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Effects of tryptophan loading on verbal, spatial and affective working memory functions in healthy adults.

Serotonin (5-HT) appears to modulate affective behaviours by providing a homeostatic threshold around which other transmitters respond. This general principle of activity should hold for other types of behaviour, including cognition, but has not been extensively examined. We hypothesized, based on past findings, that increased 5-HT would constrain prefrontally guided working memory functions that are mediated by catecholamine neurotransmitters. Healthy adults ingested amino acid compounds designed to deplete and load systemic tryptophan levels in a repeated-measures crossover design. Outcome variables included total plasma tryptophan, serum prolactin levels and self-report measures of mood, as well as measures of motor skill, attention, memory span and working memory for verbal, spatial and affective stimuli. Our findings indicate decrements in working memory for verbal and affective stimuli following tryptophan loading versus depletion, as well as subtle changes in vigilant attention and motor coordination. Implications for the aetiology and treatment of affective disorders and psychosis are discussed.

Adolescent↗

Working memory impairment in early multiple sclerosis. Evidence from an event-related potential study of patients with clinically isolated myelopathy.

Auditory and visual event-related potentials were recorded during a short-term memory task in 24 patients who had recently presented with symptomatically and clinically isolated spinal cord syndromes suspected to be due to multiple sclerosis, and in 24 matched control subjects. Event-related potentials (ERPs) were recorded during two sequential components of the working memory task, first the temporary active memorizing of sets of digits and secondly, their subsequent manipulation, namely digit-probe recognition and matching. The patients' reaction times were slower and showed larger increments than those of the control subjects as the number of items to be memorized was increased. The patients' ERPs during both memorizing and probe matching/recognition phases differed significantly from control subjects for both auditory and visual presentations. The more marked changes were seen in a subgroup of eight patients who had the lowest levels of performance on a battery of general tests of memory and who also made significantly more errors in the working memory task as the memory load increased. In this subgroup, the abnormalities of the ERPs during recognition and matching tests occurred in the component of the response that has been shown to be sensitive to memory loading in healthy control subjects. This study provides objective evidence of subclinical working memory dysfunction in patients at an early stage of demyelinating disease, i.e. when they first present with clinically isolated spinal cord lesions and before they have developed symptoms of cognitive or memory dysfunction. The defect at this early stage is either restricted to processes involved in the formation of a memory trace or, more probably, involves both trace formation and the mechanisms that underly recognition ('retrieval') and matching of memory traces in working memory.

Adult↗

Dynamic synchrony of firing in the monkey prefrontal cortex during working-memory tasks.

Synchronized firing among neurons in the working brain is inferred to reflect coding by cell assemblies, which dynamically change their sizes and functional connections to encode various information. It therefore follows that, if synchronized firing reflects cell-assembly coding, it should show dynamic changes that depend on the tasks and events being processed and on the distance between the neurons. By using unique spike-sorting and multi-neuronal recording methods, we investigated such dynamics of synchrony in the prefrontal cortex of monkeys while they were successively performing two tasks in which working memory for either stimulus duration or color was required. Forty-eight percent of 1405 neuronal pairs showed firing synchrony during the performance of the tasks. Almost half of such neuronal pairs showed fixed synchrony and constantly fired together in both tasks. However, some neuronal pairs showed task-dependent synchrony that appeared in only one of the tasks. Moreover, the other neuronal pairs showed event-task-dependent synchrony that appeared during stimulus or retention periods in the tasks, but the periods showing synchrony varied between the tasks. Fixed synchrony and task-dependent synchrony were mostly observed among neighboring neurons and showed little variation of spike timings; the event-task-dependent synchrony, in contrast, was more often detected among distant neurons with larger variation of spike timings than the other two types of synchrony. These results suggest that some closely neighboring neurons have dynamic and sharp synchrony to represent certain situations (tasks), whereas some distant neurons show more dynamic and unstable synchronous firing to represent quickly changing events being processed in working memory.

Action Potentials↗

Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease.

