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.     

Clinical and neurocognitive aspects of source monitoring errors in schizophrenia

OBJECTIVE: Source monitoring, an aspect of memory that involves judgments about the origin of information, has been found to be more prone to errors in schizophrenic subjects than in normal persons. To examine the precise nature of such errors and their relationship to clinical and neurocognitive variables, the authors compared schizophrenic and normal subjects. METHOD: Schizophrenic subjects who had been medication free for 1 week (N = 26) and demographically matched normal subjects (N = 21) performed a source monitoring task and were assessed on current psychiatric symptoms, IQ, and frontal lobe functioning. RESULTS: The schizophrenic subjects had normal recognition memory of target words (recognition hits) and a normal generation effect but made more errors than the comparison subjects in identifying the source of target words. Specifically, the schizophrenic subjects made more errors in remembering the source of new and self-generated items, and they tended to attribute items to an external source. In 11 retested subjects, these errors were stable and independent from medication status after a 2-year interval. Secondary analyses suggested that certain source monitoring errors may be associated with hostility and lower IQ. When the effect of IQ was controlled, correlations with frontal dysfunction were not significant. CONCLUSIONS: Schizophrenic subjects make significantly more source monitoring errors than normal subjects, but not because of problems with recognition memory hits or with the generation effect. This tendency may be trait like and may be related to hostility. Lower IQ in schizophrenia plays a partial role in these errors, but frontal dysfunction does not.     

Impaired generation and use of strategy in schizophrenia: evidence from visuospatial and verbal tasks

BACKGROUND: The aim of this study was to investigate mnemonic strategic deficits in schizophrenic patients. METHODS: Analogous tasks were used that required the self-generation of an efficient strategy and its implementation in two domains: visuospatial and verbal. The tasks were given to 20 IQ preserved schizophrenics and 20 matched normal controls. A number of different scores was derived from each task including strategy, short-term memory capacity and perseveration. RESULTS: Overall, the schizophrenic patients were significantly impaired in their ability to generate effective mnemonic strategies on both tasks. In addition, on the visuospatial task there was no difference between the groups on the memory scores, but the schizophrenic patients made significantly more perseverative errors than controls. They were disproportionately worse on the verbal strategy task, showing impairment on memory as well as on strategy scores and were also impaired at semantically classifying the words. Performance was similar to the deficit seen in patients with frontal lobe excisions and Parkinson's disease, in terms of the inability to generate an effective strategy. The deficit on the verbal task was similar to patients with temporal lobe excisions who show impaired verbal memory. However, the pattern differed in the sense that the temporal lobe patients were able to generate effective strategies, unlike the patients with schizophrenia. CONCLUSIONS: High functioning schizophrenic patients are impaired in utilizing visuospatial and verbal mnemonic strategies. By comparing the results with those of neurosurgical excision patients, further evidence is provided for both frontal and temporal lobe involvement in schizophrenia.     

Neuropsychologic findings in cocaine-dependent outpatients

1. Nineteen recently abstinent cocaine-dependent males were compared to 16 control subjects on a battery of neuropsychological tests. 2. The performance of cocaine-dependent subjects was inferior to the control group on tasks assessing higher level verbal skills, and on a task requiring logical sequencing of complex visual stimuli. 3. Cocaine users also performed poorly on a delayed visual memory task and on a verbal generation task, but performed better than the control group on a task assessing simple visual-motor speed. 4. Possible reasons for these findings are discussed, as are the treatment implications of these findings.     

Word and tone working memory deficits in schizophrenia

BACKGROUND: Verbal memory deficits have been reported in many studies of patients with schizophrenia. We evaluated the specificity of these deficits by comparing patients and control subjects on several verbal and nonverbal auditory memory tests. METHODS: Performance of stable, medicated outpatients with DSM-III-R diagnoses of schizophrenia (N = 38) was compared with that of healthy subjects (N = 39) on a word list immediate recall task, tone delayed discrimination tasks, and word and tone serial position tasks. Before memory testing, patients were divided into 2 groups based on their ability to perform normally on a screening test requiring pitch discrimination and sustained attention. RESULTS: The nonverbal tests were more difficult for control subjects than the verbal tests. Despite this, patients who performed normally on the screening test of perception and attention performed normally on both nonverbal tests but had highly significant deficits on both verbal tests (P<.001 and P = .02). Patients who performed poorly on the screening test had highly significant performance deficits on all the memory tests. CONCLUSIONS: One subgroup of patients with schizophrenia has a selective deficit in verbal memory despite normal motivation, attention, and general perceptual function. Another group has deficits in multiple aspects of cognitive function suggestive of failure in early stages of information processing.     

