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PubMed2004

Neural correlates of working memory for sign language.

Eight, early bilingual, sign language interpreters participated in a PET study, which compared working memory for Swedish Sign Language (SSL) with working memory for audiovisual Swedish speech. The interaction between language modality and memory task was manipulated in a within-subjects design. Overall, the results show a previously undocumented, language modality-specific working memory neural architecture for SSL, which relies on a network of bilateral temporal, bilateral parietal and left premotor activation. In addition, differential activation in the right cerebellum was found for the two language modalities. Similarities across language modality are found in Broca's area for all tasks and in the anterior left inferior frontal lobe for semantic retrieval. The bilateral parietal activation pattern for sign language bears similarity to neural activity during, e.g., nonverbal visuospatial tasks, and it is argued that this may reflect generation of a virtual spatial array. Aspects of the data suggesting an age of acquisition effect are also considered. Furthermore, it is discussed why the pattern of parietal activation cannot be explained by factors relating to perception, production or recoding of signs, or to task difficulty. The results are generally compatible with Wilson's [Psychon. Bull. Rev. 8 (2001) 44] account of working memory.

Adult↗
PubMed2006

No differences in performance on test of working memory and executive functioning between healthy elderly postmenopausal women using or not using hormone therapy.

BACKGROUND: On average, ovarian function ceases at the age of 52 years so that estrogen (E) levels are chronically low following the menopause. Numerous studies have found that hormone therapy (HT) helps to protect verbal memory, a hippocampal function. Estrogen receptors are also found in the prefrontal cortex (PFC), suggesting that estrogen may modulate executive and working memory functions, both mediated by the PFC. The possible role of progesterone (P) on executive functions and working memory is unknown. OBJECTIVE: To examine the relationship between neuropsychological performance, age of initiation of HT, and duration of HT use. METHOD: In this cross-sectional study, the neuropsychological performance of 37 postmenopausal women (mean age, 65 years) who used either estrogen-only or sequential E + P (E-alone group)(n = 22) or E + P continuously (n = 15) was compared to that of 28 healthy postmenopausal women matched for age and education who had never used HT. It was hypothesized that the E-only users would perform better then the E + P and the never-users on neuropsychological tests of verbal memory, executive function and working memory. RESULTS: Results showed only minor between-group differences on working memory scores such that the E + P users were slowest to generate a response on the N-Back test of working memory. No group differences on tests of executive functions were found. CONCLUSION: There was no relationship between neuropsychological performance, age of initiation of HT, or duration of HT use.

Affect↗
PubMed2005

Ketanserin attenuates nicotine-induced working memory improvement in rats.

Nicotinic systems have been shown in numerous studies to be important for spatial working memory. Nicotinic systems are certainly not acting alone in the basis of memory function, but act in concert with a variety of other neural systems. Important for these interactions is nicotinic induced release of a variety of neurotransmitters involved in memory function including serotonin (5-HT). We have found that the 5-HT2 receptor antagonist, ketanserin, effectively attenuated nicotine-induced attentional improvement. The current study explored the interaction between nicotinic and serotonergic systems in the performance of a spatial working memory task in the radial-arm maze. Female Sprague-Dawley rats were trained on the win-shift working memory task on the 8-arm radial maze. After 18 sessions of acquisition training the rats were given acute doses of nicotine (0.2 and 0.4 mg/kg), ketanserin (0.5, 1 and 2 mg/kg) or combinations of the two. The vehicle served as the control. As seen in previous studies, nicotine caused a significant improvement in working memory performance as indexed by the number of correct arm entries before the first error (entries to repeat). Ketanserin at the doses tested did not cause a significant effect on choice accuracy, but it did significantly attenuate the improvement caused by the 0.2 mg/kg nicotine dose. The higher 0.4 mg/kg nicotine dose was nearly sufficient to overcome the ketanserin effect. This study shows that, as with attentional function, nicotine-induced working memory improvement is attenuated by the 5-HT2 antagonist ketanserin. Given that many antipsychotic drugs have substantial 5-HT2 antagonist effects, these atypical antipsychotic drugs may reduce the cognitive improvements caused by nicotinic treatments.

