Verbal working memory impairment in schizophrenia patients and their first-degree relatives: evidence from the digit span task

OBJECTIVE: The evidence for verbal working memory deficits in schizophrenia has been inconsistent. Few studies have evaluated verbal working memory in the first-degree relatives of schizophrenia patients, who likely share the genetic diathesis for schizophrenia but not the potential confounds associated with chronic mental illness. METHOD: The Wechsler Digit Span Task was used to investigate verbal working memory in 52 schizophrenia patients, 56 of their first-degree relatives, and 73 nonpsychiatric comparison subjects. RESULTS: The nonpsychotic relatives showed no impairment on the forward digit span task, a measure of general attention, but did show impairment on the backward digit span task, a measure of verbal working memory. Schizophrenia patients showed impairment on both the forward and backward digit span tasks. CONCLUSIONS: These results indicate that the forward and backward digit span tasks tap different cognitive abilities that are differentially associated with the diathesis for schizophrenia. Working memory deficits associated with schizophrenia appear to be generalized and not limited to the spatial modality.     

A central executive deficit in patients with Parkinson''s disease.

Eight patients with Parkinson's disease and eight matched controls were tested for concurrent task performance to examine whether Parkinson's disease produces deficits in the coordinating and integrating function of the central executive component of Baddeley's working memory model. Consistent with this prediction, the patients showed a significant decline in performance on a random pursuit tracking task while recalling digit span forward sequences, whereas the controls showed no such change. Performance on the component pursuit and digit span tasks, which did not differ between groups, was equated across subjects by varying the size of a target square and by using individual subjects' digit spans. The patient group also produced poorer word fluency scores and reported higher levels of depression, but there was no significant impairment on the Wisconsin card sort test. There was no association between dual task performance and any psychometric measure, target size, or disease related variables. Baddeley's working memory model is advantageous in providing a rich conceptual basis to explore and characterise cognitive abilities in patients with Parkinson's disease.     

Working memory and FDG–PET dissociate early and late onset Alzheimer disease patients

The aims of this study were to determine the influence of the onset of Alzheimers disease (AD) on 1) memory and cerebral glucose metabolism, 2) the relationships between cognitive performance and cerebral glucose metabolism. Brain metabolism was measured by ¹⁸FDG–PET in 12 early onset AD patients (age < 65 years) and 26 late onset ones (> 65), with comparable mean MMSE scores. Working memory, semantic memory and episodic memory were assessed. Cognitivo–metabolic correlations (CMC) and complementary interregional correlations were performed in order to identify specific neurocognitive processes within each group. Both AD groups performed poorly on all tasks, except digit span in the late onset group. The early onset group performed more poorly than the late onset one on both the digit span and Brown–Peterson Paradigm (BPP) tasks. Temporo–parietal hypometabolism was found in both groups, the left hemisphere being more affected than the right, especially in the early onset patients, who also showed specific left frontal hypometabolism. For the BPP task, the CMC principally involved left frontal areas in the early onset group, and the cerebellum in the late onset one. For the digit span task, they involved cerebellar and occipital regions in the latter. Regarding the digit span, the occipital and cerebellar involvement may have reflected an effective compensatory mechanism in the late onset patients, while high left supramarginal gyrus hypometabolism in the early onset patients may have explained their failure in this task. In the BPP task, the lower performance of the early onset group may have been due to a frontal lobe dysfunction, as suggested by 1) the hypometabolism of this region, 2) the CMC results, 3) the interregional correlations, which indicated greater disruption of the antero– posterior loop.     

