Study of verbal working memory in patients with Parkinson's disease

The authors examined the nature of the working memory deficit in persons with Parkinson's disease (PD). Three hypotheses were tested: a limited storage capacity, an impaired executive component, and a reduction of psychomotor speed. Verbal working memory was assessed in 14 PD patients without dementia and 14 matched control participants. Participants were administered a classical verbal span test, working memory tasks that required either updating or manipulation capacities, and motor and psychomotor speed tasks. Patients' performance was comparable to that of control participants on the verbal span test. However, results on the working memory tasks indicated a deficit in manipulation with normal updating capacities. Motor and psychomotor slowing were found in the patient group, but slowing could not fully account for the impairment observed in the manipulation task. Results indicated that there is a genuine but selective working memory impairment in patients with PD.     

Brain imaging correlates of verbal working memory in children following traumatic brain injury

Neural correlates of working memory (WM) based on the Sternberg Item Recognition Task (SIRT) were assessed in 40 children with moderate-to-severe traumatic brain injury (TBI) compared to 41 demographically-comparable children with orthopedic injury (OI). Multiple magnetic resonance imaging (MRI) methods assessed structural and functional brain correlates of WM, including volumetric and cortical thickness measures on all children; functional MRI (fMRI) and diffusion tensor imaging (DTI) were performed on a subset of children. Confirming previous findings, children with TBI had decreased cortical thickness and volume as compared to the OI group. Although the findings did not confirm the predicted relation of decreased frontal lobe cortical thickness and volume to SIRT performance, left parietal volume was negatively related to reaction time (RT). In contrast, cortical thickness was positively related to SIRT accuracy and RT in the OI group, particularly in aspects of the frontal and parietal lobes, but these relationships were less robust in the TBI group. We attribute these findings to disrupted fronto-parietal functioning in attention and WM. fMRI results from a subsample demonstrated fronto-temporal activation in the OI group, and parietal activation in the TBI group, and DTI findings reflected multiple differences in white matter tracts that engage fronto-parietal networks. Diminished white matter integrity of the frontal lobes and cingulum bundle as measured by DTI was associated with longer RT on the SIRT. Across modalities, the cingulate emerged as a common structure related to performance after TBI. These results are discussed in terms of how different imaging modalities tap different types of pathologic correlates of brain injury and their relationship with WM.     

Interaction of threat and verbal working memory in adolescents

Threat induces a state of sustained anxiety that can disrupt cognitive processing, and, reciprocally, cognitive processing can modulate an anxiety response to threat. These effects depend on the level of cognitive engagement, which itself varies as a function of task difficulty. In adults, we recently showed that induced anxiety impaired working memory accuracy at low and medium but not high load. Conversely, increasing the task load reduced the physiological correlates of anxiety (anxiety‐potentiated startle). The present work examines such threat‐cognition interactions as a function of age. We expected threat to more strongly impact working memory in younger individuals by virtue of putatively restricted cognitive resources and weaker emotion regulation. This was tested by examining the influence of age on the interaction of anxiety and working memory in 25 adolescents (10 to 17 years) and 25 adults (22 to 46 years). Working memory load was manipulated using a verbal n‐back task. Anxiety was induced using the threat of an aversive loud scream and measured via eyeblink startle. Findings revealed that, in both age groups, accuracy was lower during threat than safe conditions at low and medium but not high load, and reaction times were faster during threat than safe conditions at high load but did not differ at other loads. Additionally, anxiety‐potentiated startle was greater during low and medium than high load. Thus, the interactions of anxiety with working memory appear similar in adolescents and adults. Whether these similarities reflect common neural mechanisms would need to be assessed using functional neuroimaging.     

Neurophysiological correlates of verbal and nonverbal short-term memory in children: repetition of words and faces

The neurophysiological correlates of verbal and nonverbal memory have been extensively studied in adults, but comparable investigations of children are limited. A memory paradigm that is well established with adults is the repetition task, which finds a positive shift in the ERP waveform in response to repeated items, called the "repetition effect." This is thought to represent the brain's memory trace for previously seen information and is reported predominantly at midline frontal and parietal electrodes. We recorded ERPs in thirteen 11- to 14-year old children during repetition tasks of words and faces. Performance was better and ERP latencies shorter for the word than the face task. Although a repetition effect similar to adults was seen at parietal electrodes with increased positivity to repeated items, increased negativity was observed at frontal electrodes; this suggests that the neural substrates of recognition memory continue to develop beyond 11 to 14 years of age. The demonstration of a repetition effect in children provides a basis for studying the neural correlates of specific childhood memory deficits.     