Animals↗
PubMed1991

Tetrahydroaminoacridine alleviates medial septal lesion-induced and age-related spatial reference but not working memory deficits.

This study examined the effects of tetrahydroaminoacridine (THA, an anticholinesterase) on water-maze (WM) spatial reference (stable platform location during training) and spatial working memory (reversal of platform location) learning in young intact/medial septal (MS)-lesioned and aged rats. THA (1 or 3 mg/kg, IP) had no effect on reference or working memory performance of young intact rats. MS lesions decreased cholineacetyltransferase activity in the hippocampus and also impaired spatial reference and working memory. THA at 3 mg/kg stabilized MS lesion-induced reference memory performance deficit (path length increase), but was ineffective at 1 mg/kg. THA had no effect on the working memory performance of MS-lesioned rats. Aged rats were impaired in spatial reference and working memory tasks. THA at 3 mg/kg partially stabilized the age-induced spatial reference memory deficits, but was ineffective at 1 mg/kg. THA at either 1 or 3 mg/kg did not alleviate the age-related deficit in the working memory version of WM. The present results suggest that some of the age-related WM deficits may be related to the degeneration of the MS-hippocampus cholinergic system and that THA may be effective in stabilizing the reference memory deficits induced by hippocampal cholinergic dysfunction.

Aging↗
PubMed1998

Working memory in childhood-onset schizophrenia and attention-deficit/hyperactivity disorder.

We investigated verbal and spatial working memory in participants with childhood-onset schizophrenia (N=13), attention-deficit/hyperactivity disorder (ADHD; N=31) and age-matched normal children (N=27). The ages of the participants ranged from 9 to 20 years, with an average age of approx. 14 in all groups. Diagnoses were based on structured interviews (Kiddie-Schedule for Affective Disorders and Schizophrenia) with the children and their parents and made using DSM-III-R criteria. Verbal working memory was assessed by the highest number of digits recalled in forward and backward order on the Digit Span subtest of the Wechsler Intelligence Scale. Results showed that normal children recalled more digits than schizophrenic and ADHD children, who did not differ. Spatial working memory was assessed with the Dot Test of Visuospatial Working Memory: The children were presented with a dot on a page for 5 s and asked to mark its location on a blank page immediately after presentation or 30 s later. A distracter task was used during the delay to prevent verbal rehearsal. The average distance between the target dot and the child's mark in the 30-s condition was shorter for normal than for schizophrenic and ADHD children, who did not differ. Thus, both schizophrenic and ADHD children showed deficits in verbal and spatial working memory. These results suggest that in both disorders, the capacity of the sensory buffers may be diminished, and/or the availability and allocation of resources to the central executive may be limited.

Adolescent↗
PubMed2001

Honig's model of working memory and brain activation: an fMRI study.

The present study investigated changes in neuronal activation with fMRI related to Honig's model of working memory, which is much less studied compared with other working memory models. In contrast to other studies which have applied recognition procedures, the primary aim with the present study was to examine brain activation when subjects had to continuously recall and forget items held in working memory. The results showed that the mid-ventrolateral frontal cortex was particularly activated in the left hemisphere, whereas the mid-dorsolateral frontal cortex was particularly activated in the right hemisphere during execution of the working memory task. The findings are discussed in relation to process- and domain-specific accounts of working memory.

Adult↗
PubMed1999

A neurocomputational theory of the dopaminergic modulation of working memory functions.

