Working memory in schizophrenia: dynamic visuo-spatial information processing

Working memory, commonly defined as the ability to hold mental representations on line transiently and to manipulate these representations, is known to be a core deficit in schizophrenia. The aim of the present study was to investigate the visuo-spatial component of the working memory in schizophrenia, and more precisely to what extent the dynamic visuo-spatial information processing is impaired in schizophrenia patients. For this purpose we used a computerized paradigm in which 29 patients with schizophrenia (DSMIV, Diagnostic Interview for Genetic Studies) and 29 age and sex matched control subjects (DIGS) had to memorize a plane moving across the computer screen and to identify the observed trajectory among 9 plots proposed together. Each trajectory could be seen max. 3 times if needed. The results showed no difference between schizophrenia patients and controls regarding the number of correct trajectory identified after the first presentation. However, when we determine the mean number of correct trajectories on the basis of 3 trials, we observed that schizophrenia patients are significantly less performant than controls (Mann-Whitney, p _ 0.002). These findings suggest that, although schizophrenia patients are able to memorize some dynamic trajectories as well as controls, they do not profit from the repetition of the trajectory presentation. These findings are congruent with the hypothesis that schizophrenia could induce an unbalance between local and global information processing: the patients may be able to focus on details of the trajectory which could allow them to find the right target (bottom-up processes), but may show difficulty to refer to previous experience in order to filter incoming information (top-down processes) and enhance their visuo-spatial working memory abilities.

Cerebellar lesions: is there a lateralisation effect on memory deficits?

BACKGROUND: Until recently, neurosurgeons eagerly removed cerebellar lesions without consideration of future cognitive impairment that might be caused by the resection. In children, transient cerebellar mutism after resection has lead to a diminished use of midline approaches and vermis transection, as well as reduced retraction of the cerebellar hemispheres. The role of the cerebellum in higher cognitive functions beyond coordination and motor control has recently attracted significant interest in the scientific community, and might change the neurosurgical approach to these lesions. The aim of this study was to investigate the specific effects of cerebellar lesions on memory, and to assess a possible lateralisation effect. METHODS: We studied 16 patients diagnosed with a cerebellar lesion, from January 1997 to April 2005, in the "Centre Hospitalier Universitaire Vaudois (CHUV)", Lausanne, Switzerland. Different neuropsychological tests assessing short term and anterograde memory, verbal and visuo-spatial modalities were performed pre-operatively. RESULTS: Severe memory deficits in at least one modality were identified in a majority (81%) of patients with cerebellar lesions. Only 1 patient (6%) had no memory deficit. In our series lateralisation of the lesion did not lead to a significant difference in verbal or visuo-spatial memory deficits. FINDINGS: These findings are consistent with findings in the literature concerning memory deficits in isolated cerebellar lesions. These can be explained by anatomical pathways. However, the cross-lateralisation theory cannot be demonstrated in our series. The high percentage of patients with a cerebellar lesion who demonstrate memory deficits should lead us to assess memory in all patients with cerebellar lesions.

Working memory load improves early stages of independent visual processing.

Increasing evidence suggests that working memory and perceptual processes are dynamically interrelated due to modulating activity in overlapping brain networks. However, the direct influence of working memory on the spatio-temporal brain dynamics of behaviorally relevant intervening information remains unclear. To investigate this issue, subjects performed a visual proximity grid perception task under three different visual-spatial working memory (VSWM) load conditions. VSWM load was manipulated by asking subjects to memorize the spatial locations of 6 or 3 disks. The grid was always presented between the encoding and recognition of the disk pattern. As a baseline condition, grid stimuli were presented without a VSWM context. VSWM load altered both perceptual performance and neural networks active during intervening grid encoding. Participants performed faster and more accurately on a challenging perceptual task under high VSWM load as compared to the low load and the baseline condition. Visual evoked potential (VEP) analyses identified changes in the configuration of the underlying sources in one particular period occurring 160-190 ms post-stimulus onset. Source analyses further showed an occipito-parietal down-regulation concurrent to the increased involvement of temporal and frontal resources in the high VSWM context. Together, these data suggest that cognitive control mechanisms supporting working memory may selectively enhance concurrent visual processing related to an independent goal. More broadly, our findings are in line with theoretical models implicating the engagement of frontal regions in synchronizing and optimizing mnemonic and perceptual resources towards multiple goals.

Metabolic connectivity as index of verbal working memory.