OBJECTIVES: Cognitive impairment is a common feature in Parkinson's disease (PD) and is an important predictor of quality of life. Past studies showed that some aspects of cognition, such as working memory, can be enhanced following dopaminergic therapy and transcranial magnetic stimulation. The aim of our study was to investigate whether another form of noninvasive brain stimulation, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability, is associated with a change in a working memory task performance in PD patients. METHODS: We studied 18 patients (12 men and 6 women) with idiopathic PD. The patients performed a three-back working memory task during active anodal tDCS of the left dorsolateral prefrontal cortex (LDLPFC), anodal tDCS of the primary motor cortex (M1) or sham tDCS. In addition, patients underwent two different types of stimulation with different intensities: 1 and 2 mA. RESULTS: The results of this study show a significant improvement in working memory as indexed by task accuracy, after active anodal tDCS of the LDLPFC with 2 mA. The other conditions of stimulation: sham tDCS, anodal tDCS of LDLPFC with 1 mA or anodal tDCS of M1 did not result in a significant task performance change. CONCLUSION: tDCS may exert a beneficial effect on working memory in PD patients that depends on the intensity and site of stimulation. This effect might be explained by the local increase in the excitability of the dorsolateral prefrontal cortex.

Aged↗

The presence of working memory without explicit recall in a critically ill patient.

UNLABELLED: We describe an intubated patient sedated with propofol who interacted with caregivers, demonstrating intact "working memory." When neuromuscular blockade and bispectral index (BIS) monitoring were instituted, a greatly reduced amount of sedative achieved BIS values less than 60. Neither the sedation that allowed working memory nor the lighter sedation that produced BIS values less than 60 resulted in recall. This experience suggests that working memory demonstrated when BIS values are less than 60 is unlikely to lead to recall. IMPLICATIONS: The presence of intact working memory during sedation is a poor predictor of explicit recall when bispectral index values are maintained less than 60.

Adolescent↗

The hippocampus, time and working memory.

Rats were trained on a discrete trial working memory leverpress alternation task, following hippocampal lesions (HC), cortical control lesions (CC) or sham operations (SO). Each trial consisted of a forced information response, for which a randomly selected lever was presented followed by a free choice stage, when both levers were presented. The rats were rewarded for pressing the lever which had not been presented at the information stage. When the information response was not rewarded, all rats learnt the task equally well at IRIs of up to 12.75 sec. When the information response was rewarded, the HC rats showed impaired choice accuracy. The extent of this impairment depended on the IRI, being greatest at long IRIs, and least at short ones. Varying the number of leverpresses required to complete the information response affected choice accuracy equivalently in all groups: all rats chose significantly less accurately when only one leverpress was required than when ten leverpresses were required. There was no interaction between the lesion treatments and the information response requirements. It was concluded that both the length of the IRI and the occurrence of events during the IRI determine the extent of the hippocampal lesion-induced performance deficit in working memory tasks. It is proposed that hippocampal damage disrupts an intermediate-term, high-capacity memory buffer, but leaves both a residual short-term memory system and the long-term retention of associations unaffected. This proposal leads to the prediction that reference memory tasks should also be affected by hippocampal lesions when a delay is introduced between making a response and being rewarded for doing so.

Animals↗

The impact of specific language impairment on working memory in children with ADHD combined subtype.

The objective of this study was to examine the impact of comorbid specific language impairment (SLI) on verbal and spatial working memory in children with DSM-IV combined subtype Attention Deficit Hyperactivity Disorder (ADHD-C). Participants were a clinical sample of 812- to 1212-year-old children diagnosed with ADHD-C. A group of ADHD-C with SLI was compared to a group of ADHD-C without SLI, and a group of normal children, matched on age and nonverbal intelligence. The results show that ADHD-C children with SLI scored significantly lower than those without SLI and normal children, on verbal working memory measures only. Both ADHD groups performed normally on spatial working memory measures. It is concluded that working memory deficits are not a specific characteristic of ADHD but are associated with language impairments. The importance of screening for language disorders in studies of neuropsychological functioning in children with ADHD is emphasized.

Adolescent↗

A complexity theory model in science education problem solving: random walks for working memory and mental capacity.

The present study examines the role of limited human channel capacity from a science education perspective. A model of science problem solving has been previously validated by applying concepts and tools of complexity theory (the working memory, random walk method). The method correlated the subjects' rank-order achievement scores in organic-synthesis chemistry problems with the subjects' working memory capacity. In this work, we apply the same nonlinear approach to a different data set, taken from chemical-equilibrium problem solving. In contrast to the organic-synthesis problems, these problems are algorithmic, require numerical calculations, and have a complex logical structure. As a result, these problems cause deviations from the model, and affect the pattern observed with the nonlinear method. In addition to Baddeley's working memory capacity, the Pascual-Leone's mental (M-) capacity is examined by the same random-walk method. As the complexity of the problem increases, the fractal dimension of the working memory random walk demonstrates a sudden drop, while the fractal dimension of the M-capacity random walk decreases in a linear fashion. A review of the basic features of the two capacities and their relation is included. The method and findings have consequences for problem solving not only in chemistry and science education, but also in other disciplines.

