Disturbed functional connectivity within brain networks subserving domain-specific subcomponents of working memory in schizophrenia: Relation to performance and clinical symptoms

Introduction

Disturbed interregional functional connectivity has been hypothesized to be a promising marker of schizophrenia. The relationship between working memory (WM) impairment, disturbed functional connectivity, and the characteristic symptoms of schizophrenia, however, remains elusive.

Methods

We used functional MRI (fMRI) to investigate in patients with schizophrenia and matched controls the patterns of functional connectivity during the performance of different tasks selectively engaging subcomponent processes of working memory.

Results

Compared with controls, patients showed reduced connectivity of the prefrontal cortex with the intraparietal cortex and the hippocampus and abnormal negative interactions between the ventrolateral and dorsolateral prefrontal cortex during the non-articulatory maintenance of phonological information. During the maintenance of visuospatial information, patients presented reduced connectivity between regions in the superior parietal and occipital cortex, as well as enhanced positive connectivity of the frontal eye field with visual processing areas.

Discussion

Our findings suggest complex dysregulations within the networks supporting working memory functions in schizophrenia, which manifest as decreased positive and abnormal negative interactions. Correlations between the connection strength and WM performance suggest that these dysregulations may be neurofunctional correlates of the WM deficits seen in schizophrenia. Altered prefronto-hippocampal and parieto-occipital connectivity was further found to be associated with higher positive symptoms, providing a possible explanation for the development of delusions and disorganization symptoms.

Conclusion

The present findings can help to better understand the relationship between altered patterns of synchronized brain activity and the cognitive and clinical symptoms of schizophrenia.     

Dynamic interactions between neural systems underlying different components of verbal working memory

Summary Brain functions are determined not only by processing in single brain areas but also by dynamic interactions within and between distributed neural networks. We investigated functional connectivity between two brain systems underlying complementary components of verbal working memory. The use of the articulatory rehearsal (“inner speech”) mechanism enhanced neural activity in ventral premotor cortex and Broca’s area. These activations showed a negative functional coupling with anatomically connected brain regions subserving the non-articulatory maintenance of phonological information, i.e. the “inner ear”.     

Diagnosis-specific effect of familial loading on verbal working memory in schizophrenia

Background  Working memory disturbances are a frequently replicated finding in schizophrenia and less consistent also in schizoaffective disorder. Working memory dysfunctions have been shown to be heritable and have been proposed to represent a promising endophenotype of schizophrenic psychoses. Methods   In the present study, we investigated the effects of familial loading on performance rates in circuit-specific verbal and visuospatial working memory tasks in matched samples of schizophrenic patients (from multiply affected or uniaffected families), schizoaffective patients (from multiply affected or uniaffected families), and healthy subjects. Results  We found a significant interaction effect between familial loading and diagnosis in terms of a diagnosis-specific detrimental effect of familial loading on the performance of schizophrenic (but not schizoaffective) patients in the articulatory rehearsal task. Conclusion  This finding of a circuit-specific verbal working memory deficit in schizophrenic patients with additional familial loading is consistent with prior studies, which provided evidence for the existence of specific subgroups of schizophrenic patients with selective working memory impairments and for diagnosis-specific dysfunctions of the articulatory rehearsal mechanism in schizophrenic, but not in schizoaffective patients. Together, these findings suggest that the genetic risk for (a subtype of) schizophrenia may be associated with dysfunctions of the brain system, which underlies the articulatory rehearsal mechanism, the probably phylogenetically youngest part of human working memory.     

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.     

Patients with schizophrenia show deficits of working memory maintenance components in circuit-specific tasks

Working memory (WM) deficits are a neuropsychological core finding in patients with schizophrenia and also supposed to be a potential endophenotype of schizophrenia. Yet, there is a large heterogeneity between different WM tasks which is partly due to the lack of process specificity of the tasks applied. Therefore, we investigated WM functioning in patients with schizophrenia using process- and circuit-specific tasks. Thirty-one patients with schizophrenia and 47 controls were tested with respect to different aspects of verbal and visuospatial working memory using modified Sternberg paradigms in a computer-based behavioural experiment. Total group analysis revealed significant impairment of patients with schizophrenia in each of the tested WM components. Furthermore, we were able to identify subgroups of patients showing different patterns of selective deficits. Patients with schizophrenia exhibit specific and, in part, selective WM deficits with indirect but conclusive evidence of dysfunctions of the underlying neural networks. These deficits are present in tasks requiring only maintenance of verbal or visuospatial information. In contrast to a seemingly global working memory deficit, individual analysis revealed differential patterns of working memory impairments in patients with schizophrenia.     