首发精神分裂症患者神经认知功能的遗传学分析

目的 探索精神分裂症患者及其亲属共同存在的神经认知功能损害,并对22号染色体上儿茶酚氧位甲基转移酶(COMT)基因和脯氨酸脱氢酶(PRODH)基因的5个候选单核苷酸多态性(SNP)位点进行相关的遗传学分析。方法 采用14个神经心理测验(共29项)对235例首发精神分裂症患者(患者组)、322名未患病亲属(亲属组)和133名正常对照(正常对照组)进行有关智力、注意、记忆、言语功能和执行功能等评定,比较各组间的神经认知功能有无差异,并对上述神经认知功能测验与COMT和PRODH基因的5个候选SNP进行定量性状的传递不平衡测试。结果 (1)患者组所有测验的成绩均差于正常对照组,差异有显著性(P<0.01和P<0.05),而亲属组的记忆、注意、言语功能和执行功能界于患者与正常对照之间;(2)PRODH1 195G/A与即刻逻辑记忆测验(P=0.03)、言语流畅性测验的正确数(P=0.03)和连线测验B的犯规数(P=0.01)相关,PRODH1945G/A与数字符号测验(P:0.01)、连线测验A的错误数(P:0.02)、HANOI塔测验的总分(P=0.01)、威斯康星卡片分类测验(WCST)的总错误数(P=0.01)、WCST的非持续错误数(P:0.02)和WCST的总分类数(P=0.02)相关。结论 精神分裂症患者在记忆、注意、言语功能和执行功能等方面存在广泛的神经认知功能损害,这种损害可能是精神分裂症的遗传“内表     

Neuropsychological correlates of schizophrenic syndromes in patients treated with atypical neuroleptics.

There is widespread evidence that schizophrenic symptomatology is best represented by three syndromes (positive, negative, disorganized). Both the disorganized and negative syndrome have been found to correlate with several neurocognitive dysfunctions. However, previous studies investigated samples predominantly treated with typical neuroleptics, which frequently induce parkinsonian symptoms that are hard to disentangle from primary negative symptoms and may have inflated correlations with neurocognition. A newly developed psychopathological instrument called the Positive and Negative and Disorganized Symptoms Scale (PANADSS) was evaluated in 60 schizophrenic patients. Forty-seven participants treated with atypical neuroleptics performed several neurocognitive tasks.A three-factor solution of schizophrenic symptomatology emerged. Negative symptomatology was associated with diminished creative verbal fluency and digit span backward, whereas disorganization was significantly correlated with impaired Stroop, WCST and Trail-Making Test B performance.Data suggest that disorganization is associated with tasks that demand executive functioning. Previous findings reporting correlations between negative symptomatology and neurocognition may have been confounded by the adverse consequences of typical neuroleptics.     

Performance of Individuals with Left-Hemisphere Stroke and Aphasia and Individuals with Right Brain Damage on Forward and Backward Digit Span Tasks

BACKGROUND: Working memory (WM) limitations have been suggested as a significant source of the linguistic processing deficits observed in individuals with aphasia (IWA). Digits forward (DF) and digits backward (DB) span tasks are frequently used to study WM in both healthy and clinical populations. Unfortunately, only a handful of studies have explored digit span in IWA. AIMS: The purpose of the current study is to measure the DF and DB spans of IWA and compare their digit spans to a group with right brain damage, but no aphasia (RBD). Additionally, DF and DB span is compared within each group to determine if there is indeed a performance differential that may support the idea that DB is a more difficult WM task in these populations. METHODS AND PROCEDURES: Seventeen IWA and 14 individuals with RBD participated in a DF and DB span task. Modifications to the span tasks were implemented to accommodate language deficits. A series of two digits were orally presented to each participant continuing to a maximum of eight digits. There were seven trials per digit series. Participants were asked to point to the correct order of digits on a written 1-9 digit list provided on individual note cards or verbally repeat the numbers if the participant was able to do so. OUTCOMES AND RESULTS: IWA demonstrated shorter digit spans than the RBD group. Both groups performed worse on the DB span tasks than the DF span tasks. CONCLUSIONS: The results are consistent with previous studies suggesting that DB span is shorter than DF span in other populations and that there are differences in performance on digit span tasks between the two groups. The differences between RBD group and IWA may be explained by decreased attentional capacity or inefficient resource allocation in IWA, or alternatively, a deficient phonological loop. Future studies should explore these possibilities.     