Neural oscillations associated with the primacy and recency effects of verbal working memory

For sequential information, the first (primacy) and last (recency) items are better remembered than items in the middle of the sequence. The cognitive operations and neural correlates for the primacy and recency effects are unclear. In this paper, we investigate brain oscillations associated with these effects. MEG recordings were obtained on 19 subjects performing a modified Sternberg paradigm. Correlation analyses were performed between brain oscillatory activity and primacy and recency indices. Oscillatory activity during information maintenance, not encoding, was correlated with the primacy and recency effects. The primacy effect was associated with occipital post-desynchrony, and temporal post-synchrony. The recency effect was associated with parietal and temporal desynchrony. Differences were also observed according to the maintenance strategy. These data indicate that the primacy and recency effects are related to different neural, and likely cognitive, operations that are dependant on the strategy for information maintenance.     

Underpinnings of the costs of flexibility in preschool children: the roles of inhibition and working memory

This study addressed the respective contributions of inhibition and working memory to two underlying components of flexibility, goal representation (as assessed by mixing costs) and switch implementation (as assessed by local costs), across the preschool period. By later preschool age (4 years, 6 months and 5 years, 3 months), both inhibition and working-memory performance were associated with mixing costs, but not with local costs, whereas no relation was observed earlier (3 years, 9 months). The relations of inhibition and working memory to flexibility appear to emerge late in the preschool period and are mainly driven by goal representation.     

Implicit learning in children and adults with Williams syndrome

In comparison to explicit learning, implicit learning is hypothesized to be a phylogenetically older form of learning that is important in early developmental processes (e.g., natural language acquisition, socialization)and relatively impervious to individual differences in age and IQ. We examined implicit learning in a group of children and adults (9.49 years of age)with Williams syndrome (WS)and in a comparison group of typically developing individuals matched for chronological age. Participants were tested in an artificial-grammar learning paradigm and in a rotor-pursuit task. For both groups, implicit learning was largely independent of age. Both groups showed evidence of implicit learning but the comparison group outperformed the WS group on both tasks. Performance advantages for the comparison group were no longer significant when group differences in working memory or nonverbal intelligence were held constant.     

Infantile spasms in two children with Williams syndrome

We describe two children with Williams syndrome and infantile spasms. The diagnosis of Williams syndrome was confirmed by documentation of a deletion of the elastin gene/Williams syndrome region at 7q11.23. The diagnosis of infantile spasms was confirmed through the presence of interictal hypsarrhythmia. This represents one of the first reports of infantile spasms in the Williams syndrome. Am. J. Med. Genet. 71:54–56, 1997. © 1997 Wiley-Liss, Inc.     

Neonatal cerebral abnormalities and later verbal and visuospatial working memory abilities of children born very preterm

As part of a prospective, longitudinal study, 103 very preterm children underwent structural magnetic resonance (MR) imaging at term equivalent age and an assessment of verbal (Digit Span) and visuospatial (Corsi Blocks) working memory at 6 years corrected age. Compared to children born full term (N = 108), very preterm children were characterized by poorer verbal and visuospatial working memory performance. Very preterm children without cerebral abnormalities performed similarly to full-term children. Verbal impairments were largely confined to children with earlier moderate-severe cerebral abnormalities, while children with mild and moderate-severe abnormalities showed greater difficulties in visuospatial working memory. Findings suggest that very preterm children may be particularly vulnerable to visuospatial impairment. They also highlight the role of early neurological disturbance in the evolution of these difficulties.     

Maintenance of real objects and their verbal designations in working memory

The present study investigated the neural correlates of working memory maintenance for real objects in contrast to their verbal designations. For this purpose we employed a delayed match-to-sample task using functional magnetic resonance imaging. The conjunction of load effects for objects and for words revealed a common bilateral network with main foci in the ventrolateral prefrontal cortex and the intraparietal sulcus. Load effect for objects in comparison to load effect for words revealed stronger activation of bilateral precuneus, which suggests the use of mental imagery of objects and object features. The opposite comparison load words versus load objects showed premotor and auditory areas to be activated in association with phonological rehearsal. The bilateral common activation indicates overlapping codes for real-world objects and their verbal designations. Importantly, there is also a dissociation between maintenance of words and objects, which indicates that phonological rehearsal and mental imagery are employed to different degrees.     

