Working Memory In Patients Research Articles

Neural correlates of working memory dysfunction in first-episode schizophrenia patients: An fMRI multi-center study

Working memory dysfunction is a prominent impairment in patients with schizophrenia. Our aim was to determine cerebral dysfunctions by means of functional magnetic resonance imaging (fMRI) in a large sample of first-episode schizophrenia patients during a working memory task. 75 first-episode schizophrenia patients and 81 control subjects, recruited within a multi-center study, performed 2- and 0-back tasks while brain activation was measured with fMRI. In order to guarantee comparability between data quality from different scanners, we developed and adopted a standardized, fully automated quality assurance of scanner hard- and software as well as a measure for in vivo data quality. After these quality-control measures had been implemented, 48 patients and 57 controls were included in the final analysis. During attention-related processes, even when the performance between patients and controls was comparable, there was a recognizable emergence of cerebral dysfunctions with hypoactivations in the ventrolateral prefrontal cortex (VLPFC), in the superior temporal cortex and in the thalamus. During working memory performance, parietal hypoactivations, especially in the precuneus, were prominent and were accompanied by poorer performance in patients. A hyperfrontality emerged in the ventrolateral prefrontal cortex. Hence, results point to a dysfunctional ventrolateral prefrontal–parietal network during working memory in patients, suggesting impairments in basic functions such as retrieval, storage and maintenance. The brain activation pattern of this large and significant sample of first-episode schizophrenia patients indicates an imbalanced system failing to adjust the amount of brain activity required in the cerebral network involved in attention and working memory.

Spatial working memory deficit correlates with disorganization symptoms and social functioning in schizophrenia

Both spatial working memory deficit and disorganization symptoms have been considered significant components of schizophrenic impairment involved with the dorsolateral prefrontal cortex. The purpose of the present study was to investigate the relationships among spatial working memory, psychiatric symptoms including disorganization symptoms, and social functioning in schizophrenia. Fifty clinically stable patients with schizophrenia and 34 healthy controls participated in the study. Patients were rated with the Brief Psychiatric Rating Scale and the Rehabilitation Evaluation Hall and Baker. The Advanced Trail Making Test was used to evaluate spatial working memory. Patients demonstrated significantly reduced spatial working memory compared to that of healthy controls. Spatial working memory in patients correlated significantly with social functioning such as self-care skills, community skills and speech disturbance, and with disorganization symptoms. Disorganization symptoms also correlated with these aspects of social functioning. In conclusion it is suggested that both spatial working memory deficit and disorganization symptoms, which are impairments involved with the dorsolateral prefrontal cortex dysfunction, can serve as effective predictors of social functioning.

The Effects of Clozapine and Risperidone on Spatial Working Memory in Schizophrenia

The purpose of this investigation was to evaluate the effects of clozapine and risperidone on spatial working memory in patients with schizophrenia. Spatial working memory performance was evaluated at baseline and after 17 and 29 weeks in 97 patients with schizophrenia participating in a multisite trial. Compared with baseline performance while receiving conventional antipsychotic medication, risperidone improved, and clozapine worsened, spatial working memory performance. The differential effects of these medications on spatial working memory may be due to the anticholinergic effects of clozapine and prefrontal dopamine-enhancing effects of risperidone.

Effect of switching to atypical antipsychotics on memory in patients with chronic schizophrenia

While the usefulness of atypical antipsychotics for improving cognitive function has been proven, the specific effects of these drugs are still unknown. The objective of this study was to investigate changes of the immediate memory and verbal working memory in patients with chronic schizophrenia after switching to one of four atypical antipsychotic agents and cessation of anticholinergic therapy. The subjects included 77 schizophrenic patients who were treated primarily with typical antipsychotics. Treatment was randomly switched to one of four atypical antipsychotics (olanzapine, perospirone, quetiapine, or risperidone) over a 4-week period, and then the drug was continued for another 4 weeks while the patient was taken off anticholinergics. The immediate memory, verbal working memory, and symptoms were evaluated. Significant improvement of immediate memory was only seen with olanzapine and risperidone. Improvement was also seen after switching to perospirone, but immediate memory worsened after treatment with this anticholinergic drug was discontinued. Deterioration was seen after switching to quetiapine, but immediate memory improved and reached the previous level after treatment with anticholinergic drugs was discontinued. Significant improvement of the verbal working memory was only seen during risperidone administration. The findings suggested that switching chronic schizophrenic patients to atypical antipsychotics can improve both the immediate memory and the verbal working memory when risperidone is used, while improvement of immediate memory can be expected with olanzapine. From the viewpoint of improving the memory, quetiapine should not be administered concomitantly with anticholinergic drugs, and caution should be exercised when discontinuing anticholinergic drugs during treatment with perospirone.