Computerized analysis of error patterns in digit span recall

We analyzed error patterns during digit span (DS) testing in four experiments. In Experiment 1, error patterns analyzed from a community sample of 427 subjects revealed strong primacy and recency effects. Subjects with shorter DSs showed an increased incidence of transposition errors in comparison with other error types and a greater incidence of multiple errors on incorrect trials. Experiment 2 investigated 46 young subjects in three test sessions. The results replicated those of Experiment 1 and demonstrated that error patterns of individual subjects were consistent across repeated test administrations. Experiment 3 investigated 40 subjects from Experiment 2 who feigned symptoms of traumatic brain injury (TBI) with 80% of malingering subjects producing digit spans in the abnormal range. A digit span malingering index (DSMI) was developed to detect atypical error patterns in malingering subjects. Overall, 59% of malingering subjects with abnormal digit spans showed DSMIs in the abnormal range and DSMI values correlated significantly with the magnitude of malingering. Experiment 4 compared 29 patients with TBI with a new group of 38 control subjects. The TBI group showed significant reductions in digit span. Overall, 32% of the TBI patients showed DS abnormalities and 11% showed abnormal DSMIs. Computerized error-pattern analysis improves the sensitivity of DS assessment and can assist in the detection of malingering.     

Discrepancy of performance among working memory-related tasks in autism spectrum disorders was caused by task characteristics, apart from working memory, which could interfere with task execution

Working memory performance has been inconsistently reported in autism spectrum disorders (ASD). Several studies in ASD have found normal performance in digit span and poor performance in digit symbol task although these are closely related with working memory. It is assumed that poor performance in digit symbol could be explained by confirmatory behavior, which is induced due to the vague memory representation of number-symbol association. Therefore it was hypothesized that the performance of working memory task, in which vagueness did not cause confirmatory behavior, would be normal in ASD. For this purpose, the Advanced Trail Making Test (ATMT) was used. The performance of digit span, digit symbol and ATMT was compared between ASD and normal control. The digit span, digit symbol and ATMT was given to 16 ASD subjects and 28 IQ-, age- and sex-matched control subjects. The scores of these tasks were compared. A significantly lower score for ASD was found only in digit symbol compared with control subjects. There were no significant difference in digit span and working memory estimated by ATMT. Discrepancy of scores among working memory-related tasks was demonstrated in ASD. Poor digit symbol performance, normal digit span and normal working memory in ATMT implied that ASD subjects would be intact in working memory itself, and that superficial working memory dysfunction might be observed due to confirmatory behavior in digit symbol. Therefore, to evaluate working memory in ASD, tasks that could stimulate psychopathology specific to ASD should be avoided.     

A longitudinal analysis of memory in patients with schizophrenia

Memory deficits are widely reported in patients with schizophrenia, but uncertainties remain about the extent and the longitudinal course of these deficits. Twenty-eight patients with a DSM-IV diagnosis of schizophrenia were tested on multiple aspects of memory at baseline, 9- and 18-month follow-up. Measures included: digit span, the Rivermead Behavioural Memory test (RBMT) battery, the Graded Naming Test (GNT) and several computerized memory tests from the Cambridge Automated Neuropsychological Testing Battery (CANTAB). A group of healthy controls (N=17) was tested on the CANTAB battery at baseline and 9-month follow up. The patients performed significantly poorer than controls on all CANTAB measures; however, there was no difference in change between groups over a 9-month period. Within-group patient comparisons revealed that symptoms reduced significantly over the study period, but had no association with memory. Significant improvements were observed for patients on two verbal memory tasks: the GNT and digit span, but not on any other measure. Interestingly, these were the only two tests on which patients were within normal limits at baseline. This study shows that patients with schizophrenia have deficits in multiple aspects of memory which remain stable over long periods of time. In addition, patients showed a tendency to improve on memory tasks which contained a verbal component.     

Performance of individuals with left hemisphere stroke and aphasia and individuals with right brain damage on forward and backward digit span tasks

Background: Working memory (WM) limitations have been suggested as a significant source of the linguistic processing deficits observed in individuals with aphasia (IWA). Digits forward (DF) and digits backward (DB) span tasks are frequently used to study WM in both healthy and clinical populations. Unfortunately only a handful of studies have explored digit span in IWA.

Aims: The purpose of the current study is to measure the DF and DB spans of IWA and compare their digit spans to a group with right brain damage, but no aphasia (RBD). Additionally, DF and DB span is compared within each group to determine if there is indeed a performance differential that may support the idea that DB is a more difficult WM task in these populations.