A systematic experimental neuropsychological investigation of the functional integrity of working memory circuits in major depression

Verbal and visuospatial working memory (WM) impairment is a well-documented finding in psychiatric patients suffering from major psychoses such as schizophrenia or bipolar affective disorder. However, in major depression (MDD) the literature on the presence and the extent of WM deficits is inconsistent. The use of a multitude of different WM tasks most of which lack process-specificity may have contributed to these inconsistencies. Eighteen MDD patients and 18 healthy controls matched with regard to age, gender and education were tested using process- and circuit-specific WM tasks for which clear brain-behaviour relationships had been established in prior functional neuroimaging studies. Patients suffering from acute MDD showed a selective impairment in articulatory rehearsal of verbal information in working memory. By contrast, visuospatial WM was unimpaired in this sample. There were no significant correlations between symptom severity and WM performance. These data indicate a dysfunction of a specific verbal WM system in acutely ill patients with MDD. As the observed functional deficit did not correlate with different symptom scores, further, longitudinal studies are required to clarify whether and how this deficit is related to illness acuity and clinical state of MDD patients.     

Disrupted functional connectivity for controlled visual processing as a basis for impaired spatial working memory in schizophrenia

Although regional brain abnormalities underlying spatial working memory (SWM) deficits in schizophrenia have been identified, little is known about which brain circuits are functionally disrupted in the SWM network in schizophrenia. We investigated SWM-related interregional functional connectivity in schizophrenia using functional magnetic resonance imaging (fMRI) data collected during a memory task that required analysis of spatial information in object structure. Twelve schizophrenia patients and 11 normal control subjects participated. Patients had SWM performance deficits and deficient neural activation in various brain areas, especially in the high SWM load condition. Examination of the covariation of regional brain activations elicited by the SWM task revealed evidence of functional disconnection between prefrontal and posterior visual association areas in schizophrenia. Under low SMW load, we found reduced functional associations between dorsolateral prefrontal cortex (DLPFC) and inferior temporal cortex (ITC) in the right hemisphere in patients. Under high SWM load, we found evidence for further functional disconnection in patients, including additional reduced functional associations between left DLPFC and right visual areas, including the posterior parietal cortex (PPC), fusiform gyrus, and V1, as well as between right inferior frontal cortex and right PPC. Greater prefrontal-posterior cortical functional connectivity was associated with better SWM performance in controls, but not in patients. These results suggest that prefrontal-posterior functional connectivity associated with the maintenance and control of visual information is central to SWM, and that disruption of this functional network underlies SWM deficits in schizophrenia.     

Visuospatial working memory in children and adolescents with 22q11.2 deletion syndrome; an fMRI study

22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with a microdeletion of chromosome 22q11. In addition to high rates of neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder, children with 22q11DS have a specific neuropsychological profile with particular deficits in visuospatial and working memory. However, the neurobiological substrate underlying these deficits is poorly understood. We investigated brain function during a visuospatial working memory (SWM) task in eight children with 22q11DS and 13 healthy controls, using fMRI. Both groups showed task-related activation in dorsolateral prefrontal cortex (DLPFC) and bilateral parietal association cortices. Controls activated parietal and occipital regions significantly more than those with 22q11DS but there was no significant between-group difference in DLPFC. In addition, while controls had a significant age-related increase in the activation of posterior brain regions and an age-related decrease in anterior regions, the 22q11DS children showed the opposite pattern. Genetically determined differences in the development of specific brain systems may underpin the cognitive deficits in 22q11DS, and may contribute to the later development of neuropsychiatric disorders.     

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.     

Pathological amygdala activation during working memory performance: Evidence for a pathophysiological trait marker in bipolar affective disorder

Recent evidence suggests that deficits of working memory may be a promising neurocognitive endophenotype of bipolar affective disorder. However, little is known about the neurobiological correlates of these deficits. The aim of this study was to determine possible pathophysiological trait markers of bipolar disorder in neural circuits involved in working memory. Functional magnetic resonance imaging was performed in 18 euthymic bipolar patients and 18 matched healthy volunteers using two circuit‐specific experimental tasks established by prior systematic neuroimaging studies of working memory. Both euthymic bipolar patients and healthy controls showed working memory‐related brain activations that were highly consistent with findings from previous comparable neuroimaging studies in healthy subjects. While these patterns of brain activation were completely preserved in the bipolar patients, only the patients exhibited activation of the right amygdala during the articulatory rehearsal task. In the same task, functional activation in right frontal and intraparietal cortex and in the right cerebellum was significantly enhanced in the patients. These findings indicate that the right amygdala is pathologically activated in euthymic bipolar patients during performance of a circuit‐specific working memory task (articulatory rehearsal). This pathophysiological abnormality appears to be a trait marker in bipolar disorders that can be observed even in the euthymic state and that seems to be largely independent of task performance and medication. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

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.     