Assessing declarative memory in schizophrenia using Wisconsin Card Sorting Test stimuli: the Paired Associate Recognition Test

The Paired Associate Recognition Test (PART) was developed to measure declarative memory using Wisconsin Card Sorting Test (WCST) stimuli, so that both tasks could be administered during functional neuroimaging to differentiate memory and executive function, and associated frontal and temporal lobe activation in schizophrenia. The current study was designed to compare PART and WCST performance in schizophrenic patients and to examine effects of medication and symptomatology. The PART, WCST, and standard declarative memory tasks were administered to 30 chronic schizophrenic patients and 30 matched healthy control subjects. Supporting task validity was the finding that patients were equally impaired on the PART and the WCST. Neuroleptics did not appear to affect performance. The effect of anticholinergic medication correlated negatively with WCST performance in a small subsample. Severity of schizophrenia-specific symptoms measured at intake on the Brief Psychiatric Rating Scale correlated negatively with performance on the WCST. These results support the application of the PART and WCST in future functional neuroimaging studies.     

Discourse analysis of logical memory recall in normal aging and in dementia of the Alzheimer type.

This study examined the nature of errors in prose recall made in dementia compared with normal aging. Responses by 48 young adults, 47 nondemented older adults, and 70 people with very mild or mild Alzheimer's disease to the Logical Memory subtest of the Wechsler Memory Scale were examined in a propositional analysis. Compared with young adults, healthy older adults showed good immediate recall but deficits in retention over a delay. Demented individuals made errors of omission, not commission, at immediate recall. These errors probably reflect difficulty with attentional control rather than memory per se. In terms of clinical implications, veridical scoring of the Logical Memory subtest provides more sensitive detection of very mild dementia of the Alzheimer type than the current standard criteria for scoring. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Endothelin B receptor-mediated vasoconstriction induced by endothelin A receptor antagonist

BACKGROUND: Capacity limitation theories have proved to be surprisingly resilient in characterizing some of the cognitive deficits in schizophrenia. However, this perspective has not generally been applied to short-term verbal memory tasks. We explored this issue by first attempting to ascertain if gross misallocations of processing resources might explain impairments in short-term memory in schizophrenia on a classic digit span task and in a second study by attempting to determine what effects delay and memory set size had on a divided attention short-term verbal memory paradigm. METHODS: In the first study 16 patients with schizophrenia and 21 normal controls received 40 trials of a three digit task and 20 trials of a six digit span task. As the absolute number of digits presented and duration of presentation in two conditions were identical, subjects thus had equivalent 'opportunities' to make errors if distraction, in the sense of misallocation of cognitive resources, were at the root of poor performance. In the second study 15 patients with schizophrenia and 15 normal controls were tested in conditions in which two, four or six words were presented and in which rehearsal was prevented by an interference task (colour naming) for delays of 5, 10 or 15 s. RESULTS: Patients had disproportionate difficulty on the six digit rather than the three digit condition, suggesting that deficits in the verbal working memory short-term store may not be the result of attentional factors. In the second study, patients' performance was differentially worsened by the interference task, by memory set size (i.e. a capacity limitation) and by delay, a measure of decay rate. CONCLUSIONS: In concert, these studies demonstrate that schizophrenia patients have difficulties on verbal short-term memory span tasks not because of misallocation of resources, but rather because of limitations in 'representational capacity' and maintenance of information over delays.     