The dopaminergic modulation of neural activity in the prefrontal cortex (PFC) is essential for working memory. Delay-activity in the PFC in working memory tasks persists even if interfering stimuli intervene between the presentation of the sample and the target stimulus. Here, the hypothesis is put forward that the functional role of dopamine in working memory processing is to stabilize active neural representations in the PFC network and thereby to protect goal-related delay-activity against interfering stimuli. To test this hypothesis, we examined the reported dopamine-induced changes in several biophysical properties of PFC neurons to determine whether they could fulfill this function. An attractor network model consisting of model neurons was devised in which the empirically observed effects of dopamine on synaptic and voltage-gated membrane conductances could be represented in a biophysically realistic manner. In the model, the dopamine-induced enhancement of the persistent Na+ and reduction of the slowly inactivating K+ current increased firing of the delay-active neurons, thereby increasing inhibitory feedback and thus reducing activity of the "background" neurons. Furthermore, the dopamine-induced reduction of EPSP sizes and a dendritic Ca2+ current diminished the impact of intervening stimuli on current network activity. In this manner, dopaminergic effects indeed acted to stabilize current delay-activity. Working memory deficits observed after supranormal D1-receptor stimulation could also be explained within this framework. Thus, the model offers a mechanistic explanation for the behavioral deficits observed after blockade or after supranormal stimulation of dopamine receptors in the PFC and, in addition, makes some specific empirical predictions.

Dopamine↗
PubMed2006

Aging and the role of working memory resources in visuospatial attention.

Visuospatial attention has been shown to be robust to the effects of increasing age. Nonetheless, models linking individual differences in working memory capacity to attentional performance suggest that older adults may experience disruptions in visuospatial attention under conditions of resource load. Two experiments were conducted to investigate the effects of age and concurrent working memory load on two tasks that have been proposed to require posterior attentional processes. The findings suggest that loading working memory resources selectively disrupts performance on a nonintegrated Stroop task, whereas cue utilization remains intact. In addition, imposing a working memory load delays the deployment of visuospatial attention in both experiments. Regarding the effects of age, findings suggest that older adults can effectively perform both attentional tasks despite working memory load. Age differences did emerge in the time course of cue utilization. Findings point to the resilience of visuospatial attention in aging, even under conditions of significant cognitive load. We discuss these results and their implications for models postulating a role for working memory capacity in attentional behaviors.

Adolescent↗
PubMed2006

Higher-dimensional neurons explain the tuning and dynamics of working memory cells.

Measurements of neural activity in working memory during a somatosensory discrimination task show that the content of working memory is not only stimulus dependent but also strongly time varying. We present a biologically plausible neural model that reproduces the wide variety of characteristic responses observed in those experiments. Central to our model is a heterogeneous ensemble of two-dimensional neurons that are hypothesized to simultaneously encode two distinct stimuli dimensions. We demonstrate that the spiking activity of each neuron in the population can be understood as the result of a two-dimensional state space trajectory projected onto the tuning curve of the neuron. The wide variety of observed responses is thus a natural consequence of a population of neurons with a diverse set of preferred stimulus vectors and response functions in this two-dimensional space. In addition, we propose a taxonomy of network topologies that will generate the two-dimensional trajectory necessary to exploit this population. We conclude by proposing some experimental indicators to help distinguish among these possibilities.

Action Potentials↗
PubMed1998

Dissociation Of working memory from decision making within the human prefrontal cortex.

We tested the hypothesis that cognitive functions related to working memory (assessed with delay tasks) are distinct from those related to decision making (assessed with a gambling task), and that working memory and decision making depend in part on separate anatomical substrates. Normal controls (n = 21), subjects with lesions in the ventromedial (VM) (n = 9) or dorsolateral/high mesial (DL/M) prefrontal cortices (n = 10), performed on (1) modified delay tasks that assess working memory and (2) a gambling task designed to measure decision making. VM subjects with more anterior lesions (n = 4) performed defectively on the gambling but not the delay task. VM subjects with more posterior lesions (n = 5) were impaired on both tasks. Right DL/M subjects were impaired on the delay task but not the gambling task. Left DL/M subjects were not impaired on either task. The findings reveal a cognitive and anatomic double dissociation between deficits in decision making (anterior VM) and working memory (right DL/M). This presents the first direct evidence of such effects in humans using the lesion method and underscores the special importance of the VM prefrontal region in decision making, independent of a direct role in working memory.

Adult↗
PubMed2006

The selective disruption of spatial working memory by eye movements.