Adolescent↗

Effects of ethanol on working memory and attention in pigeons.

To determine whether the effects of ethanol on working memory are mediated by a secondary effect on attention, dose-response curves for ethanol were determined in eight pigeons trained under a titrating matching-to-sample (TMTS) procedure, in eight pigeons trained under a discrete-trial measure of attention, and in eight pigeons trained under a continuous-trial measure of attention. Ethanol decreased accuracy under the TMTS procedure following the three highest doses (1, 1.8, and 3 g/kg). Only the highest dose (3 mg/kg) decreased rates of responding. Attention, as measured under the discrete-trial procedure, was affected only by the two highest doses (1.8 and 3 g/kg). The 3-g/kg dose caused significant decreases in the probability of a hit and probability of a correct rejection, as well as significant increases in the probability of an error of omission and response latencies. Sensitivity to the signal decreased following 1.8 and 3 g/kg ethanol. Under the continuous-trial procedure, ethanol caused a peak in false alarms after the 1.8-g/kg dose, decreased the probability of a hit following the 1.8- and 3-g/kg doses, and increased probability of a miss at all doses. Sensitivity to the signal was not affected. A comparison of the dose-response curves for the TMTS procedure and the two measures of attention revealed that working memory (TMTS) was decreased by a lower dose than that affecting attention. This suggests that the effects of ethanol on working memory are not mediated by the subject's ability to pay attention to stimulus changes in the environment.

Algorithms↗

Working memory involvement in emotion-based processes underlying choosing advantageously.

The Iowa Gambling Task (IGT) is widely used to assess decision making under conditions of uncertainty in clinical as well as in nonclinical populations. However, there is still debate as to whether normal performance at this task relies on implicit, emotion-based processes that are independent of working memory. To clarify the role of working memory on normal performance on the IGT, participants performed the task under low or high working memory load. We used a modified version of the original task, in which the position of the four decks was randomized between trials. Results showed that only participants performing under low memory load significantly chose more advantageously halfway through the task. In addition, when comparing the number of cards chosen from the two decks with frequent losses, one advantageous and one disadvantageous, only participants performing under low memory load chose more cards from the advantageous deck. The present findings indicate that the processes underlying optimal advantageous performance on the IGT rely on working memory functions.

Adult↗

Working memory impairments in alcohol-dependent participants without clinical amnesia.

BACKGROUND: The delayed alternation (DA) task is highly sensitive to the deficits of nonhuman animals with alcohol-related brain damage. DA is thought to measure working memory which serves as a temporary store for processing of information. However, performance on this type of task has only been investigated in alcohol-dependent humans with severe cognitive deficits. The aim of the current study was to explore the validity of DA as a test sensitive to alcohol-related brain damage by manipulating storage and processing components in three versions of the task. It was hypothesized that alcohol-dependent people would perform worse than control participants and that their deficits would be more pronounced in DA versions with maximal working memory demands. METHODS: A sample of 12 alcohol-dependent participants without Wernicke-Korsakoff syndrome was compared with a sample of 12 nonalcohol-dependent controls on three versions of DA. These versions, in order of increasing working memory demand, were single alternation (LR), double alternation (LLRR), and asymmetric alternation (LRRR). DA was administered on a personal computer and performance measured by the number of trials taken to reach criterion. RESULTS: Alcohol-dependent participants, compared with the control participants, took more trials to reach learning criterion on DA on all versions when analyzed together (p = 0.002). Performance on DA was also found to deteriorate with increased working memory demands in both groups of participants (p < 0.001). However, the deficits of alcohol-dependent participants were most pronounced on the DA task with moderate (LLRR) as opposed to extreme (LRRR) working memory demands. CONCLUSIONS: The results indicate that both storage and processing demands are necessary for task performance and demonstrate sensitivity of DA to alcohol-related brain injury.

Adult↗

Working memory of school-aged children with a history of febrile convulsions: a population study.