Visual search and visual working memory in patients with chronic focal cortical lesions

Visually guided behavior is known to involve temporo-parietal, inferotemporal, and prefrontal cortex and each of these areas appears to contribute to visual working memory. We explored the extent to which chronic lesions in one of these cortical areas affect visually guided oculomotor performance. We also explore whether possible impairments become more pronounced with increasing memory load. With this aim we recorded saccadic eye movements in 19 patients with a chronic focal postsurgical lesion in either temporo-parietal, inferior temporal or prefrontal cortex. Their results are compared to those of 19 age-matched volunteers. The subjects performed three different visual search tasks with increasing memory load: Instructed search, cue-guided search and memory-guided search. In addition, the latter task was performed with a short (1 s) and a long (6 s) delay. All tasks required the subjects to make a saccade to a single target presented together with one or three distractors. The results indicate that patients with inferotemporal lesions make the most task-related errors. Saccadic reaction times (SRTs) were significantly prolonged in patients with temporo-parietal and prefrontal lesions, but were unaffected in the patients with lesions in the inferotemporal cortex. The spatial accuracy of saccades was lowest in patients with temporo-parietal lesions. An increase in memory load led to more errors, to longer reaction times and to lower saccadic precision. However, the effect was similar across the three patient groups and the controls. An error analysis indicated that both patients and controls tended to weight global (luminance contrast and form) features higher than local features (line-segment orientation) when making difficult perceptual decisions.

Magnesium sulfate therapy affects attention and working memory in patients undergoing preterm labor

Objective: Patients commonly consent to undergoing invasive procedures while receiving magnesium sulfate therapy. This study evaluated the effects of magnesium sulfate on attention, comprehension, and memory in patients undergoing preterm labor. Study Design: Consenting patients were studied while receiving(study) and not receiving (control) intravenous magnesium sulfate tocolysis for preterm labor. Excluded were patients with possible preeclampsia, imminent delivery, sedative administration, or prior mental illness. Patient comprehension was assessed with the Boston Diagnostic Aphasia Examination. Level of attention and working memory were evaluated with the Paced Auditory Serial Addition Test. Verbal learning, short-term memory, and recognition were determined with the Hopkins Verbal Learning Test. Gross mental-neurologic deficits were evaluated with the Mini-Mental Status Examination. The tests were administered by the same examiner. Control testing was performed >24 hours after intravenous magnesium sulfate was discontinued. Magnesium levels were obtained at the time of testing. The primary outcome measure was the Paced Auditory Serial Addition Test score because of its ability to elicit subtle differences in attention capacity. Statistical analysis included the paired t test and the McNemar test. Results: Fifteen patients completed the study. Paced Auditory Serial Addition Test scores were significantly higher (ie, more errors were made) during magnesium sulfate therapy than periods without therapy (14 ± 8 vs 7 ± 7; P < .05). Comprehension (Boston Diagnostic Aphasia Examination score) was not different between the groups ( P = .7). There was no difference in short-term memory (Hopkins Verbal Learning Test) or gross mental-neurologic deficits between the 2 groups (all P > .1). Conclusions: Magnesium sulfate therapy appears to have an effect on attention and working memory but not on long-term memory or comprehension. The significant differences in Paced Auditory Serial Addition Test scores reveal deficits in information-processing ability in patients on a regimen of magnesium sulfate therapy. (Am J Obstet Gynecol 2000;183:940-4.)

Spatial and color working memory in patients with lateral prefrontal cortex lesions

Lateral prefrontal cortex (LPFC) has previously been associated with both attention and working memory. To study both of these mechanisms, patients with LPFC lesions and age-matched controls were tested on working memory tasks that included an interference condition. On a spatial working memory task, patients were impaired overall relative to controls in both no-interference and interference conditions. There was also a significant correlation between patients’ performance and the extent of damage to Area 46. Participants were also tested on a color working memory paradigm, in which they had to remember an object’s color, rather than location. LPFC patients were disproportionately impaired in the interference condition of this experiment—namely, when they had to perform an interference task during the delay period of the color working memory task. These results are discussed with respect to previous animal and human studies of attention and working memory.

Verbal working memory and solvent exposure: a positron emission tomography study.

