Decreased activation of anterior cingulate cortex in the working memory of the elderly

We examined aging effects on activation in the anterior cingulate cortex during a verbal working memory using functional magnetic resonance imaging. Ten young (mean age 25 years) and 10 elderly (mean age 69 years) healthy adults performed the reading span test in which performance reflects individual differences in verbal working memory. We found an age-related difference in executive function in the prefrontal cortex; younger participants showed significant anterior cingulate cortex activation whereas the elderly did not. We found that the anterior cingulate cortex plays a critical role in executive function related to working memory. We found that behavioral deficits in verbal working memory because of aging result from the deterioration of cognitive control owing to decreased activation of the anterior cingulate cortex.     

A systematic fMRI investigation of the brain systems subserving different working memory components in schizophrenia

Working memory impairment is one of the cardinal cognitive disturbances in schizophrenia and considerable evidence suggests that it can be traced to functional alterations in the brain. The exact allocation of specific deficits to regional specific dysfunctions, however, remains elusive. The aim of this study was to examine the functional integrity of three distinguishable brain systems underlying maintenance-related subprocesses of working memory (articulatory rehearsal, non-articulatory maintenance of phonological information, maintenance of visuospatial information) in patients with schizophrenia. Using an experimental paradigm, which had been designed to selectively activate these different brain systems, we assessed the brain activation of patients and controls with functional magnetic resonance imaging. Compared with controls, patients showed reduced activation of the fronto-opercular, intraparietal and anterior cingulate cortex during the non-articulatory maintenance of phonological information, as well as attenuated deactivation of the hippocampus. Additionally, we found prefrontal activation to depend critically on the patients' current symptom status. During visuospatial maintenance, patients showed impaired activation of the superior parietal, temporal and occipital cortex, combined with enhanced activation of the frontal eye field and the inferior parietal cortex. No abnormal activations were observed during the articulatory rehearsal task. All activation differences were independent of group differences in task performance. Our fine-grained analysis of dysfunctions in particular aspects of working memory circuitry provides evidence for a differential impairment of the brain systems supporting working memory subcomponents in schizophrenia and extends knowledge of the relationship between cognitive deficits, brain activation abnormalities and symptoms in schizophrenia.     

Event-related fMRI of frontotemporal activity during word encoding and recognition in schizophrenia

OBJECTIVE: Neuropsychological studies have demonstrated verbal episodic memory deficits in schizophrenia during word encoding and retrieval. This study examined neural substrates of memory in an analysis that controlled for successful retrieval. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation during word encoding and recognition in 14 patients with schizophrenia and 15 healthy comparison subjects. An unbiased multiple linear regression procedure was used to model the BOLD response, and task effects were detected by contrasting the signal before and after stimulus onset. RESULTS: Patients attended during encoding and had unimpaired reaction times and normal response biases during recognition, but they had lower recognition discriminability scores, compared with the healthy subjects. Analysis of contrasts was restricted to correct items. Previous findings of a deficit in bilateral prefrontal cortex activation during encoding in patients were reproduced, but patients showed greater parahippocampal activation rather than deficits in temporal lobe activation. During recognition, left dorsolateral prefrontal cortex activation was lower in the patients and right anterior prefrontal cortex activation was preserved, as in the authors' previous study using positron emission tomography. Successful retrieval was associated with greater right dorsolateral prefrontal cortex activation in the comparison subjects, whereas orbitofrontal, superior frontal, mesial temporal, middle temporal, and inferior parietal regions were more active in the patients during successful retrieval. CONCLUSIONS: The pattern of prefrontal cortex underactivation and parahippocampal overactivation in the patients suggests that functional connectivity of dorsolateral prefrontal and temporal-limbic structures is disrupted by schizophrenia. This disruption may be reflected in the memory strategies of patients with schizophrenia, which include reliance on rote rehearsal rather than associative semantic processing.     

fMRI study of maintenance and manipulation processes within working memory in first-episode schizophrenia