Obesity enhances verbal memory in postmenopausal women with Down syndrome

Several lines of evidence suggest that the loss of estrogen after menopause may play a role in cognitive declines associated with Alzheimer's disease (AD). In postmenopausal women, the principal source of estrogen is estrone, which is influenced by body mass index (BMI). Increased BMI in postmenopausal women is associated with higher levels of serum estradiol and estrone. We hypothesized that obesity could have a beneficial effect on cognition with advancing age. We compared the performance of healthy nondemented obese and non-obese women with Down syndrome (DS) on a broad spectrum of cognitive tests. Estrone levels were 66.9% higher in obese than in non-obese postmenopausal women, and 136% higher in obese than in non-obese premenopausal women. Obese postmenopausal women performed significantly better than non-obese women on measures of verbal memory and on an omnibus test of neuropsychological function, but did not differ significantly in verbal fluency, language, praxis or visuospatial functioning. Among premenopausal women, there was no difference in cognitive function between obese and non-obese women. Our results support the hypothesis that higher endogenous estrogen levels after menopause are associated with better performance on verbal memory.     

Sensorineural hearing loss in children and adults with Williams syndrome

Williams syndrome (WS) is a genetic neurodevelopmental disorder, most often accompanied by mild-to-moderate mental retardation. Individuals with WS show unique communication strengths and impairments that are challenging to treat in community, educational, and vocational settings. Many issues regarding characteristics of auditory sensitivity in WS remain to be resolved. Our purpose was to obtain behavioral (screening and pure-tone audiometry) and objective (distortion product otoacoustic emission-DPOAE) measures of auditory system function from a group of 27 individuals with WS, 6-48 years of age. These measures were gathered both at an international professional conference (n = 19) and in a clinic setting (n = 8). In the behavioral screening conditions, 16/19 (84%) of the individuals failed the hearing screening; and in the behavioral diagnostic hearing condition, 6/8 (75%) demonstrated sensorineural hearing loss (SNHL) and 1/8 demonstrated a hearing loss of undetermined type. In the objective DPOAE testing, 19/25 (76%) had DPOAE absolute amplitudes below the 5th percentile for ears with normal hearing [Gorga et al. (1997); Ear Hear 18(6):440-455]. We report SNHL in 14/18 (78%) of school-age children with WS. Post hoc analyses revealed a significant effect for age, suggesting a pattern of progressive hearing loss. An effect size analysis indicated a clinically meaningful difference in the hearing sensitivity between school-aged children and adults in the high frequencies (4,000 and 8,000 Hz). Similar hearing loss phenotype was observed in patients with familial nonsyndromic supravalvular aortic stenosis (SVAS), suggesting that molecular defects in the elastin gene in the pathogenesis of SNHL in WS. This study highlights the importance of early and regular hearing testing for WS patients and suggests that elastin may have a previously unappreciated function in maintaining hearing sensitivity.     

Early linguistic abilities of Italian children with Williams syndrome

Previous studies of linguistic and memory abilities in Italian-speaking children with Williams syndrome (WS) and Down syndrome (DS)are briefly reviewed. New data on linguistic performance of 6 Italian children with WS between 3 and 6 years of age are presented and compared with data on linguistic performance of 6 children with DS selected from a larger sample and matched for chronological age and vocabulary size and of 6 typically developing (TD) younger children matched for mental age and vocabulary size. The language measures also included a parent report of early phrase structure, a naming test, and a sentence repetition task. Analyses revealed that the 3 groups of children were at the same productive vocabulary level, but showed different patterns in sentence production and repetition. Children with WS produced more complete sentences, similar to TD children at the same vocabulary size, whereas children with DS produced more telegraphic and incomplete sentences. The difference between children with DS and those with WS was more marked on the repetition task, suggesting that phonological short-term memory may play a greater role when sentence production is measured through repetition. In addition, qualitative analysis of errors produced in the repetition test revealed interesting differences among the 3 groups. These results from younger children confirm and extend previous findings with older children and adolescents with WS. They further suggest that the apparently spared linguistic abilities of children with WS could emerge as an artifact of comparisons made to children with DS, whose sentence production competence is more compromised relative to other verbal and nonverbal abilities.     

Role of the executive function in the relationship between verbal working memory and long-term information

It is well known that long-term information contributes to verbal working memory. Although the phonological loop is assumed to have an important role in verbal working memory, the processing of long-term information is supposed to occur in another system, and the executive function is presumably involved in this process. Long-term information that affects verbal working memory can be divided into two types of representations: semantic information and long-term phonological knowledge. We used a dual-task method to investigate the role of the executive function in the processing of these two types of representation. We focused on the concreteness effect and the frequency effect, which are assumed to reflect semantic information and long-term phonological knowledge, respectively. The concreteness effect was banished when the executive function was disrupted by focusing on verbal semantic features. The frequency effect remained intact when the executive function was disrupted, while the burden on the phonological loop caused the effect to be decreased. We concluded that the executive function plays a crucial role in the processing of verbal semantic information, but not in the processing of long-term phonological knowledge.     