Inefficient executive cognitive control in schizophrenia is preceded by altered functional activation during information encoding: an fMRI study

Working memory deficits are a core feature of schizophrenia. Previous working memory studies suggest a load dependent storage deficit. However, explicit studies of higher executive working memory processes are limited. Moreover, few studies have examined whether subcomponents of working memory such as encoding and maintenance of information are differentially affected by these deficits. Therefore, the aim of the present study was to examine the neural substrates of working memory subprocesses requiring stimulus encoding, maintenance and higher executive processing. Using functional magnetic resonance imaging a modified Sternberg working memory task involving verbal stimulus material was applied. The event-related design enabled the segregation of encoding, active maintenance and executive manipulation of information. Forty-one patients with schizophrenia and 41 healthy subjects were included. Relative to normal controls, schizophrenic patients demonstrated a significantly stronger activation pattern in a fronto-parietal network during executive information manipulation. Additionally, significant relative hypoactivity was detectable in the thalamus. Conversely, during stimulus encoding the patients demonstrated lower activation relative to controls in the prefrontal cortex and the anterior cingulate gyrus. The present findings indicate a pronounced prefrontal functional hyperactivation within the neural network subserving higher executive working memory control processes in schizophrenia. Moreover, they suggest that these altered activations during executive control are related to a preceding abnormality of information encoding. During encoding, a reduced activation in mainly dorsolateral prefrontal and anterior cingulate regions was observed. These results could be explained by increased top-down control processing from prefrontal cortex as a compensation for functional deficits occurring during encoding.     

Shared and distinct neurophysiological components of the digits forward and backward tasks as revealed by functional neuroimaging

The digits forward (DF) and backward (DB) tasks are widely used neuropsychological measures believed to tap overlapping systems of phonological processing and working memory. Studies of focal brain lesions have partially elucidated the brain regions essential for these tasks; however relatively little information exists on the underlying functional neuroanatomy in the intact brain. We therefore examined the shared and separate neural systems of these tasks in two positron emission tomography (PET) experiments. In Experiment 1, eight healthy participants performed verbal DF, DB, and a sensorimotor control task during measurement of regional cerebral blood flow (rCBF). DF and DB each activated frontal, parietal, and cerebellar regions as well as prominently activating medial occipital cortex. To eliminate possible visuospatial confounds, Experiment 2 replicated the first experiment in six additional healthy participants who were blindfolded during the study. No differences in activation were found between the two experimental groups. Combined data from both experiments demonstrate that DF and DB rely upon a largely overlapping functional neural system associated with working memory, most notably right dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal lobule (IPL) as well as the anterior cingulate, a region associated with attentional effort. The degree of activation increased linearly with increasing task difficulty in DF. DB additionally recruited bilateral DLPFC, left IPL, and Broca's area. Medial occipital cortex (including higher and lower visual processing areas) was robustly activated in both DF and DB and could not be attributed to visual processing per se, suggesting a possible visual imagery strategy for these aural-verbal tasks.     

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.     

Inefficient neural activity in patients with schizophrenia and nonpsychotic relatives of schizophrenic patients: Evidence from a working memory task

Studies of schizophrenia with functional MRI have shown hyper- and hypoactivations in various brain regions including the prefrontal cortex. Functional anomalies have also been reported in first-degree relatives of schizophrenic patients. The aim of this study was to examine working memory related brain functions in healthy subjects, schizophrenic patients and unaffected relatives and to determine the influence of psychopathology on these processes. A parametric n-back working memory task and functional MRI were used to examine 61 patients with schizophrenia, 11 nonpsychotic relatives of schizophrenic patients and a comparison group of 61 healthy subjects. The results indicated increased as well as decreased brain functions in schizophrenic patients compared to the control group depending on the task difficulty and the performance: during the attention task (0-back), which served as control condition, behavioral responses of patients and healthy subjects hardly differed but BOLD responses were considerably enhanced in schizophrenic patients. With increasing task difficulty differences between groups in BOLD responses diminished whereas behavioral deficits of patients increased. The examination of attention-independent working memory-functions (2- vs. 0-back) produced hypoactivations in patients, especially in frontal, temporal and subcortical brain regions. Furthermore, positive symptoms were associated with parietal dysfunctions. Behavioral performance and neural responses of unaffected relatives of schizophrenic patients were intermediate between schizophrenic patients and controls indicating slight brain dysfunctions. In addition, compensatory strategies were demonstrated. These findings suggest that the genetic risk for schizophrenia is accompanied by neural inefficiency which is associated with cognitive deficits, especially in difficult tasks.     