OBJECTIVE: Working memory, a critical cognitive capacity that is affected in schizophrenia, can be divided into maintenance and manipulation processes. Previous behavioral research suggested that manipulation is more affected than maintenance in patients with chronic schizophrenia. In this study of first-episode schizophrenia patients, the authors evaluated the extent to which the two working memory processes are affected early in the course of schizophrenia. METHOD: Study subjects were 11 first-episode schizophrenia patients and 11 matched healthy comparison subjects. Each group performed two verbal working memory tasks while undergoing functional magnetic resonance imaging. One task required maintenance of information; the other required manipulation of information in addition to maintenance. RESULTS: Under behaviorally matched conditions, both groups activated a predominantly left-sided frontal-parietal network. The manipulation plus maintenance task elicited activation of greater magnitude and spatial extent. With both tasks, patients showed less bilateral dorsolateral prefrontal cortex activation and greater ventrolateral prefrontal cortex activation, relative to the comparison subjects. A group-by-task interaction was observed for activation at the left dorsolateral and ventrolateral prefrontal cortex. The increase in activation when patients engaged in the manipulation plus maintenance task was disproportionately less in the dorsolateral prefrontal cortex and greater in the ventrolateral prefrontal cortex. CONCLUSIONS: These functional neuroanatomical findings add support to earlier suggestions that manipulation of information is selectively more affected than maintenance of information in persons with schizophrenia. They also suggest the presence of interacting regions of dysfunctional and compensatory prefrontal responses in the dorsolateral and ventrolateral prefrontal cortex, respectively, that are more prominent when information is manipulated. This disrupted prefrontal network is present relatively early in the course of schizophrenia.     

Neocortical system abnormalities in autism: an fMRI study of spatial working memory

OBJECTIVE: To test the hypothesis that deficits in spatial working memory in autism are due to abnormalities in prefrontal circuitry. METHODS: Functional MRI (fMRI) at 3 T was performed in 11 rigorously diagnosed non-mentally retarded autistic and six healthy volunteers while they performed an oculomotor spatial working memory task and a visually guided saccade task. RESULTS: Autistic subjects demonstrated significantly less task-related activation in dorsolateral prefrontal cortex (Brodmann area [BA] 9/46) and posterior cingulate cortex (BA 23) in comparison with healthy subjects during a spatial working memory task. In contrast, activation of autistic individuals was not reduced in other regions comprising the neural circuitry for spatial working memory including the cortical eye fields, anterior cingulate cortex, insula, basal ganglia, thalamus, and lateral cerebellum. Autistic subjects also did not demonstrate reduced activation in any brain regions while performing visually guided saccades. CONCLUSION: Impairments in executive cognitive processes in autism may be subserved by abnormalities in neocortical circuitry as evidenced by decreased activation in prefrontal and posterior cingulate circuitry during a spatial working memory task.     

An FMRI study of episodic encoding and recognition of words in patients with schizophrenia in remission

OBJECTIVE: Verbal memory deficits are among the most severe cognitive deficits observed in patients with schizophrenia. This study examined patterns of brain activity during episodic encoding and recognition of words in patients with schizophrenia. METHOD: Functional magnetic resonance imaging (fMRI) was used to study regional brain activation in 10 healthy male comparison subjects and 10 male outpatients with schizophrenia during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite having intact performance in word recognition, the patients with schizophrenia had less activation of the right dorsolateral and anterior prefrontal cortex, right anterior cingulate, and left lateral temporal cortex during word encoding, compared with the healthy comparison subjects. During word recognition, the patients had impairments in activation of the bilateral dorsolateral prefrontal and lateral temporal cortices. CONCLUSIONS: Schizophrenia was associated with attenuated frontotemporal activation during episodic encoding and recognition of words. These results from an fMRI study replicate earlier findings derived from a positron emission tomography study.     

