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PubMed2005

Catechol-O-methyltransferase (COMT) genotypes and working memory: associations with differing cognitive operations.

BACKGROUND: Catechol-O-methyltransferase (COMT) is a strong candidate gene for schizophrenia and cognitive functions disrupted in this disorder. This report examines the relation of COMT genotypes to performance on a battery of working memory tests differing in the cognitive operations to be performed on the material. METHODS: A large sample of 402 healthy adults were tested on four working memory tests: Spatial Delayed Response (SDR), Word Serial Position Test (WSPT), N-back, and Letter-Number Sequencing. A subsample (n = 246) was tested on the Wisconsin Card Sorting Test (WCST). A saliva swab was used to obtain DNA from all participants. RESULTS: Letter-Number Sequencing, which requires both storage and manipulation of information, was the only working memory test that showed expected differences among COMT genotypes, with the met/met group showing the best performance and the val/val group the poorest performance. As in previous studies, the met/met group also performed better than the val/val group on the WCST. CONCLUSIONS: COMT genotypes were not associated with performance on tests measuring simple storage, maintenance of temporal order or updating of information in working memory. Genotype differences in Letter-Number Sequencing and WCST suggest that higher-order components of processing (e.g., mental manipulation) are more closely related to this gene.

Adolescent↗
PubMed2000

Synaptic mechanisms and network dynamics underlying spatial working memory in a cortical network model.

Single-neuron recordings from behaving primates have established a link between working memory processes and information-specific neuronal persistent activity in the prefrontal cortex. Using a network model endowed with a columnar architecture and based on the physiological properties of cortical neurons and synapses, we have examined the synaptic mechanisms of selective persistent activity underlying spatial working memory in the prefrontal cortex. Our model reproduces the phenomenology of the oculomotor delayed-response experiment of Funahashi et al. (S. Funahashi, C.J. Bruce and P.S. Goldman-Rakic, Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. J Neurophysiol 61:331-349, 1989). To observe stable spontaneous and persistent activity, we find that recurrent synaptic excitation should be primarily mediated by NMDA receptors, and that overall recurrent synaptic interactions should be dominated by inhibition. Isodirectional tuning of adjacent pyramidal cells and interneurons can be accounted for by a structured pyramid-to-interneuron connectivity. Robust memory storage against random drift of the tuned persistent activity and against distractors (intervening stimuli during the delay period) may be enhanced by neuromodulation of recurrent synapses. Experimentally testable predictions concerning the neural basis of working memory are discussed.

Animals↗
PubMed1995

Phonological working memory and speech production in preschool children.

This study investigates whether phonological working memory is associated with spoken language development in preschool children. Assessments were made of speech corpora taken from 3-year old children grouped in terms of their phonological memory abilities. Both quantitative and qualitative indices of the children's spontaneous speech output were taken in a structured play session. Significant differences were found, with children of good phonological memory abilities producing language that was more grammatically complex, contained a richer array of words, and included longer utterances than children of poor phonological memory abilities. The possible mechanisms by which phonological working memory skills are linked to the production of speech are considered.

Age Factors↗
PubMed2004

Impaired decision making related to working memory deficits in individuals with substance addictions.

This study examined whether individuals with substance dependence (ISDs) show impairments in working memory and whether there is a relationship between their impairments in decision making as measured by the gambling task (GT) paradigm and working memory as measured by a delayed nonmatching to sample (DNMS) task. Using the GT, 11% of healthy control participants and 61% of ISDs opted for choices with high immediate gains in spite of higher future losses. For the ISDs and controls with equal GT impairments, the ISDs performed significantly lower than controls on the DNMS task. The nonimpaired ISDs on the GT also performed significantly worse than matched controls on the DNMS task. The DNMS task deficit in ISDs was across all delay times, suggesting the deficit may lie in the "executive" process of working memory, which supports earlier findings (E. M. Martin et al., 2003). The authors suggest that the prefrontal cortex hosts multiple distinct mechanisms of decision making and inhibitory control and that ISDs may be affected in any one or combination of them.

Adult↗
PubMed2003

The reliability and stability of verbal working memory measures.