Methods & Procedures: A total of 17 IWA and 14 individuals with RBD participated in a DF and DB span task. Modifications to the span tasks were implemented to accommodate language deficits. A series of two digits were orally presented to each participant continuing to a maximum of eight digits. There were seven trials per digit series. Participants were asked to point to the correct order of digits on a written one- to nine-digit list provided on individual note cards or to verbally repeat the numbers if the participant was able to do so.

Outcomes & Results: IWA demonstrated shorter digit spans than the RBD group. Both groups performed worse on the DB span tasks than the DF span tasks.

Conclusions: The results are consistent with previous studies suggesting that DB span is shorter than DF span in other populations and that there are differences in performance on digit span tasks between the two groups. The differences between RBD group and IWA may be explained by decreased attentional capacity or inefficient resource allocation in IWA, or alternatively, a deficient phonological loop. Future studies should explore these possibilities.     

Remitted schizophrenia-spectrum patients with spared working memory show information processing abnormalities

Working memory and information processing abnormalities are often reported in schizophrenia. The aim of this study was to examine visual backward masking (BM) functions in remitted schizophrenia-spectrum patients with spared working memory functions. Seventy-two patients with DSM-IV schizophrenia-spectrum disorders were screened using the Wisconsin Card Sorting Test (WCST) and the digit span forward/backward tasks. Patients with spared WCST and digit span performances were selected and administered a spatial working memory test and two BM procedures (target identification and location). The schizophrenia-spectrum group with spared WCST and digit span performances included individuals with schizophreniform disorder (N=11), schizophrenia (N=2), and schizoaffective disorder (N=2). These patients were clinically remitted and demonstrated spared IQ, normal spatial working memory, and relatively high psychosocial functioning. However, there was a significant impairment in the BM procedure, most prominently in the target location task and at short interstimulus intervals. These results suggest that the BM dysfunction is a trait marker of schizophrenia-spectrum disorders and may be present in the absence of working memory abnormalities. Received: 25 August 2000 / Accepted: 5 February 2001     

Executive function impairment in community elderly subjects with questionable dementia

BACKGROUND: The neurocognitive profile of community-dwelling Chinese subjects with 'questionable' dementia was studied. METHODS: One hundred and fifty-four ambulatory Chinese subjects were recruited from local social centers for the elderly. Each subject was examined using the Clinical Dementia Rating (CDR), the Cantonese version of the Mini-Mental State Examination (CMMSE), the Chinese version of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Category Verbal Fluency Test (CVFT), digit and visual span tests, and the Cambridge Neurological Inventory. The neurocognitive profile of nondemented subjects (CDR 0) was compared with that of subjects with 'questionable' dementia (CDR 0.5). RESULTS: Subjects with 'questionable' dementia were older, and had lower educational levels and global cognitive assessment scores than the controls (CMMSE and ADAS-Cog; t tests, p < 0.001). In addition, they also had significantly lower scores in delayed recall, reverse span, verbal fluency tests and worse performance in complex motor tasks related to executive function (Mann-Whitney tests, p < 0.001). Logistic regression analysis revealed that ADAS-Cog, CVFT, and reverse visual span were significant predictors for the CDR of 'questionable' dementia. CONCLUSION: Aside from memory impairment, executive function deficits were also present in subjects with 'questionable' dementia. To identify groups cognitively at risk for dementia, concomitant assessments of memory and executive function are suggested.     

Age-related working memory decline in patients with Parkinson's disease]

The purpose of this study was to investigate the age-related working memory(WM) decline in patients with Parkinson's disease(PD) using Baddeley's WM model. This model consists of the central executive (CE) and two slave systems, the phonological loop (PL) for the storage of verbal materials, and the visuospatial sketchpad(VSSP) for the storage of visuospatial information. The participants of this study were 22 PD, 11 old (age of 68-78, mean age, 70.5) and age of onset, duration of illness, medication time, and Yahr stage, global cognitive status-matched 11 young(age of 39-58, mean age, 51.5) PD, age- and educational years, global cognitive status-matched 22 normal control (NC), 11 old(age of 65-78, mean age, 70.4) and 11 young(age of 45-57, mean age, 52.4). Mental calculation span of digit sequences, digit forward and backward span, visual memory span were carried out. Age related decline of WM was found in both groups, but processing related differences were revealed between the two groups. NC group showed significant decline with aging in digit backward span. In contrast, in mental calculation span, PD groups showed significant deficit revealed in young PD group and declined significantly with aging and significant decline was not found in digit backward span. In term of the processing and difficulty of WM tasks, digit backward span that needs maintenance of digit sequences and re-ordering, was more difficult than mental calculation that needs maintenance of digit sequences, summation of the digit and updating of the results. There were not significant differences between four groups in digit forward span, visual memory span. The results indicated that the WM span in normal aging declined as task difficulty increased. Their performance decline may be caused by the CE dysfunction. On the other hand, PD showed a characteristic CE deficit observed in mental calculation even in young age and decline with aging. Such decline may be caused by peculiar processing related dysfunction of CE that assumes to be essential deficit of PD.     