Dysfunctional prefrontal regional specialization and compensation in schizophrenia

OBJECTIVE: It has been suggested that in healthy persons higher-order cognitive processing engaged by incremental working memory load hierarchically employs more dorsal than ventral prefrontal resources in healthy individuals. Given that working memory performance is impaired in schizophrenia, especially at higher executive loads, the authors investigated how this prefrontal functional organization might be altered in disease, independent of performance deficits. METHOD: Using N-back working memory functional magnetic resonance imaging (fMRI) data, the authors studied 15 patients with schizophrenia and 26 healthy comparison subjects. Subgroups based on median performance accuracy at 2-back were analyzed; high performers included eight schizophrenia patients and 14 comparison subjects, and low performers included seven patients and 12 comparison subjects. RESULTS: High-performing but not low-performing comparison subjects responded to incremental working memory executive load with disproportionately greater dorsal but not ventral prefrontal cortex activation, which also predicted performance accuracy. In the high- and low-performing patient groups, incremental working memory load caused a disproportionate increase in ventral but not dorsal prefrontal cortex activation relative to the respective comparison group, which also correlated with accuracy. Functional connectivity between the ventral prefrontal cortex and posterior parietal cortex was relatively greater in patients, whereas comparison subjects had greater functional connectivity between the dorsal prefrontal cortex and posterior parietal cortex. CONCLUSIONS: The hierarchical organization of the prefrontal cortex may be compromised in schizophrenia, resulting in loss of functional specialization and integration at the dorsal prefrontal cortex and in compensatory activation from the ventral prefrontal cortex, which may ultimately affect working memory and executive cognition.     

Functional magnetic resonance imaging during auditory verbal working memory in nonpsychotic relatives of persons with schizophrenia: a pilot study.

BACKGROUND: First-degree relatives of persons with schizophrenia carry elevated genetic risk for the illness and show deficits on high-load information processing tasks. We used functional magnetic resonance imaging (fMRI) to test whether nonpsychotic relatives show altered functional activation in the prefrontal cortex (PFC), thalamus, hippocampus, and anterior cingulate during a working memory task requiring interference resolution. METHODS: Twelve nonpsychotic relatives of persons with schizophrenia and 12 healthy control subjects were administered an auditory, verbal working memory version of the Continuous Performance Test during fMRI. An asymmetric, spin-echo, T2*-weighted sequence (15 contiguous, 7-mm axial slices) was acquired on a full-body MR scanner. Data were analyzed by Statistical Parametric Mapping (SPM). RESULTS: Compared with control subjects, relatives showed greater task-elicited activation in the PFC and the anterior and dorsomedial thalamus. When task performance was controlled, relatives showed significantly greater activation in the anterior cingulate. When effects of other potentially confounding variables were controlled, relatives generally showed significantly greater activation in the dorsomedial thalamus and anterior cingulate. CONCLUSIONS: This pilot study suggests that relatives of persons with schizophrenia have subtle differences in brain function in the absence of psychosis. These differences add to the growing literature identifying neurobiological vulnerabilities to schizophrenia.     

Impact of emotional salience on episodic memory in attention-deficit/hyperactivity disorder: a functional magnetic resonance imaging study.

BACKGROUND: Patients with attention-deficit/hyperactivity disorder (ADHD) show episodic memory deficits especially in complex memory tasks. We investigated the neural correlates of memory formation in ADHD and their modulation by stimulus salience. METHODS: We recorded event-related functional magnetic resonance imaging during an episodic memory paradigm with neutral and emotional pictures in 12 male ADHD subjects and 12 healthy adolescents. RESULTS: Emotional salience did significantly augment memory performance in ADHD patients. Successful encoding of neutral pictures was associated with activation of the anterior cingulate cortex (ACC) in healthy adolescents but with activation of the superior parietal lobe (SPL) and precuneus in ADHD patients. Successful encoding of emotional pictures was associated with prefrontal and inferior temporal cortex activation in both groups. Healthy adolescents, moreover, showed deactivation in the inferior parietal lobe. CONCLUSIONS: From a pathophysiological point of view, the most striking functional differences between healthy adolescents and ADHD patients were in the ACC and SPL. We suggest that increased SPL activation in ADHD reflected attentional compensation for low ACC activation during the encoding of neutral pictures. The higher salience of emotional stimuli, in contrast, regulated the interplay between ACC and SPL in conjunction with improving memory to the level of healthy adolescents.     

Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression.

BACKGROUND: A large number of studies suggest the presence of deficits in dorsolateral prefrontal cortex function during performance of working memory tasks in individuals with schizophrenia. However, working memory deficits may also present in other psychiatric disorders, such as major depression. It is not clear whether people with major depression also demonstrate impaired prefrontal activation during performance of working memory tasks. METHODS: We used functional magnetic resonance imaging to assess the patterns of cortical activation associated with the performance of a 2-back version of the N-Back task (working memory) in 38 individuals with schizophrenia and 14 with major depression. RESULTS: We found significant group differences in the activation of dorsolateral prefrontal cortex associated with working memory performance. Consistent with prior research, participants with schizophrenia failed to show activation of right dorsolateral prefrontal cortex in response to working memory tasks demands, whereas those with major depression showed clear activation of right and left dorsolateral prefrontal cortex as well as bilateral activation of inferior and superior frontal cortex. CONCLUSIONS: During performance of working memory tasks, deficits in prefrontal activation, including dorsolateral regions, are more severe in participants with schizophrenia (most of whom were recently released outpatients) than in unmedicated outpatients with acute nonpsychotic major depression.     

Load-related brain activation predicts spatial working memory performance in youth aged 9–12 and is associated with executive function at earlier ages

Spatial working memory is a central cognitive process that matures through adolescence in conjunction with major changes in brain function and anatomy. Here we focused on late childhood and early adolescence to more closely examine the neural correlates of performance variability during this important transition period. Using a modified spatial 1-back task with two memory load conditions in an fMRI study, we examined the relationship between load-dependent neural responses and task performance in a sample of 39 youth aged 9–12 years. Our data revealed that between-subject differences in task performance was predicted by load-dependent deactivation in default network regions, including the ventral anterior cingulate cortex (vACC) and posterior cingulate cortex (PCC). Although load-dependent increases in activation in prefrontal and posterior parietal regions were only weakly correlated with performance, increased prefrontal–parietal coupling was associated with better performance. Furthermore, behavioral measures of executive function from as early as age 3 predicted current load-dependent deactivation in vACC and PCC. These findings suggest that both task positive and task negative brain activation during spatial working memory contributed to successful task performance in late childhood/early adolescence. This may serve as a good model for studying executive control deficits in developmental disorders.     

Dorsolateral prefrontal cortex activity during maintenance and manipulation of information in working memory in patients with schizophrenia

CONTEXT: It remains unclear whether altered regional brain physiological activity in patients with schizophrenia during working memory tasks relates to maintenance-related processes, manipulation-related (ie, executive) processes, or both. OBJECTIVE: To examine regional functional activations of the brain during maintenance- and manipulation-related working memory processing in patients with schizophrenia and in healthy comparison subjects. DESIGN: Functional images of the brain were acquired in 11 schizophrenic patients and 12 healthy control subjects (matched for age, sex, handedness, and parental education) during 2 spatial working memory paradigms, one contrasting maintenance-only processing with maintenance and manipulation processing and the other contrasting parametrically varying maintenance demands. RESULTS: Patients and controls showed activation of a large, spatially distributed network of cortical and subcortical regions during spatial working memory processing. When task demands required explicit manipulation of information held in memory, controls recruited right dorsolateral prefrontal cortex (Brodmann areas 45 and 46) to a significantly greater extent than patients. A similar effect was observed for the larger memory set sizes of the memory set size task. No other brain regions showed activation differences between groups for either task. These differences persisted when comparing activation maps for memory set sizes in which the 2 groups were equivalent in behavioral accuracy and when comparing subgroups of patients and controls matched for behavioral accuracy on either task. CONCLUSIONS: Physiological disturbances in the dorsolateral prefrontal cortex contribute differentially to patients' difficulties with maintaining spatial information across a brief delay, as well as with manipulating the maintained representation. These differences persisted when comparing conditions in which the 2 groups were equivalent in behavioral accuracy.     