The psychometric properties of several commonly used verbal working memory measures were assessed. One hundred thirty-nine individuals in five age groups (18-30, 50-59, 60-69, 70-79, and 80+ years) were tested twice (Time I and Time II) on seven working memory span measures (alphabet span, backward digit span, missing digit span, subtract 2 span, running item span, and sentence span for syntactically simple and complex sentences), with an interval of approximately 6 weeks between testing. There were significant effects of age on all but two of the tasks. All the measures had adequate internal consistency. Correlations between performances at Time I and Time II were significant for all the tasks, other than the missing digit span task. The magnitude of the correlations was similar across the age groups and ranged from .52 to .81. Classification of subjects into discrete memory span groups on the basis of a single measure was highly inconsistent across testing sessions and tasks. Classification into upper and lower quartiles was more stable than using a cutoff score for group membership or than classification into high-, medium-, and low-span groups. Correlational analyses showed that there was a moderate relationship between performances on many of the span tasks. Confirmatory factor analysis suggested that six of the seven tasks reflected a common factor. Both test-retest reliability and stability of classification improved when a composite measure reflecting performance on several tasks was used.

Adult↗
PubMed2004

Working memory components in written sentence generation.

College students wrote either simple or complex sentences using 2 prompt nouns while components of working memory were distracted with a concurrent task. Loads on the visual and spatial components of working memory (retain a shape) and verbal component (retain 3 or 6 digits) were compared with a no-load control. Only the 6-digit load reliably reduced sentence length relative to the control, suggesting that unimpeded sentence generation requires verbal working memory. The sentence length effect may arise from a failure to retrieve and maintain lexical representations during grammatical encoding. Memory load had no effect on grammatical and spelling errors, implying that syntactic and orthographic processing were undisturbed. Other possibilities locate the difficulty in planning conceptual content or in phonological encoding, but some evidence speaks against them.

Choice Behavior↗
PubMed1997

Effects of schizophrenia and aging on pupillographic measures of working memory.

The amount of cognitive resources used to perform a task can be indexed as changes in pupil size. In a previous study, we examined pupillary response measures of slave store and central executive cognitive resources during a working memory task and found abnormally reduced utilization of these resources in schizophrenia. In the present study, multiple regression analyses were performed to examine the independent and combined effects of aging and schizophrenia on pupillary response and recall measures in a larger sample of community-dwelling schizophrenia patients. Schizophrenia was associated with a significant decline in working memory capacity, and an additional moderate decline was associated with aging, but these two factors did not interact. Baseline pupil size was significantly correlated with symptom severity, independent of medication. However, pupillary responses evoked by the working memory task and recall scores were not related to symptom severity. Results were consistent with an additive, rather than a synergistic, relationship between aging and schizophrenia, and suggested that working memory impairment in noninstitutionalized outpatients with schizophrenia may remain stable across symptom status and across the life span.

Adult↗
PubMed2005

The septohippocampal cholinergic system and spatial working memory in the Morris water maze.

The objective of the present study was to determine whether a systematic optimization of Morris water maze (mwm) testing parameters could reveal a significant role of the septohippocampal cholinergic system in spatial working memory. Young adult rats were lesioned using 192 IgG-saporin infused bilaterally into the medial septum. Lesions were near complete as measured by choline acetyltransferase (ChAT) activity and immunohistochemistry. Behavioral testing was performed in three phases. In the first, lesioned and unlesioned rats were trained in the mwm focusing on working memory, which was tested using novel platform locations daily. In the second phase, the optimal locations were retested with increasing intertrial intervals (ITI). In the third phase, intracerebroventricular infusions of nerve growth factor (NGF) were employed to enhance cholinergic activity of the unlesioned rats and potentially further separate group performance. Neither the standard or increased ITI resulted in a consistent significant difference in spatial working memory between groups. In addition, NGF treatment also failed to induce a significant difference in behavioral performance. In conclusion, impairments in working memory as assessed by the mwm could not be revealed despite a greater than 90% loss of hippocampal ChAT and the use of optimal testing parameters and NGF treatment.

Animals↗
PubMed2002

Effects of excitotoxic median raphe lesion on working memory deficits produced by the dorsal hippocampal muscarinic receptor blockade in the inhibitory avoidance in rats.