Initiation and supervisory processes in schizophrenia and depression

Clinical studies show that schizophrenic and depressive subjects have problems with daily life activities, and neuropsychological studies tend to explain these problems in terms of a dysexecutive syndrome. Verbal fluency and sentence arrangement are tasks considered to focus on two aspects of the dysexecutive syndrome known as initiation and supervision processes, respectively. In this study, we assessed performance in these two tasks in schizophrenia and depression. Twenty-six schizophrenic subjects (chronic schizophrenia, DSM IV definition) were compared with 26 control subjects balanced for sex, age and educational level, and 16 depressive subjects (major depression episode, DSM IV) were compared with 11 similarly balanced control subjects. Switching and clustering scores were evaluated during a semantic fluency task as two components underlying the initiation and organization processes. Capture errors specific to failure of the supervisory system and differences between the number of correct responses in two conditions (valid/invalid) were evaluated as indexes of the supervision process in a sentence arrangement task. In the semantic fluency task, switching scores were significantly lower in the schizophrenic and depressive subjects than in their respective controls. In the sentence arrangement task, only the schizophrenic subjects made significantly more capture errors than their controls and had significantly fewer correct sequences in invalid conditions than in valid conditions. This study shows a dissociation between supervision and initiation processes in two different psychiatric populations. Initiation is impaired, but supervision is preserved in depression, whereas both initiation and supervision are impaired in schizophrenia.     

Object and place memory in the macaque entorhinal cortex

Lesions of the entorhinal cortex in humans, monkeys, and rats impair memory for a variety of kinds of information, including memory for objects and places. To begin to understand the contribution of entorhinal cells to different forms of memory, responses of entorhinal cells were recorded as monkeys performed either an object or place memory task. The object memory task was a variation of delayed matching to sample. A sample picture was presented at the start of the trial, followed by a variable sequence of zero to four test pictures, ending with a repetition of the sample (i.e., a match). The place memory task was a variation of delayed matching to place. In this task, a cue stimulus was presented at a variable sequence of one to four "places" on a computer screen, ending with a repetition of one of the previously shown places (i.e., a match). For both tasks, the animals were rewarded for releasing a bar to the match. To solve these tasks, the monkey must 1) discriminate the stimuli, 2) maintain a memory of the appropriate stimuli during the course of the trial, and 3) evaluate whether a test stimulus matches previously presented stimuli. The responses of entorhinal cortex neurons were consistent with a role in all three of these processes in both tasks. We found that 47% and 55% of the visually responsive entorhinal cells responded selectively to the different objects or places presented during the object or place task, respectively. Similar to previous findings in prefrontal but not perirhinal cortex on the object task, some entorhinal cells had sample-specific delay activity that was maintained throughout all of the delay intervals in the sequence. For the place task, some cells had location-specific maintained activity in the delay immediately following a specific cue location. In addition, 59% and 22% of the visually responsive cells recorded during the object and place task, respectively, responded differently to the test stimuli according to whether they were matching or non-matching to the stimuli held in memory. Responses of some cells were enhanced to matching stimuli, whereas others were suppressed. This suppression or enhancement typically occurred well before the animals' behavioral response, suggesting that this information could be used to perform the task. These results indicate that entorhinal cells receive sensory information about both objects and spatial locations and that their activity carries information about objects and locations held in short-term memory.     

Mnemonic neuronal activity in somatosensory cortex

Single-unit activity was recorded from the hand areas of the somatosensory cortex of monkeys trained to perform a haptic delayed matching to sample task with objects of identical dimensions but different surface features. During the memory retention period of the task (delay), many units showed sustained firing frequency change, either excitation or inhibition. In some cases, firing during that period was significantly higher after one sample object than after another. These observations indicate the participation of somatosensory neurons not only in the perception but in the short-term memory of tactile stimuli. Neurons most directly implicated in tactile memory are (i) those with object-selective delay activity, (ii) those with nondifferential delay activity but without activity related to preparation for movement, and (iii) those with delay activity in the haptic-haptic delayed matching task but no such activity in a control visuo-haptic delayed matching task. The results indicate that cells in early stages of cortical somatosensory processing participate in haptic short-term memory.     

Multiple inputs to episodic memory: Words tell another story.