The neural basis of relational memory deficits in schizophrenia

CONTEXT: Memory deficits are common in schizophrenia. Recent studies have demonstrated that relational memory is particularly impaired. OBJECTIVE: To study the neural correlates of relational memory in schizophrenia using functional magnetic resonance imaging. DESIGN: Cross-sectional case-control study. SETTING: Academic medical center.Subjects Twenty patients with schizophrenia and 17 control subjects. MAIN OUTCOME MEASURES: Behavioral performance and brain activity were assessed during the discrimination of previously seen and novel pairs of visual stimuli, which varied in the degree of relational memory load. We performed whole-brain and region-of-interest (hippocampus) analyses. RESULTS: Schizophrenic subjects displayed normal activation of the presupplementary motor area and ventral prefrontal cortex, but significantly decreased recruitment of the right parietal cortex and anterior cingulate cortex when discriminating novel pairs derived from a sequence of stimuli. Discrimination accuracy was decreased in schizophrenia only when the flexible representation of a sequence was required. This selective deficit was associated with decreased activation of the right parietal cortex and left hippocampus. CONCLUSIONS: Schizophrenia is characterized by a specific deficit of relational memory, which is associated with impaired function of the parietal cortex and hippocampus. Abnormal relational memory may be at the core of 2 prominent features of schizophrenia, ie, cognitive deficits and psychosis.     

Abnormal parietal cortex activation during working memory in schizophrenia: verbal phonological coding disturbances versus domain-general executive dysfunction

OBJECTIVE: The goal of this study was to determine whether the regions of the prefrontal and parietal cortices showing abnormal activation among individuals with schizophrenia during working memory tasks are associated with either 1) phonological coding processes that may be specific to verbal tasks (i.e., ventral prefrontal and parietal cortices) or 2) domain-general executive processes engaged by verbal and nonverbal tasks (i.e., dorsal prefrontal and parietal cortices). METHOD: The participants were 57 medicated individuals with schizophrenia and 120 healthy subjects. Functional magnetic resonance imaging was used to scan all participants during performance of verbal and nonverbal 2-back working memory tasks. RESULTS: In the healthy subjects there was similar bilateral dorsal prefrontal and inferior parietal cortex activation for both the verbal and nonverbal working memory tasks, but greater left ventral prefrontal and parietal cortex activation during verbal compared to nonverbal working memory. Individuals with schizophrenia showed bilateral deficits in dorsal frontal and parietal activation during both verbal and nonverbal working memory tasks. They also demonstrated the typical pattern of greater activity for verbal, as compared to nonverbal, working memory in ventral prefrontal and parietal regions, although they showed less verbal superiority in a left ventral prefrontal region. CONCLUSIONS: These results support the hypothesis that working memory deficits in individuals with schizophrenia reflect deficits in activation of brain regions associated with the central executive components of working memory rather than domain-specific storage buffers.     

Neural correlates of working memory performance in adolescents and young adults with dyslexia

Behavioral studies indicate deficits in phonological working memory (WM) and executive functioning in dyslexics. However, little is known about the underlying functional neuroanatomy. In the present study, neural correlates of WM in adolescents and young adults with dyslexia were investigated using event-related functional magnetic resonance imaging (fMRI) and a parametric verbal WM task which required the manipulation of verbal material. Dyslexics were not significantly slower than controls; however, they were less accurate with the highest WM demand. The functional analysis excluded incorrectly performed and omitted trials, thus controlling for potential activation confounds. Compared with control subjects, both increased and decreased activation of the prefrontal cortex were found in the dyslexic group. Dyslexics showed significantly more activation than controls with increasing WM demand in the left superior frontal gyrus (BA 8), as well as in the inferior frontal gyrus including Broca's area (BA 44) and its right homologue. Less activation was found in the middle frontal gyrus (BA 6) and in the superior parietal cortex (BA 7). A positive correlation between activation of prefrontal regions and verbal WM performance (as measured by digit span backwards) was found only in the dyslexic group. Accuracy deficits at the highest cognitive demand during the verbal WM task and the digit span backwards suggest that manipulation rather than maintenance is selectively impaired in dyslexics. The fMRI data provide further evidence for functional differences in cortical regions associated with language processing and executive function in subjects with dyslexia.     