In the late 1970s/early 1980s, Baddeley and colleagues conducted a series of experiments investigating the role of eye movements in visual working memory. Although only described briefly in a book, these studies have influenced a remarkable number of empirical and theoretical developments in fields ranging from experimental psychology to human neuropsychology to nonhuman primate electrophysiology. This paper presents, in full detail, three critical studies from this series, together with a recently performed study that includes a level of eye movement measurement and control that was not available for the older studies. Together, the results demonstrate several facts about the sensitivity of visuospatial working memory to eye movements. First, it is eye movement control, not movement per se, that produces the disruptive effects. Second, these effects are limited to working memory for locations and do not generalize to visual working memory for shapes. Third, they can be isolated to the storage/maintenance components of working memory (e.g., to the delay period of the delayed-recognition task). These facts have important implications for models of visual working memory.

Adolescent↗
PubMed2002

Spatial working memory span, delayed response and executive function in schizophrenia.

This study investigated the spatial working memory span (SWMS) as well as the immediate memory span of schizophrenic patients, and examined the contribution of each span to the patients' executive function deficit in the visuospatial domain. SWMS measured the visuospatial working memory capacity that simultaneously processes and stores visuospatial information. Immediate memory span was measured with the spatial span (SS), a variant of Corsi's block-tapping test. A total of 16 patients diagnosed with schizophrenia and 16 normal control subjects participated in the study. SWMS, as well as the forward and backward SS, was significantly reduced in schizophrenia. The SWMS deficit observed in this study and previous findings of deficit in verbal working memory spans suggest that impairment in working memory capacity in schizophrenia is general, and not limited to the verbal domain. Executive function as assessed with the self-ordered pointing task (SOPT) was also impaired in the patients, which is consistent with clinical observations of self-monitoring impairment in schizophrenia. SWMS was able to account for the performance on the SOPT, but its contribution in the patients' impairment did not reach statistical significance. Backward span deficit explained this executive function impairment. SWMS was effective in explaining schizophrenic patients' impaired performance on the spatial delayed response, a prefrontal function task. Implications of the relations observed between the spans and the prefrontal function tasks are discussed.

Adult↗
PubMed2003

Age-related differences in learning disabled and skilled readers' working memory.

This study determines whether age-related deficits in learning disabled (LD) readers' working memory performance reflect delays in retrieval efficiency and/or storage capacity. The study compared LD and skilled readers' working memory performance (N=226) across four age groups (7, 10, 13, and 20) for phonological, visual-spatial, and semantic information under initial (non-cued), gain (cues that bring performance to an asymptotic level), and maintenance conditions (asymptotic conditions without cues). The important results were that LD readers' working memory performance was inferior to skilled readers on verbal and visual-spatial working memory tasks across all age groups and these differences increased on gain and maintenance conditions when compared to initial conditions. These reading group differences remained when age, reading, and mathematics were partialed from the analysis. The results support a general capacity explanation of reading group differences that is not totally dependent on reading skill. These differences in capacity reflect demands placed on both the accessing of new information and the maintenance of old information that extend beyond the phonological system.

Adolescent↗
PubMed1995

Spatial working memory deficits in the relatives of schizophrenic patients.

BACKGROUND: Studies in nonhuman primates provide evidence that intact spatial working memory depends on the integrity of specific areas in the prefrontal cortex. Patients with schizophrenia have been shown to be impaired on spatial working memory tasks. Relatives of schizophrenic patients show a range of cognitive deficits in the absence of clinical symptoms (eg, thought disorder, eye tracking dysfunctions). We predicted that a significant proportion of relatives of schizophrenic patients would show deficits in working memory as measured by a delayed response task. METHODS: In experiment 1, we tested 18 schizophrenic patients, 15 first-degree relatives of schizophrenic patients, and 18 normal control subjects on an oculomotor delayed response task. In experiment 2, we assessed the performance of another group of 12 first-degree relatives of schizophrenic patients and 16 different normal control subjects on a visual-manual delayed response task. RESULTS: Relatives of schizophrenic patients showed significant deficits in working memory on both the oculomotor and visual-manual delayed response tasks. CONCLUSIONS: Some relatives of schizophrenic patients are impaired on tasks that tap spatial working memory and that implicate the prefrontal system. The delayed response paradigm may be useful in elucidating the multidimensionality of the schizophrenic phenotype.