Functional architecture of verbal and tonal working memory: an FMRI study

This study investigates the functional architecture of working memory (WM) for verbal and tonal information during rehearsal and articulatory suppression. Participants were presented with strings of four sung syllables with the task to remember either the pitches (tonal information) or the syllables (verbal information). Rehearsal of verbal, as well as of tonal information activated a network comprising ventrolateral premotor cortex (encroaching Broca's area), dorsal premotor cortex, the planum temporale, inferior parietal lobe, the anterior insula, subcortical structures (basal ganglia and thalamus), as well as the cerebellum. The topography of activations was virtually identical for the rehearsal of syllables and pitches, showing a remarkable overlap of the WM components for the rehearsal of verbal and tonal information. When the WM task was performed under articulatory suppression, activations in those areas decreased, while additional activations arose in anterior prefrontal areas. These prefrontal areas might contain additional storage components of verbal and tonal WM that are activated when auditory information cannot be rehearsed. As in the rehearsal conditions, the topography of activations under articulatory suppression was nearly identical for the verbal as compared to the tonal task. Results indicate that both the rehearsal of verbal and tonal information, as well as storage of verbal and tonal information relies on strongly overlapping neuronal networks. These networks appear to partly consist of sensorimotor-related circuits which provide resources for the representation and maintenance of information, and which are remarkably similar for the production of speech and song.     

Changes in neuronal activation in patients with bipolar disorder during performance of a working memory task

OBJECTIVES: Several lines of evidence suggest that deficits in cognition persist in bipolar patients during periods of euthymia. Working memory impairment has been observed in euthymic bipolar patients and noted to be a significant source of functional deficits in psychiatric disorders. Functional changes associated with these cognitive deficits however, remain poorly understood. We hypothesized that patients with bipolar disorder would demonstrate changes in neuronal activation in specific regions forming part of the working memory network. METHODS: Fifteen euthymic bipolar patients and fifteen age- and gender-matched healthy controls were recruited. Subjects participated in fMRI scans during which a two-back working memory task alternated with a zero-back control/attention task using a block-design paradigm. Groups were analyzed separately, and intergroup comparisons were made using an exploratory, voxel-by-voxel analysis. RESULTS: Bipolar patients performed more poorly on the cognitive tasks than did healthy controls (F = 3.77, p = 0.04). After covarying for task performance and reaction time, bipolar patients demonstrated significantly greater activation than healthy subjects in several regions including the fronto-polar prefrontal cortex, temporal cortex, basal ganglia, thalamus, and posterior parietal cortex. No areas showed a significant decrease in activation, compared with healthy controls. CONCLUSIONS: Our findings suggest that decreased working memory performance in bipolar patients reflects specific neurofunctional deficits. These deficits may represent primary areas of neuropathology or be secondary to neuropathology elsewhere in the working memory network. Continued research utilizing other imaging modalities may further clarify the underlying neuropathology involved in these cognitive deficits.     

Hippocampal underactivation in an fMRI study of word and face memory recognition in schizophrenia

Schizophrenia is a major mental disorder which is characterized by several cognitive deficits. Investigations of the neural basis of memory dysfunctions using neuroimaging techniques suggest that the hippocampus plays an important role in declarative memory impairment. The goal of this study was to investigate possible dysfunctions in cerebral activation in schizophrenic patients during both word and face recognition memory tasks. We tested 22 schizophrenics and 24 controls matched by gender, age, handedness and parental socioeconomic status. Compared to healthy volunteers, patients with schizophrenia showed decreased bilateral hippocampal activation during word and face recognition tasks. The whole brain analysis also showed a pattern of cortical and subcortical hypoactivation for both verbal and non-verbal recognition. This study provides further evidence of hippocampal involvement in declarative memory impairments of schizophrenia.     

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.     

Differential activation on fMRI of monozygotic twins discordant for AD

This is the first report of fMRI in monozygotic twins discordant for AD. FMRI brain activation patterns were examined during visuospatial and verbal working memory tasks. The affected twin had greater parietal involvement bilaterally during both working memory tasks and reduced left dorsolateral prefrontal cortex activity on the visuospatial memory task. Thus, fMRI may identify additional brain regions recruited in patients with AD to perform a given cognitive task.