that during periods requiring only simple maintenance and retrieval, significant changes were observed only in the caudate nuclei, bilaterally. These results suggest an essential and specific role for the caudate nucleus in executive function, which may underlie the cognitive disturbances observed in frontostriatal neurodegenerative disorders such as Parkinson's disease.

Aged↗

PubMed2001

Neuroanatomical discrimination between manipulating and maintaining processes involved in verbal working memory; a functional MRI study.

We used functional magnetic resonance imaging (fMRI) to investigate neural correlates of processes concerning store and manipulation in verbal working memory. We prepared a revised lag 1 digit span, digit span and a simple number detection task. Specific activities in association with manipulating process were identified in the right middle (BA 9/46) and left precentral gyrus (BA 6). Activated areas specific to maintaining process were detected in the right middle (right BA 11/10) and medial (BA 6) frontal gyri, the right inferior parietal lobule (BA 40), and the left middle (BA 9) and inferior frontal gyri (BA 44). The process-nonspecific activated areas common to two processes were identified in the right inferior frontal gyrus (BA 47) and the left superior parietal lobule (BA 7). Using the signal percent change of each subject, we calculated the correlation coefficients among each activated area. The results of this analysis showed that two processes of verbal working memory were clearly discriminated. The two essential processes of manipulation and maintenance in working memory seem to activate process-specific and overlapping (process-nonspecific) areas, but the patterns of combination were definitely different.

Adult↗

PubMed2001

The role of rat dorsomedial prefrontal cortex in working memory for egocentric responses.

The present experiment studied the effects of quinolinic acid (90 mM) lesions of the medial precentral and anterior cingulate on working memory for egocentric responses. Rats were trained on a delayed match-to-sample task that involved memory for a 90 degrees right or left turn. The results indicated that lesioned rats had significantly decreased scores during the 10 s delay condition compared to presurgery levels. An increase in the delay to 20 s significantly reduced working memory performance in the lesioned rats compared to that of controls. These findings suggest that the rat medial precentral and/or anterior cingulate area play an important role in working memory for egocentric responses.

Animals↗