Seven patients with semantic dementia were asked to recall and recognize 10-word lists of object-name vocabulary preselected as either still "known" (correct picture naming and word-picture matching) or now "unknown" (incorrect picture naming and word-picture matching) to each individual patient. The patients showed a significant advantage for known words in immediate free recall after several learning trials and also in delayed recall and recognition. The majority of errors of commission for known words were semantic, whereas phonological errors, especially blends of target words, were produced in the unknown condition. These findings support claims that (a) multiple inputs from semantic and perceptual systems support episodic memory and (b) success in verbal and nonverbal episodic memory tasks is differentially dependent on semantic and perceptual information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intrusions in Alzheimer's disease in immediate and delayed memory as a function of presentation modality

Young and elderly participants, and participants with Alzheimer's disease (AD) were compared via the suffix paradigm, where a not-to-be-recalled item is appended onto sequences to be immediately recalled. This task was followed by delayed tasks. In immediate recall, AD subjects showed both extralist and suffix intrusions. Recall of auditorily as compared with visually presented stimuli was superior, with the difference increasing in older subjects. The auditory but not the visual suffix produced an end-of-sequence decrement, which was greater in AD than in other groups. After delay, the elderly and young showed virtually perfect performance. The AD participants showed relatively high performance; however, extralist intrusions were frequent, resulting in a relatively low hit rate. As in immediate recall, intrusions showed specificity for AD, and in this paradigm appeared to be a marker differentiating AD and normal subjects. However, the sample size limits the power and generalizability of these findings.     

Cognitive factors in source monitoring and auditory hallucinations

BACKGROUND: In order to elucidate further the cognitive processes underlying auditory hallucinations, an experiment investigating delayed and immediate source monitoring for positive, negative and neutral verbal material was conducted with schizophrenic patients. METHODS: Patients experiencing auditory hallucinations, patients not experiencing auditory hallucinations and normal subjects participated in a word association task, rating their responses for how much a self-generated thought was their own, how controllable and involuntary it was and their confidence in these ratings. A delayed source monitoring test in which subjects had to recall the source (self or experimenter) of the words from the association task was also administered. RESULTS: Hallucinators showed a greater bias towards external attribution of their thoughts compared with both control groups for immediate attributions of source, but not for delayed attributions. Hallucinators showed a bias towards external attribution of emotional material for immediate source monitoring and all subjects showed a bias towards misattribution of positive material to an external source and negative material to an internal source for the delayed source monitoring task. CONCLUSIONS: These findings appear to be most consistent with theories proposing that hallucinations result from an external attributional bias for internal events. The implications of these results for research and practice are also discussed.     

Neuropsychological functioning in HIV-positive African-American women with a history of drug use

This preliminary investigation examined neuropsychological performance in a sample of human immunodeficiency virus (HIV)-positive and HIV-negative African-American women with a history of drug use. The study population was comprised of 10 HIV-negative, 9 asymptomatic HIV-positive, 13 symptomatic HIV-positive, and 10 acquired immunodeficiency virus (AIDS) patients. A neuropsychological battery designed to assess attention, psychomotor processing, verbal memory, and visual memory was administered to participants. No evidence of HIV-related cognitive impairment was found in patients in the early stages of HIV infection. Multivariate analyses of variance revealed significant deficits in psychomotor processing and verbal recall in persons with AIDS. These individuals showed greater difficulty in tasks requiring maintained attention and performed poorly on measures of immediate and delayed verbal recall. In contrast, HIV status was not related to visual memory, verbal recognition, or the number of errors made during a verbal recall task. The pattern of cognitive deficits observed in persons with AIDS resembles that commonly associated with subcortical pathology. The cognitive deficits observed were not related to depression or recentness of drug use.     

Verbal processing deficits in schizophrenia.

The authors reported that a subgroup of schizophrenic patients performed well on a tone serial position task but was impaired on an auditory word serial position task (Wexler, Stevens, Bowers, Cerniak, & Goldman-Rakic, 1998). This study assessed 30 schizophrenic and 32 controls (matched for comparable tone discrimination) on 4 versions of the verbal serial position tasks and 2 tone serial position tasks. Patients performed poorly on all verbal tasks but performed comparably to controls when tones served as stimuli. Proactive interference and visual presentation further compounded the verbal deficits. Deficits persisted with pronounceable nonword stimuli. These findings provide evidence of specific deficits in language-related processing, although the authors could not rule out the possibility that the differential effects that were observed between the tone and word tasks, and particularly among the verbal tasks, may result from differing discriminating power of the different tests. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain activations in schizophrenia during a graded memory task studied with functional neuroimaging