The experiments investigated the interactions between median raphe nucleus (MRN) serotonergic and septo-hippocampal muscarinic cholinergic systems in the modulation of forming and storing performances of working memory. Rats with ibotenic acid-induced MRN-lesion bilaterally received scopolamine (2-4 microg/each side) infusion into the dentate gyrus of the dorsal hippocampus and were tested in a single trial step-through inhibitory avoidance. Initial preference to the dark compartment (escape latency) was taken as the measure of non-mnemonic behaviours and response latency to enter the dark compartment immediately after the foot-shock was used to measure working memory. The high-dose scopolamine infusion 10 min before the training decreased escape latencies in the sham-lesioned rats, whereas had no effect in the MRN-lesioned rats. Although MRN lesion per se did not alter response latency, it alleviated pre-training scopolamine-induced decrease, but aggravated post-training scopolamine-induced reduction in this parameter. These results suggest that the antagonistic interactive processes between MRN-serotonergic and hippocampal cholinergic systems modulate non-mnemonic component of working memory formation, whereas the storing performance of working memory is modulated by the synergistic interactions between these systems in the hippocampus, mainly in the dentate gyrus.

Animals↗
PubMed2001

Some measures of verbal and spatial working memory in eight- and nine-year-old hearing-impaired children with cochlear implants.

OBJECTIVE: The purpose of this study was to examine working memory for sequences of auditory and visual stimuli in prelingually deafened pediatric cochlear implant users with at least 4 yr of device experience. DESIGN: Two groups of 8- and 9-yr-old children, 45 normal-hearing and 45 hearing-impaired users of cochlear implants, completed a novel working memory task requiring memory for sequences of either visual-spatial cues or visual-spatial cues paired with auditory signals. In each sequence, colored response buttons were illuminated either with or without simultaneous auditory presentation of verbal labels (color-names or digit-names). The child was required to reproduce each sequence by pressing the appropriate buttons on the response box. Sequence length was varied and a measure of memory span corresponding to the longest list length correctly reproduced under each set of presentation conditions was recorded. Additional children completed a modified task that eliminated the visual-spatial light cues but that still required reproduction of auditory color-name sequences using the same response box. Data from 37 pediatric cochlear implant users were collected using this modified task. RESULTS: The cochlear implant group obtained shorter span scores on average than the normal-hearing group, regardless of presentation format. The normal-hearing children also demonstrated a larger "redundancy gain" than children in the cochlear implant group-that is, the normal-hearing group displayed better memory for auditory-plus-lights sequences than for the lights-only sequences. Although the children with cochlear implants did not use the auditory signals as effectively as normal-hearing children when visual-spatial cues were also available, their performance on the modified memory task using only auditory cues showed that some of the children were capable of encoding auditory-only sequences at a level comparable with normal-hearing children. CONCLUSIONS: The finding of smaller redundancy gains from the addition of auditory cues to visual-spatial sequences in the cochlear implant group as compared with the normal-hearing group demonstrates differences in encoding or rehearsal strategies between these two groups of children. Differences in memory span between the two groups even on a visual-spatial memory task suggests that atypical working memory development irrespective of input modality may be present in this clinical population.

Audiometry, Pure-Tone↗
PubMed2007

On the relative role of inhibition in age-related working memory decline.

In this cross-sectional study, the mediating role of inhibition relative to speed in age-related working memory decline on different tasks was investigated. It was hypothesized that the role of inhibition is marginal or absent in a relatively "passive" or simple working memory task, but present in a relatively "active" or complex task in which the processing, rather than the storage capacity of working memory, is addressed. This hypothesis was tested with a structural equation model that was fitted on a subsample (N = 213) of the Maastricht Aging Study (MAAS). The first trial of the Verbal Learning Test (VLT) served as the passive test and the Self-Paced Auditory Serial Addition Task (SPASAT) as the active test. Results showed that the role of inhibition was absent in predicting VLT performance, whereas it was comparable to the role of speed in predicting SPASAT performance. These findings suggest a relative, task-dependent role of inhibition in explaining age-related memory decline.

Adult↗
PubMed2005

Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory.