OBJECTIVE: A prospective, population-based, case-control study was performed to ascertain whether febrile convulsion (FC) in early childhood is associated with specific working memory characteristics in school age. METHODS: From a population survey of 4,340 live-birth newborns in Tainan City, Taiwan, 103 children with confirmed FC by age 3 years were followed-up until they were at least 6 years old. Three analogous searching tasks dissociating the mnemonic and executive aspects of performances were administered to 87 of these school-aged children and to 87 randomly selected age-matched control subjects to assess the learning, spatial, and sequential working memory. RESULTS: The FC group performed significantly and consistently better than control subjects on all but one working memory measure, jumping errors. Multivariate analysis using linear regression revealed that the onset of FC before age 1 year was the only significant risk factor for deficits in mnemonic function. Prior neurodevelopmental delay was the only significant risk factor for deficits in executive function. Factors such as socioeconomic status, family predisposition for seizures, complex FC, recurrent FC, and subsequent unprovoked seizures were not risk factors for working memory deficits. CONCLUSION: The authors found that school-aged children with a history of FC demonstrated significantly better mnemonic capacity, more flexible mental processing, and higher impulsivity than their age-matched control subjects. The underlying mechanism for the facilitated working memory function in children with a history of FC needs further delineation.

Child↗

Repetitive transcranial magnetic stimulation dissociates working memory manipulation from retention functions in the prefrontal, but not posterior parietal, cortex.

Understanding the contributions of the prefrontal cortex (PFC) to working memory is central to understanding the neural bases of high-level cognition. One question that remains controversial is whether the same areas of the dorsolateral PFC (dlPFC) that participate in the manipulation of information in working memory also contribute to its short-term retention (STR). We evaluated this question by first identifying, with functional magnetic resonance imaging (fMRI), brain areas involved in manipulation. Next, these areas were targeted with repetitive transcranial magnetic stimulation (rTMS) while subjects performed tasks requiring only the STR or the STR plus manipulation of information in working memory. fMRI indicated that manipulation-related activity was independent of retention-related activity in both the PFC and superior parietal lobule (SPL). rTMS, however, yielded a different pattern of results. Although rTMS of the dlPFC selectively disrupted manipulation, rTMS of the SPL disrupted manipulation and STR to the same extent. rTMS of the postcentral gyrus (a control region) had no effect on performance. The implications of these results are twofold. In the PFC, they are consistent with the view that this region contributes more importantly to the control of information in working memory than to its STR. In the SPL, they illustrate the importance of supplementing the fundamentally correlational data from neuroimaging with a disruptive method, which affords stronger inference about structure-function relations.

Adult↗

Distinct profile of working memory errors following acute or chronic disruption of the cholinergic septohippocampal pathway.

The behavioral effects of two amnestic treatments (intraseptal chlordiazepoxide (CDP) and intraventricular AF64A) were examined in a delayed-nonmatch-to-sample radial-arm maze (DNMTS) paradigm. The types of errors induced by these treatments in this working memory task were assessed to determine how acute and chronic disruptions of the medial septum affect different phases of working memory (encoding, maintenance, retrieval). Rats were initially trained to perform the DNMTS task with a 1-h delay imposed between the training and the testing sessions. The first experiment demonstrated that intraseptal injection of 30 nmoles of CDP did not produce state-dependent learning. Rats were injected immediately following training with CDP or artificial cerobrospinal fluid (CSF; drug vehicle) and then prior to testing with CDP or CSF. Injection of CDP immediately following training (CDP-CSF) impaired performance of the task regardless of whether CDP was also administered before the postdelay test (CDP-CDP). Rats infused with CDP only before the postdelay test (CSF-CDP) exhibited a proactive deficit characterized by intact retention of the predelay information (i.e., arms entered prior to the delay) but impaired performance on the postdelay component (arms entered only after the delay). These data indicate: (i) that state dependency does not explain the working memory deficits induced by intraseptal CDP; (ii) that pretest CDP disrupts the storage and utilization of working memory for current arm selections. The second experiment examined the behavioral effects induced by a permanent disruption of the cholinergic septohippocampal pathway produced by icv injection of the cholinotoxin AF64A. Rats were initially trained on the DNMTS task and then bilaterally injected icv with either AF64A (2.5 nmoles/side) or CSF. AF64A-treated rats exhibited a significant impairment of performance compared to CSF-treated controls. In contrast to the impairment exhibited by CDP-treated rats in Experiment 1, the performance of AF64A-treated rats displayed a deficit in the maintenance/retrieval of information acquired during RAM training and an impairment in ability to store current spatial information in working memory to guide postdelay testing performance. These studies demonstrate that acute and chronic disruptions of the septohippocampal pathway produce distinct profiles of cognitive impairment that should help to reveal the behavioral and neurobiological characteristics of spatial memory.