Semantic verbal fluency deficit as a familial trait marker in schizophrenia

This study examined neurocognitive deficits as familial vulnerability factors to schizophrenia. Twenty-three Chinese schizophrenic patients, 21 of their non-psychotic siblings and 26 healthy volunteers, matched for age, sex and education, were assessed by using a battery of neurocognitive tests including: Wisconsin Card Sorting Test (WCST), semantic verbal fluency, logical memory, digit span, information, comprehension and similarity. The results showed that siblings had significantly less word output in the verbal fluency test as compared to controls. No significant difference was found between siblings and controls for other tests except that a trend difference was noted for the performance on the similarity test and number of categories completed on the WCST. The verbal fluency abnormality can be considered as a familial trait marker for schizophrenia. Relationships between the residual symptoms after an acute psychotic episode and the magnitude of familial risk were examined. More severe residual symptoms of probands at clinical remission could be predicted by their older age of onset and by better verbal fluency performance in their non-psychotic siblings. This tentatively suggests that patients with a milder genetic form of schizophrenic illness may have a more severe environmental contribution to cerebral insult according to the multifactorial/threshold model. The environmental cerebral insult may cause structural abnormalities leading to incomplete remission of clinical symptoms.     

Memory tests in first-degree adult relatives of schizophrenic patients: a meta-analysis

BACKGROUND: Memory deficits have been clearly demonstrated in schizophrenic patients. However, studies of memory performances in their relatives compared to normal controls provide conflicting results. A meta-analysis was carried out to synthesize all the published data. Unlike previous meta-analyses, which were based on composite scores, we analyzed each memory test separately. This prevents theoretically questionable choices in grouping variables, leads to results with clearer implications for applied research (e.g. the best choice of a test according to its sensitivity) and is more productive in suggesting explanatory hypotheses. METHOD: We initially selected 77 potentially relevant articles, but only 19 met our inclusion criteria. These articles provided data on eight different tasks, from five different memory tests: four tests from the Wechsler Memory Scale (WMS) and the California Verbal Learning Test (CVLT). For each task, we assessed data homogeneity, identified the outliers if any and then estimated effect sizes and tested publication bias using funnel plots. RESULTS: Adult relatives of schizophrenic patients were significantly impaired on most, but not all, tasks. The largest deficits were observed for the verbal paired associates test, the logical stories the digit span forward test and the digit span backward test. We found no significant differences in tasks of delayed recall, when deficits in immediate conditions (reflecting encoding) were taken into account. CONCLUSIONS: Adult relatives of schizophrenic patients have wide but not severe memory impairments. The size of estimated effects suggests that encoding processes are impaired, whereas storage and retrieval processes are relatively unaffected.     

Schizophrenics show spatial working memory deficits.

The present study demonstrates that schizophrenics are impaired on spatial delayed-response tasks, analogous to those that have been used to assess the working memory function of the dorsolateral prefrontal cortex in rhesus monkeys. Schizophrenic patients and two control groups, normal subjects and bipolar psychiatric patients, were tested on the oculomotor version of the memory task, a haptic version of the same task, and two control tasks: a sensory task that did not require working memory and a digit span test. The schizophrenic patients showed marked deficits relative to the two control groups in both the oculomotor and haptic delayed-response tasks. They were not, however, impaired on the digit span test, which taps verbal working memory as well as voluntary attention, and on the sensory control task, in which their responses were guided by external cues rather than by spatial working memory. These findings provide direct evidence that schizophrenics suffer a loss in representational processing and that this deficit is modality independent. These data on spatial working memory add to the growing evidence for involvement of the dorsolateral prefrontal cortex in schizophrenic disease.     