Neuropsychological studies have documented frontal dysfunction in patients with a history of exposure to organic solvents. The deficits typically observed in these patients appear to be related to working memory (WM). This study used [15O] water positron emission tomography (PET) to examine the pattern of neural activation during verbal working memory in patients with a history of exposure to solvents. Six individuals with solvent exposure were compared with 6 age- and education-matched controls. On the 2 WM tasks examined with PET, with equivalent task performance, participants with solvent exposure demonstrated frontal peaks that were atypical for the tasks, whereas the posterior peaks were typical for the tasks. The results support frontal dysfunction and compensatory use within anterior regions of the WM system in patients with solvent exposure.

Verbal Working Memory Deficit in Parkinson’s Disease Subjects

The aim of the present work was to evaluate verbal working memory in patients affected by Parkinson’s disease (PD). In particular, tests that explore the functionality of the Articulatory Loop and of the Central Executive during verbal tasks were given. PD patients displayed normal phonological similarity, word length and word frequency effects in a Word span task, thus demonstrating adequate retention capacity of the phonological store, normal functioning of the articulatory rehearsal mechanism and a normal contribution of lexical-semantic knowledge to verbal immediate recall. In the Brown-Peterson task, PD patients showed abnormal performance decay on the letter recall task when articulatory rehearsal was inhibited by a serial subtraction concurrent task. These data provide evidence for normal functioning of the Articulatory Loop in PD patients. However, when the verbal recall task is more attention demanding, PD patients show deficient performance levels, presumably due to depleted processing resources by the Central Executive.

Problem-solving and spatial working memory in patients with schizophrenia and with focal frontal and temporal lobe lesions

Problem-solving ability was investigated in 25 DSM-IIIR schizophrenic (SC) patients using the Tower of Hanoi (TOH) task. Their performance was compared to that of: (1) 22 patients with neurosurgical unilateral prefrontal lesions, 11 left (LF) and 10 right hemisphere (RF); (2) 38 patients with unilateral temporal lobectomies, 19 left (LT) and 19 right (RT); and (3) 44 matched control subjects. Like the RT and LF group, the schizophrenics were significantly impaired on the TOH. The deficit shown by the schizophrenic group was equivalent whether or not the problems to be solved included goal–subgoal conflicts, unlike the LF group who were impaired specifically on these problems. The nature of the SC deficit was also distinct from that of the RT group, in that the problem-solving deficit remained after controlling for the effects of spatial memory performance. This study indicates, therefore, that neither focal frontal nor temporal lobe damage sustained in adult life is a sufficient explanation for the problem-solving deficits found in patients with schizophrenia.

Visuospatial working memory in patients with schizophrenia

Recent investigations have documented abnormalities in working memory related processes in schizophrenics on tasks assessing the central executive component of this cognitive model. This preliminary study investigated the function of another component of the working memory system, the visuospatial scratch pad in schizophrenia. The "scratch pad's" passive visual store--responsible for the temporary retention of visual material--was assessed via a computerized spatial delayed response task, whereas its active spatial rehearsal subsystem--specialized for retaining the temporal properties--was explored through visual block span. To assess elemental visual spatial abilities we used the Judgment of Line Orientation test. Thirty-two schizophrenics and 27 controls were tested. Although we discovered the basic perceptual abilities of patients to be intact, we determined that whenever memory was necessitated on spatial tasks, patients demonstrated marked deficits. This pattern of cognitive dysfunction is consistent with impairments in a neural network involving prefrontal and/or posterior brain regions in schizophrenia.

A pen-and-paper human analogue of a monkey prefrontal cortex activation task: spatial working memory in patients with schizophrenia

In order to pursue the hypothesis that the dorsolateral prefrontal cortex is a source of cognitive deficit in schizophrenia, we developed an easily administered pen-and-paper human analogue of a visuospatial working memory task that in non-human primates activates the neurons of Walker area 46 (Goldman-Rakic, 1987). Compared to normal controls, schizophrenic patients made significantly greater errors in identifying where a visuospatial stimulus had been presented to them 30 and 60 seconds earlier, and these differences were significantly greater than in an immediate recall condition. These data suggest that schizophrenic patients have visuospatial working memory deficits that are sensitive to pen-and-paper versions of the tasks that activate the Walker area 46 in non-human primates. The availability of an easily administered test that may be associated with the functioning of the prefrontal cortex may enable more specific assessment of this brain region in humans.

INTERFERENCE FACTORS IN DELAYED RESPONSE IN MONKEYS AFTER REMOVAL OF FRONTAL LOBES

INTERFERENCE FACTORS IN DELAYED RESPONSE IN MONKEYS AFTER REMOVAL OF FRONTAL LOBES