Adult↗
PubMed1997

Lobular patterns of cerebellar activation in verbal working-memory and finger-tapping tasks as revealed by functional MRI.

The lobular distributions of functional activation of the cerebellum during verbal working-memory and finger movement tasks were investigated using functional magnetic resonance imaging (fMRI). Relative to a rest control, finger tapping of the right hand produced ipsilateral-increased activation in HIV/HV [Roman numeral designations based on Larsell's () nomenclature] and HVI and weaker activation in HVIII that was stronger on the ipsilateral side. For a working-memory task, subjects were asked to remember six (high load) or one (low load) visually presented letters across a brief delay. To assess the motoric aspects of rehearsal in the absence of working memory, we asked the subjects to repeatedly read subvocally six or one letters at a rate that approximated the internally generated rehearsal of working memory (motoric rehearsal task). For both tasks, bilateral regions of the superior cerebellar hemispheres (left superior HVIIA and right HVI) and portions of posterior vermis (VI and superior VIIA) exhibited increased activation during high relative to low load conditions. In contrast, the right inferior cerebellar hemisphere (HVIIB) exhibited this load effect only during the working-memory task. We hypothesize that HVI and superior HVIIA activation represents input from the articulatory control system of working memory from the frontal lobes and that HVIIB activation is derived from the phonological store in temporal and parietal regions. From these inputs, the cerebellum could compute the discrepancy between actual and intended phonological rehearsal and use this information to update a feedforward command to the frontal lobes, thereby facilitating the phonological loop.

Adult↗
PubMed1993

Impairment of working memory induced by scopolamine in rats with noradrenergic DSP-4 lesions.

In a working memory task with a three-panel runway set-up, DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine), a noradrenergic neurotoxin, at 50 mg/kg i.p. given 14 days before testing, had no effect on the number of errors (attempts to pass through two incorrect panels of the three-panel gates at four choice points). Working memory errors were significantly increased by scopolamine, a muscarinic receptor antagonist, at 0.32 mg/kg i.p. given 20 min before testing, whereas errors were not affected by the 0.1 mg/kg dose. In rats with noradrenergic DSP-4 lesions, 0.1 mg/kg scopolamine significantly increased the number of working memory errors. However, DSP-4 at 50 mg/kg and scopolamine at 0.1 mg/kg whether they were administered alone or in combination had no effect on reference memory errors. These results suggest that noradrenergic deficits aggravate the working memory impairment induced by blockade of muscarinic receptors.

Animals↗
PubMed2001

Accounting for age differences on the Wisconsin Card Sorting Test: decreased working memory, not inflexibility.

Two experiments examined the role of cognitive inflexibility and reduced working memory in age-related declines on the Wisconsin Card Sorting Test. Both standard scoring procedures and newly developed scores were used to measure each construct, and modifications of the test further evaluated the role of working memory. Results indicated that age differences are not due to cognitive inflexibility but that for a subset of older adults errors are associated with a reduction in the amount of information that can be stored or processed in working memory. These age differences disappear, however, when visual cues provide information about the immediately preceding sort. The authors conclude by proposing a decline in updating working memory as the explanation that can best account for the entire pattern of age differences on this test.

Adult↗
PubMed2005

Selective utilization of spatial working memory resources during stance posture.

While it has been shown that visual imagery tasks interfere with balance control, the neural mechanisms underlying the interference are unclear. Within a healthy young adult population, we employed a dual-task methodology to investigate the role of visual working memory in stance postural control. The employment of specific visual object and visual spatial working memory cognitive tasks facilitated the selective activation of cortically dissociated working memory resources. Challenging postural sets did not significantly impact object working memory performance, but clearly degraded performance on a spatial working memory task, suggesting that interactions between stance postural control and visual working memory are limited to the spatial domain. Results demonstrated no significant effect of the cognitive tasks upon postural stability.

Adult↗