Assessing the effect of verbal working memory load on visuo-spatial exogenous orienting

Recent reports have suggested that variants in the sortilin-related receptor gene (SORL1) increase the risk of late onset Alzheimer's disease (AD) in Northern European, Hispanic, African-American and Isreali-Arab populations. SORL1 directs trafficking of amyloid precursor protein (APP) and under-expression of SORL1 may lead to over-expression of beta amyloid peptides. Adults with Down syndrome (DS) over-express APP and have early onset and high risk for AD. We investigated the relation of seven variants in the gene for SORL1 to age at onset and risk for AD among 208 adults with DS, 45-70 years of age at baseline. Participants were ascertained through the New York State developmental disability service system and followed at 18-month intervals. Information from cognitive assessments, caregiver interviews, medical record review and neurological examination was used to establish the diagnosis of dementia. Homozygosity for the minor T allele in rs556349 and for the minor C allele in rs536360 was associated with later age at onset and reduced risk of AD (HR=0.26, 95% CI: 0.08-0.86; and HR=0.40, 95% CI: 0.16-0.98, respectively). Mean age at onset was approximately four years later in individuals who were homozygous for those alleles compared with those who had at least one major allele. These findings indicate a modest association of variants in SORL1 with AD. In addition, we did not observe the same alleles to be associated with AD compared with earlier studies, suggesting that these SNPs are in linkage disequilibrium (LD) with the putative functional variants or that expression of the SORL1 gene and hence its interaction with APP might be modified by the extremely high levels of APP characteristic of Down syndrome. Thus, further studies are needed to identify functional variants that influence risk for AD in this uniquely vulnerable population.     

Assessing the effect of verbal working memory load on visuo-spatial exogenous orienting

The aim of this study was to assess whether or not loading verbal working memory (WM) affects the exogenous orienting of visuo-spatial attention. Visuo-spatial exogenous orienting was measured under low/high WM load conditions by means of an orthogonal spatial cuing paradigm. Participants had to discriminate the elevation (up versus down) of a visual target preceded by a peripheral spatially-nonpredictive visual cue presented on either the left or right. This elevation discrimination task was carried out in-between a verbal WM test, in which a sequence of six digits (to be remembered for report at the end of the trial) was presented either in numerically ascending or random order (i.e., low and high load conditions, respectively). Participants made significantly more recall errors in the high load than in the low load condition, demonstrating that the verbal WM load manipulation had been effective. However, WM load did not interact with visuo-spatial exogenous orienting (i.e., comparable cuing effects were reported in both load conditions). These results are consistent with the view that peripheral visual onsets automatically capture spatial attention, regardless any concurrent increase of verbal WM load.     

Role of anterior cingulate cortex during semantic coding in verbal working memory

The relationship between working memory and long-term memory was one of the main problems in recent studies of working memory. As part of this problem, we examined the neural substrates that sustain the semantic coding process in verbal working memory using fMRI. In past experiments, we behaviorally explored whether central executive plays an important role in the process of semantic coding; thus, we especially focused on the function of anterior cingulate cortex (ACC) that is assumed to form the main neural basis of central executive. We accomplished our purpose by examining the concreteness effect reflecting semantic information. The ACC was strongly activated under the Concrete condition in contrast to the Abstract condition. Based on this result, we argue that the ACC is responsible for the semantic coding process in verbal working memory.     

Patterns of verbal long-term and working memory performance reveal deficits in strategic processing in children with frontal infarcts related to sickle cell disease

Frontal brain regions are thought to mediate strategic processes that facilitate memory. We hypothesized that children with frontal cerebral infarcts related to sickle cell disease (SCD) would exhibit impairments in long-term and working memory as a result of disruptions in strategic processing. Word-list learning and digit span tasks were used to assess verbal memory and strategic processing in 21 children with SCD without infarcts (controls) and in 10 children with SCD with frontal infarcts. On the word-list learning task, children with frontal infarcts performed more poorly in terms of learning and free recall, although recognition and cued recall were adequate; this pattern suggested intact encoding and storage with impaired retrieval. Children with frontal infarcts performed more poorly on backward digit span, although forward digit span was adequate; this pattern suggested intact maintenance with impaired manipulation of information in working memory. Overall, these findings support the notion that disruptions in strategic processing contribute to memory impairments in children with frontal infarcts.