BACKGROUND: Functional neuroimaging experiments have implicated prefrontal cortex (PFC) in memory processes. Several studies of schizophrenic patients have shown failure of activation in the dorsolateral region of PFC (DLPFC). We used a graded memory challenge to characterize functional neuroanatomical differences between schizophrenic and control subjects. The graded manipulation of task demands enabled us to assess group differences in the context of normal and abnormal psychological task performance. METHODS: Memory-related activity was assessed using positron emission tomography in schizophrenic patients and age-matched controls during performance of a graded memory task. Subjects underwent scanning while learning and recalling word lists of variable length. RESULTS: We used a model that assessed linear and nonlinear effects of memory load. Nonlinear group differences in DLPFC activation were observed. Controls showed a steepening slope of DLPFC increase as task demands increased. By contrast, schizophrenic subjects showed initial DLPFC increases that fell away with increasing memory load. The DLPFC response in schizophrenic subjects was closely related to measured task performance. In addition, schizophrenic subjects failed to show task-related decreases in activity in the left superior temporal and inferior parietal gyrus. CONCLUSIONS: Patients with schizophrenia showed a failure in DLPFC activation only in the face of diminished performance measures, suggesting that a full characterization of task-related changes in DLPFC activation must consider performance levels. However, striking failures of deactivation in superior temporal and inferior parietal regions were independent of task performance, possibly reflecting a core abnormality of the condition.     

''Best clinical practice'': assessment of processes of care and of outcomes in the US Military Health Services System

The functioning of working memory in schizophrenic patients according to Baddeley's model was examined in two complementary experiments. Experiment 1 comprised 27 patients and their controls, matched in age and level of education. Of this pool, 20 pairs participated also in Experiment 2. Digit span, reading rate, and immediate serial recall assessed the functioning of the phonological loop. Corsi and pattern span tasks assessed the capacity of visuo-spatial memory. The central executive's ability to monitor two concurrent tasks was evaluated in a dual task paradigm, and its capacity to control action in a random generation task. A preliminary set of analyses showed that the patients' performances were reduced in all tasks explored, except in digit span. This initial pattern changed consistently after controlling for reading rate. While slow and fast reading patients were comparable in demographic and clinical criteria, slow reading patients showed impaired performance in all tasks, whereas fast reading patients exhibited reduced performance in visuo-spatial tasks and in the random generation task only. The state of functioning of working memory in schizophrenia appears, therefore, to vary consistently among the components of the model and is markedly impaired in slow reading patients. The implications of slowness are discussed.     

Working Memory, Task Switching, and Executive Control in the Task Span Procedure.

Four experiments explored the task span procedure: Subjects received lists of 1-10 task names to remember and then lists of 1-10 stimuli on which to perform the tasks. Task span is the number of tasks performed in order perfectly. Experiment 1 compared the task span with the traditional memory span in 6 practiced subjects and found little difference. Experiment 2 compared the task span and the memory span in 64 unpracticed subjects and also found little difference. Experiment 3 compared practice with consistent and varied lists to address retrieval from long-term memory. Experiment 4 manipulated the number of task switches and found that it had little effect on task spans. The results suggest there is no trade-off between storage and task switching, which supports some theories of executive control and challenges others. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Epidural steroids for treating "failed back surgery syndrome": is fluoroscopy really necessary?

Reaction-times were evaluated in 6 parkinsonian patients and 6 normal control subjects using a simple reaction task and 3 choice reaction tasks of differing complexity. Reaction-times were measured as the time from stimulus onset to the onset of electromyographic activity in the responding muscle. Reaction-time was significantly delayed in patients compared to controls in all tasks, but to a greater extent in the more difficult tasks. The relative magnitude of the change, however, was only 4% in the simple reaction task and 8% in the more difficult choice tasks. These results suggest that the deficit in Parkinson's disease is unlikely to represent a defect in preprogramming as suggested by some investigators. Instead, our results indicate a disturbance in the cerebral processing of the auditory stimuli after their occurrence and prior to the initiation of motor activity.