Lateral and medial hypofrontality in first-episode schizophrenia: functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment

OBJECTIVE: The dorsolateral prefrontal cortex and the anterior cingulate cortex are critical components of the brain circuitry underlying executive control. The objective of this study was to investigate control-related dorsolateral prefrontal cortex functioning and conflict-related anterior cingulate cortex functioning in a group of never medicated first-episode schizophrenia patients to determine whether both regions show dysfunction at illness onset. A second objective was to assess short-term effects of atypical antipsychotic medication on dorsolateral prefrontal cortex and anterior cingulate cortex functioning. METHOD: First-episode schizophrenia patients (N=23) and healthy comparison subjects (N=24) underwent event-related fMRI and performed a cognitive task designed to functionally dissociate the two regions. Four weeks after initiation of pharmacotherapy for patients, a subset of 11 patients and 16 comparison subjects underwent a repeat assessment. RESULTS: At baseline, patients exhibited hypoactivation in the dorsolateral prefrontal cortex and anterior cingulate cortex. After 4 weeks of antipsychotic treatment, the patients demonstrated improved functioning in the anterior cingulate cortex but not in the dorsolateral prefrontal cortex. CONCLUSIONS: These findings confirm the presence of dorsolateral prefrontal cortex dysfunction early in the course of schizophrenia and suggest that anterior cingulate cortex functioning may be altered at illness onset as well. Results also suggest that anterior cingulate cortex functioning may be especially sensitive to remedial antipsychotic treatment effects. These findings are consistent with an emerging literature documenting short-term benefits of atypical antipsychotic medication for the neural circuitry underlying cognitive deficits in schizophrenia.     

Functional magnetic resonance imaging studies of eye movements in first episode schizophrenia: smooth pursuit, visually guided saccades and the oculomotor delayed response task

Schizophrenia patients show eye movement abnormalities that suggest dysfunction in neocortical control of the oculomotor system. Fifteen never-medicated, first episode schizophrenia patients and 24 matched healthy individuals performed eye movement tasks during functional magnetic resonance imaging studies. For both visually guided saccade and smooth pursuit paradigms, schizophrenia patients demonstrated reduced activation in sensorimotor areas supporting eye movement control, including the frontal eye fields, supplementary eye fields, and parietal and cingulate cortex. The same findings were observed for an oculomotor delayed response paradigm used to assess spatial working memory, during which schizophrenia patients also had reduced activity in dorsolateral prefrontal cortex. In contrast, only minimal group differences in activation were found during a manual motor task. These results suggest a system-level dysfunction of cortical sensorimotor regions supporting oculomotor function, as well as in areas of dorsolateral prefrontal cortex that support spatial working memory. These findings indicate that a generalized rather than localized pattern of neocortical dysfunction is present early in the course of schizophrenia and is related to deficits in the sensorimotor and cognitive control of eye movement activity.     

Effect of schizophrenia on frontotemporal activity during word encoding and recognition: a PET cerebral blood flow study.