Previous studies have claimed that weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex that can be more pronounced than cortical modulation induced by transcranial magnetic stimulation, but there are no studies that have evaluated the effects of tDCS on working memory. Our aim was to determine whether anodal transcranial direct current stimulation, which enhances brain cortical excitability and activity, would modify performance in a sequential-letter working memory task when administered to the dorsolateral prefrontal cortex (DLPFC). Fifteen subjects underwent a three-back working memory task based on letters. This task was performed during sham and anodal stimulation applied over the left DLPFC. Moreover seven of these subjects performed the same task, but with inverse polarity (cathodal stimulation of the left DLPFC) and anodal stimulation of the primary motor cortex (M1). Our results indicate that only anodal stimulation of the left prefrontal cortex, but not cathodal stimulation of left DLPFC or anodal stimulation of M1, increases the accuracy of the task performance when compared to sham stimulation of the same area. This accuracy enhancement during active stimulation cannot be accounted for by slowed responses, as response times were not changed by stimulation. Our results indicate that left prefrontal anodal stimulation leads to an enhancement of working memory performance. Furthermore, this effect depends on the stimulation polarity and is specific to the site of stimulation. This result may be helpful to develop future interventions aiming at clinical benefits.

Adult↗
PubMedDate not supplied

Correlation between inhibition, working memory and delimited frontal area blood flow measure by 99mTc-Bicisate SPECT in alcohol-dependent patients.

Recently detoxified non-neurological alcoholic patients appear to be impaired in cognitive tasks measuring inhibitory processes as well as working memory (involving storage and manipulation of information). The aim of this study was to investigate in alcoholic participants the relationship between these two cognitive functions and regional cerebral blood flow (rCBF) studied at rest in regions of interest selected on the basis of recent PET studies which explored inhibitory and working memory in normal subjects. Twenty non-neurological alcoholic patients and 20 normal volunteers were selected for a neuropsychological exploration, including assessment of inhibition processes (by means of the Hayling test) and working memory (by means of the Alpha-span task). rCBF of alcoholics was also evaluated with a semi-quantitative method using a 99mTc-Bicisate single photon emission computed tomography (SPECT) procedure. Alcoholic patients performed worse than controls in the alphabetical condition of the Alpha-span task (involving manipulation and storage of information), and on the Hayling test. Significant correlation emerged between inhibition performance and both the bilateral inferior (left BA 47, r = -0.40; right BA 47, r = -0.599) and median frontal gyrus (left BA 10, r = -0.55; right BA 10, r = -0.59), but not with the region of reference (occipital/cerebellum, r = -0.13). Coordination of storage and manipulation was correlated with bilateral median frontal (left BA 10/46, r = -0.50; right BA 10/46, r = -0.45), but not with bilateral parietal area (left BA 7, r = -0.12, right BA 7, r = -0.18). These results suggest a relationship between inhibition and working memory deficits in alcoholic patients, and regional rCBF measured in frontal areas. Clinical implications of these data related to alcohol relapse are discussed.

Alcohol Drinking↗
PubMed2002

Maintenance and manipulation in spatial working memory: dissociations in the prefrontal cortex.

Two experiments were conducted to compare thec ries of the functional organization of spatial working memory within the human prefrontal cortex. In Experiment I, memory set size for locations was parametrically varied, allowing for the assessment of BOLD signal across maintenance requirements. In the sec ond experiment, manipulation of spatial information held in working memory was contrasted with simple maintenance of that information. Both experiment evoked significant activity in a distributed spatia working memory network. Although dorsolateral prefrontal activation increased monotonically with memory set size, this region was differentially engaged in task conditions involving explicit manipulation of in ternal representations. Activation in the superior frontal sulcal region was associated with maintenance of spatial information, increasing with memory se size. In contrast, ventrolateral prefrontal activation was present only at the highest memory set size, possibly due to the differential use of organizational strategies with more complex stimuli. These results sup port claims that the dorsolateral prefrontal cortex is involved in the manipulation of internal representa tions and that the superior frontal sulcal region is involved in the maintenance of spatial information but they suggest a complex role for the ventrolatera prefrontal region.

Algorithms↗
PubMed2005

Neuropsychological performance in schizotypal personality disorder: importance of working memory.