Animals↗

Intrahippocampal administration of the NO synthase inhibitor L-NAME prevents working memory deficits in rats exposed to transient cerebral ischemia.

A 5-min period of cerebral ischemia increased the number of errors in a working memory task with three-panel runway paradigm, while it had no effect on reference memory errors. The nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), infused into the bilateral dorsal hippocampus at 100 micrograms/side immediately after blood flow reperfusion, significantly reduced the increase in working memory errors expected to occur 24 h after 5 min of ischemia. Intrahippocampal administration of the inactive isomer D-NAME at 100 micrograms/side immediately after reperfusion had no effect on the increase in working memory errors in the ischemic rats. These findings suggest that the mechanism mediated by hippocampal NO synthesis during the early reperfusion phase contributes to the postischemic impairment of working memory.

Amino Acid Oxidoreductases↗

Neurophysiological measures of working memory and individual differences in cognitive ability and cognitive style.

The capacity to deliberately control attention in order to hold and manipulate information in working memory is critical to higher cognitive functions. This suggests that between-subject differences in general cognitive ability might be related to observable differences in the activity of brain systems that support working memory and attention control. To test this notion, electroencephalograms were recorded from 80 healthy young adults during spatial working memory tasks. Measures of task-related neurophysiological and behavioral variables were derived from these data and compared to scores on a test battery commonly used to assess general cognitive ability (the WAIS-R). Subjects who scored high on the psychometric test also tended to respond faster in the experimental tasks without any loss of accuracy. The amplitude of the late positive component of the event-related potential was larger in high-ability subjects, and the frontal midline theta component of the EEG signal was also selectively enhanced in this group under conditions of sustained performance and high working memory load. These results suggest that subjects who scored high on the WAIS-R were better able to focus and sustain attention to task performance. Changes in the EEG alpha rhythm in response to manipulations of task practice and load were also examined and compared between frontal and parietal regions. The results indicated that high-ability subjects developed strategies that made relatively greater use of parietal regions, whereas low-ability subjects relied more exclusively on frontal regions. Other analyses indicated that hemispheric asymmetries in alpha band measures distinguish between individuals with relatively high verbal aptitude and those with relatively high nonverbal aptitude. In particular, subjects with a verbal cognitive style tended to make greater use of the left parietal region during task performance, and subjects with a nonverbal style tended to make greater use of the right parietal region. These results help clarify relationships between task-related brain activity and individual differences in cognitive ability and style.

Adolescent↗

Working memory in Dutch children with reading- and arithmetic-related LD.

The aim of the two studies presented in this article was to examine working memory performance in Dutch children with various subtypes of learning disabilities. The performance of children with reading disabilities (RD) was compared to that of children with arithmetic disabilities (AD), children with both reading and arithmetic disabilities (RAD), and chronological age-matched controls (CA). Measures covered the phonological loop, the visuospatial sketchpad, and the central executive. In both studies, the children with RD showed no working memory deficits whatsoever. Children with AD showed a single impairment on the task tapping working memory for dynamic visual information. Children with RAD performed lower only on the digit span backward task. The failure to replicate the expected working memory deficits in children with reading-related disabilities is discussed.

Child↗

Involvement of arachidonic acid cascade in working memory impairment induced by interleukin-1 beta.

The aim of the present study is to clarify the possible relevance of the arachidonic acid cascade to working memory in rats, by using a three-panel runway apparatus. Interleukin-1 beta, injected bilaterally into the dorsal hippocampus at a dose of 100 ng/side, significantly impaired working memory, and this impairment was attenuated by pretreatment with 10 mg/kg (s.c.) of diclofenac, a cyclooxygenase inhibitor. Working memory was also impaired in rats administered a bilateral intrahippocampal injection of prostaglandin E2, in a dose-dependent manner at 0.01-1 microg/side. Furthermore, an injection of 100 ng/side of interleukin-1 beta significantly increased production of prostaglandin E2 (580 +/- 32 pg to 1142 +/- 101 pg/100 mg wet tissue) in the hippocampus. Taken together, these findings suggest that the activation of the arachidonic acid cascade was causative of the working memory impairment induced by interleukin-1 beta.

Animals↗