OBJECTIVE: Neuropsychological studies have shown that deficits in verbal episodic memory in schizophrenia occur primarily during encoding and retrieval stages of information processing. The current study used positron emission tomography to examine the effect of schizophrenia on change in cerebral blood flow (CBF) during these memory stages. METHOD: CBF was measured in 23 healthy comparison subjects and 23 patients with schizophrenia during four conditions: resting baseline, motor baseline, word encoding, and word recognition. The motor baseline was used as a reference that was subtracted from encoding and recognition conditions by using statistical parametric mapping. RESULTS: Patients' performance was similar to that of healthy comparison subjects. During word encoding, patients showed reduced activation of left prefrontal and superior temporal regions. Reduced left prefrontal activation in patients was also seen during word recognition, and additional differences were found in the left anterior cingulate, left mesial temporal lobe, and right thalamus. Although patients' performance was similar to that of healthy comparison subjects, left inferior prefrontal activation was associated with better performance only in the comparison subjects. CONCLUSIONS: Left frontotemporal activation during episodic encoding and retrieval, which is associated with better recognition in healthy people, is disrupted in schizophrenia despite relatively intact recognition performance and right prefrontal function. This may reflect impaired strategic use of semantic information to organize encoding and facilitate retrieval.     

Working memory functioning in schizophrenia patients and their first-degree relatives: cognitive functioning shedding light on etiology

There is accumulating evidence for involvement of the prefrontal cortex (PFC) in the pathophysiology of schizophrenia. A primary function supported by the PFC is working memory (WM). Findings from WM studies in schizophrenia can provide insight into the nature of clinical symptoms and cognitive deficits associated with this disorder, as well as begin to suggest areas of underlying neuropathology. To date, studies have not adequately investigated different WM domains (e.g., verbal, spatial, or object) or processing requirements (e.g., maintenance, monitoring, or manipulation), shown to be associated with distinct patterns of neural activation, in schizophrenia patients and their well relatives. Accordingly, this study evaluated the performance of schizophrenia patients, their first-degree biological relatives, and nonpsychiatric controls on a comprehensive battery of WM tasks and investigated the association among WM deficits and schizophrenia-spectrum psychopathology. The findings indicate that schizophrenia patients are consistently impaired on WM tasks, irrespective of WM domain or processing requirements. In contrast, their unaffected relatives are only impaired on WM tasks with higher central executive processing requirements. This pattern of WM performance may further implicate DLPFC dysfunction in the liability for schizophrenia and has implications for future cognitive, genetic, and neurodevelopmental research.     

Working memory in schizophrenia: a review

INTRODUCTION: Working memory refers to a limited capacity system for temporary storage and processing of information that is known to depend on the integrity of the prefrontal cortex. It has been classically described as composed of a "central executive" that performs control, selection and planning functions, and two "slave" systems: on the one hand, the phonological loop that holds verbal, speech-based representations, and on the other hand, the visuospatial sketchpad that manipulates spatial and object visual representations. LITERATURE FINDINGS: Studies in schizophrenia have used different tasks that tap different processes within the working memory. Despite the variety of measures, there is solid neuropsychological evidence that patients with schizophrenia demonstrate deficits in all subsystems of working memory. Several studies have shown no correlations between working memory deficits and age, gender, premorbid IQ, duration of disease or positive syndrome, but a correlation has been found with a low-educational level, and negative and disorganization symptoms. Neuroimaging studies have provided evidence of an involvement of the dorsolateral-prefrontal cortex during working memory performance. Many studies have demonstrated a functional deficit in this area. However, several recent studies have reported either equal or increased activation of the dorsolateral-prefrontal cortex in schizophrenia during working memory performance. Working memory deficits are present early in the course of schizophrenia and they have been shown to be consistently associated with reduced levels of elementary social skills and learning capacity. Unaffected relatives of individuals with schizophrenia and individuals diagnosed with schizotypal personality demonstrate deficits in tasks designed to measure working memory function. Working memory dysfunctions might be suitable candidate markers for vulnerability. Certain executive sub-processes seem to be the most heritable component of the working memory. Working memory deficits in schizophrenia may benefit from specific stimulation of receptors such as the dopaminergic D1 receptor, adrenergic alpha-2A receptor or nicotinic receptors. Few studies on the effect of antipsychotic medication on working memory in schizophrenia have been carried out and their results are highly variable. Atypical antipsychotic drugs, notably risperidone, have appeared to improve performance in working memory tasks. Cognitive exercises can improve working memory with a six-month persistent effect.