BACKGROUND: Cognitive deficits consistently have been reported in schizophrenia patients and in patients with schizotypal personality disorder. For this study, the authors wanted to identify which of the domains of cognitive impairment represent "core" deficits of schizophrenia, comparing subjects with schizotypal personality disorder to two comparison groups: healthy volunteers and patients with personality disorders unrelated to schizophrenia. METHOD: Three groups completed a neuropsychological battery: patients with DSM-III-R schizotypal personality disorder (N=82); patients with DSM-III-R personality disorders unrelated to schizophrenia (i.e., a personality disorder other than schizotypal, schizoid, or paranoid [N=44]); and healthy volunteers (N=63). The battery included the California Verbal Learning Test, Trailmaking Test parts A and B, the Dot test of working memory, the Stroop Color and Word Test, the Paced Auditory Serial Addition Test, the WMS visual reproduction test, and the WAIS-R vocabulary and block design. RESULTS: Normative standards for performance that controlled for age, gender, and education were created from the scores of the healthy volunteers. Overall, schizotypal personality disorder patients performed significantly worse than the healthy volunteers and those with personality disorders unrelated to schizophrenia. Specifically, patients with schizotypal personality disorder demonstrated impaired performance on the Paced Auditory Serial Addition Test, WMS visual reproduction test, Dot test, and California Verbal Learning Test. In addition, in a regression analysis, performance on the Paced Auditory Serial Addition Test demonstrated the largest effect size. Indeed, it accounted for unique variance above and beyond all other cognitive measures, since controlling for Paced Auditory Serial Addition Test performance abolished group differences across all other measures. CONCLUSIONS: Patients with schizotypal personality disorder demonstrated moderate cognitive impairment compared with healthy volunteers (significant for seven out of 11 measures). These differences reached statistical significance for tasks of working memory, episodic memory, and delayed recall. Working memory performance accounted for the group differences. This study supports the view that working memory represents a core deficit of schizophrenia spectrum disorders.

Adult↗
PubMed1995

Bidirectional modulation of scopolamine-induced working memory impairments by muscarinic activation of the medial septal area.

The hypotheses that the medial septal area (MSA) is critical for working memory and that MSA neural activity is positively regulated by cholinergic inputs leads to two testable predictions: (1) working memory can be bidirectionally modulated by muscarinic manipulations of the MSA and (2) muscarinic activation of the MSA can enhance memory under conditions of mnemonic impairment. Memory was assessed by T-maze spatial alternation following intraseptal infusion of muscarinic drugs in rats pretreated with intraperitoneal (IP-) injections of scopolamine. Scopolamine dose-dependently impaired working memory and shifted the hippocampal theta activity to a higher peak frequency. Intraseptal scopolamine mimicked the behavioral effects of IP-scopolamine, and intraseptal carbachol appeared to reverse both the behavioral and physiological effects of IP-scopolamine. The results indicate that the amnestic effect of antimuscarinic drugs may be due to an interaction in the MSA and that conditions of memory impairment may be alleviated by selective muscarinic activation of the MSA.

Animals↗
PubMed1994

Intrahippocampal administration of a glycine site antagonist impairs working memory performance of rats.

The effects of 7-chlorokynurenic acid, an antagonist at the glycine site associated with the NMDA receptor/channel complex, on memory functions were investigated using a three-panel runway task. In a working memory task, 7-chlorokynurenic acid at a dose of 3.2 micrograms/side, injected bilaterally into the dorsal hippocampus, significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points). The working memory deficit induced by intrahippocampal 7-chlorokynurenic acid (3.2 micrograms/side) was reversed by concurrent injection (32 micrograms/side) of D-serine, the glycine site agonist. In a reference memory task, 7-chlorokynurenic acid had no effect on the number of errors when injected into the hippocampus at doses up to 3.2 micrograms/side. These results suggest that activation of the hippocampal glycine site coupled to the NMDA receptor is required for working memory function in rats.

Animals↗
PubMed1995

Working memory following improvements in articulation rate in children with cerebral palsy.

It has been postulated that rehearsal rate is the primary determinant of working memory capacity for verbal material (Baddeley et al., 1975). A previous study of normal control children and children with spastic diplegic cerebral palsy (SDCP) suggested that covert rather than overt rehearsal rate determines working memory capacity (White et al., 1994). In the current study, a subset of SDCP children who received a surgical treatment to relieve spasticity were retested on measures of articulation rate and memory span. A subset of control children from the original study were also retested. The SDCP group showed improvements in articulation rate at follow-up, though memory span did not change and was again equivalent to that of controls. These findings indicate that increases in articulation rate are not necessarily accompanied by improvements in memory span, and provide additional evidence that working memory capacity may be determined by covert rather than overt articulatory rehearsal.

Articulation Disorders↗