Forward and backward digit span difficulties in children with specific learning disorder

This study examined performance in the forward and backward digit span task of the Wechsler Intelligence Scale for Children–Fourth Edition (WISC–IV) in a large group of children with specific learning disorder (SLD) as compared with a group of typically developing children matched for age and sex. Our results further support the hypothesis that the intellectual difficulties of children with SLD involve working memory in the forward digit span task to a greater extent than in the backward digit span task. The correlation of the two spans with a General Ability Index (GAI) was similar in SLD, and smaller in magnitude than in typically developing children. Despite a GAI within normal range, children with SLD had difficulty with both digit span tasks, but more so for forward span. This pattern was similar for different SLD profiles with clinical diagnoses of dyslexia and mixed disorder, but the impairments were more severe in the latter. Age differences were also investigated, demonstrating larger span impairment in older children with SLD than in younger.     

Short term memory and working memory in blind versus sighted children

There is evidence that blind people may strengthen their memory skills to compensate for absence of vision. However, which aspects of memory are involved is open to debate and a developmental perspective is generally lacking. In the present study, we compared the short term memory (STM) and working memory (WM) of 10-year-old blind children and sighted children. STM was measured using digit span forward, name learning, and word span tasks; WM was measured using listening span and digit span backward tasks. The blind children outperformed their sighted peers on both STM and WM tasks. The enhanced capacity of the blind children on digit span and other STM tasks confirms the results of earlier research; the significantly better performance of the blind children relative to their sighted peers on verbal WM tasks is a new interesting finding. Task characteristics, including the verbal nature of the WM tasks and strategies used to perform these tasks, are discussed.     

Digit repetition performance in patients with focal brain damage

Digit span forward and backward was investigated in well-matched samples of patients with discrete quadrant brain lesions. The incidence of significantly impaired digit repetition performance and the incidence of large forward and backward digit span discrepancies were also studied. Correlational data of digit span performance and various intellectual, memory, and constructional measures was examined. Approximately 60% of all brain-damaged patients showed an impairment of digit span forward, while only 5% showed a similar impairment on the digit span backward task. These data indicate that digit span forward is a more sensitive measure of brain dysfunction from focal brain lesions. No difference was found in the performance of patients with right or left hemisphere lesions; however, the low incidence of aphasia (8%) in this sample may account in part for the relatively adequate performance by the left hemisphere patients. Although the current data regarding visual constructive deficits and impaired ability to repeat digits backward is inconclusive, there did not appear to be a strong relationship between these two functions for these patients. Digit repetition performance does appear to be related to both general intellectual ability and to performance on the Wechsler Memory Scale.     

Executive dysfunction in patients with spinocerebellar ataxia type 3

The aim of this study was to assess the cognitive functions of patients with spinocerebellar ataxia type 3(SCA3). We examined 15 patients with genetically confirmed SCA3 and 15 healthy control subjects matched for age, years of education, and intellectual ability. We administered verbal memory (word recall and word recognition) and executive function tasks (word fluency test, forward and backward digit and visual span tests, Kana Pick-out Test, Trail Making Test, and conflicting instructions and a Go/NoGo task from the Frontal Assessment Battery). We found that patients with SCA3 had significantly lower scores than the healthy control subjects on the word recall, semantic, and letter fluency, and backward digit span tests, while word recognition was well preserved. The other executive function tests showed preserved functions in the SCA3 group, indicating that visual working memory, and attention and inhibition control were not affected. The patients with SCA3 showed impaired word recall and intact word recognition, and accordingly, episodic memory encoding and storage processes in short-term memory were preserved. In category and letter-fluency tests, impairment was attributable to word-retrieval from semantic memory. Impaired verbal working memory may be involved in the retrieval of verbal information from phonological storage by means of continuous subvocal rehearsal, rather than a deficit in initial phonological encoding. Essential executive dysfunction in patients with SCA3 may be due to damage in the cerebellar cortex–ventral dentate nucleus–thalamus–prefrontal cortex circuits, which are involved in strategic retrieval of verbal information from different modes of memory storage.