Positron emission tomography (PET) data are commonly analyzed in terms of regional intensity, while covariant information is not taken into account. Here, we searched for network correlates of healthy cognitive function in resting state PET data. PET with [(18)F]-fluorodeoxyglucose and a test of verbal working memory (WM) were administered to 35 young healthy adults. Metabolic connectivity was modeled at a group level using sparse inverse covariance estimation. Among 13 WM-relevant Brodmann areas (BAs), 6 appeared to be robustly connected. Connectivity within this network was significantly stronger in subjects with above-median WM performance. In respect to regional intensity, i.e., metabolism, no difference between groups was found. The results encourage examination of covariant patterns in FDG-PET data from non-neurodegenerative populations.

Development of the ability to inhibit a prepotent response: influence of working memory and processing speed.

This study aimed to examine developmental trends in response inhibition during childhood and to control for possible developmental influence of other basic cognitive processes (such as working memory and processing speed). In addition, we explored the relationships between response inhibition, working memory, and processing speed, as they are thought to be integral to cognitive control. Therefore, we assessed these three cognitive abilities in 159 children aged from 5 to 12. Results showed an improvement in response inhibition ability from 5 to 10 years of age. This improvement remained significant after controlling for the influence of working memory and processing speed. Furthermore, the developmental relationships showed an early differentiation between response inhibition, working memory, and processing speed. Thus, these processes were independent and need to be treated as such in further studies.

Does working memory training affect decision making ? : a neuroeconomic study

We all make decisions of varying levels of importance every day. Because making a decision implies that there are alternative choices to be considered, almost all decision involves some conflicts or dissatisfaction. Traditional economic models esteem that a person must weight the positive and negative outcomes of each option, and based on all these inferences, determines which option is the best for that particular situation. However, individuals rather act as irrational agents and tend to deviate from these rational choices. They somewhat evaluate the outcomes' subjective value, namely, when they face a risky choice leading to losses, people are inclined to have some preference for risk over certainty, while when facing a risky choice leading to gains, people often avoid to take risks and choose the most certain option. Yet, it is assumed that decision making is balanced between deliberative and emotional components. Distinct neural regions underpin these factors: the deliberative pathway that corresponds to executive functions, implies the activation of the prefrontal cortex, while the emotional pathway tends to activate the limbic system. These circuits appear to be altered in individuals with ADHD, and result, amongst others, in impaired decision making capacities. Their impulsive and inattentive behaviors are likely to be the cause of their irrational attitude towards risk taking. Still, a possible solution is to administrate these individuals a drug treatment, with the knowledge that it might have several side effects. However, an alternative treatment that relies on cognitive rehabilitation might be appropriate. This project was therefore aimed at investigate whether an intensive working memory training could have a spillover effect on decision making in adults with ADHD and in age-matched healthy controls. We designed a decision making task where the participants had to select an amount to gamble with the chance of 1/3 to win four times the chosen amount, while in the other cases they could loose their investment. Their performances were recorded using electroencephalography prior and after a one-month Dual N-Back training and the possible near and far transfer effects were investigated. Overall, we found that the performance during the gambling task was modulated by personality factors and by the importance of the symptoms at the pretest session. At posttest, we found that all individuals demonstrated an improvement on the Dual N-Back and on similar untrained dimensions. In addition, we discovered that not only the adults with ADHD showed a stable decrease of the symptomatology, as evaluated by the CAARS inventory, but this reduction was also detected in the control samples. In addition, Event-Related Potential (ERP) data are in favor of an change within prefrontal and parietal cortices. These results suggest that cognitive remediation can be effective in adults with ADHD, and in healthy controls. An important complement of this work would be the examination of the data in regard to the attentional networks, which could empower the fact that complex programs covering the remediation of several executive functions' dimensions is not required, a unique working memory training can be sufficient. -- Nous prenons tous chaque jour des décisions ayant des niveaux d'importance variables. Toutes les décisions ont une composante conflictuelle et d'insatisfaction, car prendre une décision implique qu'il y ait des choix alternatifs à considérer. Les modèles économiques traditionnels estiment qu'une personne doit peser les conséquences positives et négatives de chaque option et en se basant sur ces inférences, détermine quelle option est la meilleure dans une situation particulière. Cependant, les individus peuvent dévier de ces choix rationnels. Ils évaluent plutôt les valeur subjective des résultats, c'est-à-dire que lorsqu'ils sont face à un choix risqué pouvant les mener à des pertes, les gens ont tendance à avoir des préférences pour le risque à la place de la certitude, tandis que lorsqu'ils sont face à un choix risqué pouvant les conduire à un gain, ils évitent de prendre des risques et choisissent l'option la plus su^re. De nos jours, il est considéré que la prise de décision est balancée entre des composantes délibératives et émotionnelles. Ces facteurs sont sous-tendus par des régions neurales distinctes: le chemin délibératif, correspondant aux fonctions exécutives, implique l'activation du cortex préfrontal, tandis que le chemin émotionnel active le système limbique. Ces circuits semblent être dysfonctionnels chez les individus ayant un TDAH, et résulte, entre autres, en des capacités de prise de décision altérées. Leurs comportements impulsifs et inattentifs sont probablement la cause de ces attitudes irrationnelles face au risque. Cependant, une solution possible est de leur administrer un traitement médicamenteux, en prenant en compte les potentiels effets secondaires. Un traitement alternatif se reposant sur une réhabilitation cognitive pourrait être appropriée. Le but de ce projet est donc de déterminer si un entrainement intensif de la mémoire de travail peut avoir un effet sur la prise de décision chez des adultes ayant un TDAH et chez des contrôles sains du même âge. Nous avons conçu une tâche de prise de décision dans laquelle les participants devaient sélectionner un montant à jouer en ayant une chance sur trois de gagner quatre fois le montant choisi, alors que dans l'autre cas, ils pouvaient perdre leur investissement. Leurs performances ont été enregistrées en utilisant l'électroencéphalographie avant et après un entrainement d'un mois au Dual N-Back, et nous avons étudié les possibles effets de transfert. Dans l'ensemble, nous avons trouvé au pré-test que les performances au cours du jeu d'argent étaient modulées par les facteurs de personnalité, et par le degré des sympt^omes. Au post-test, nous avons non seulement trouvé que les adultes ayant un TDAH montraient une diminutions stable des symptômes, qui étaient évalués par le questionnaire du CAARS, mais que cette réduction était également perçue dans l'échantillon des contrôles. Les rsultats expérimentaux mesurés à l'aide de l'éléctroencéphalographie suggèrent un changement dans les cortex préfrontaux et pariétaux. Ces résultats suggèrent que la remédiation cognitive est efficace chez les adultes ayant un TDAH, mais produit aussi un effet chez les contrôles sains. Un complément important de ce travail pourrait examiner les données sur l'attention, qui pourraient renforcer l'idée qu'il n'est pas nécessaire d'utiliser des programmes complexes englobant la remédiation de plusieurs dimensions des fonctions exécutives, un simple entraiment de la mémoire de travail devrait suffire.

Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons.

Well-balanced mitochondrial fission and fusion processes are essential for nervous system development. Loss of function of the main mitochondrial fission mediator, dynamin-related protein 1 (Drp1), is lethal early during embryonic development or around birth, but the role of mitochondrial fission in adult neurons remains unclear. Here we show that inducible Drp1 ablation in neurons of the adult mouse forebrain results in progressive, neuronal subtype-specific alterations of mitochondrial morphology in the hippocampus that are marginally responsive to antioxidant treatment. Furthermore, DRP1 loss affects synaptic transmission and memory function. Although these changes culminate in hippocampal atrophy, they are not sufficient to cause neuronal cell death within 10 weeks of genetic Drp1 ablation. Collectively, our in vivo observations clarify the role of mitochondrial fission in neurons, demonstrating that Drp1 ablation in adult forebrain neurons compromises critical neuronal functions without causing overt neurodegeneration.

A la recherche de symptômes de désorientation dépendant d'un déficit d'intégration multisensorielle chez l'animal : un éclairage sur les mécanismes fondamentaux de la schizophrénie

Abstract Fundamental research in psychiatric neurosciences assumes that psychiatric disorders are associated with neurobiological factors. Identification of these factors would provide therapeutic targets as well as a better understanding of the relationship between- brain and behaviour in pathological processes. We conducted experiments in an animal model of schizophrenia. Several behavioural tasks were used to evaluate spatial and working memory in these animals. The model is based on glutathione deficit during cerebral development. Indeed, a 50% decrease of glutathione has been reported in prefrontal cortex of patients with schizophrenia. Glutathione is a major antioxidant in the brain and its deficit could lead to abnormal brain connectivity. The glutathione deficit was induced in rats by perinatal (PS-P16) subcutaneous injections with Lbuthionine-(S,R)-sullfoximine (BSO), an inhibitor of glutathione synthesis. This treatment leads to a transitory 50% glutathione levels during brain development. In parallel, we conducted behavioural testing in rats with a medial prefrontal cortex lesion. This allowed us to compare early damage induced by BSO treatment with a focal lesion in adults of a brain area known to present anomalies in schizophrenia. Finally, we conducted a series of experiments in senescent rats to evaluate if cognitive deficits could be related to neurobiological changes. Our results show that an early glutathione deficit provokes cognitive deficits in adulthood. These spatial and working memory deficits resemble the cognitive deficits observed in schizophrenia. The comparison with prefrontal rats revealed that the early brain glutathione deficit provoked more severe cognitive deficits than the prefrontal lesion in adult rats. Moreover, in both cases, we observed a dissociation in memory deficits depending on the type of locomotion that was used in behavioural experiments. Indeed, BSO treated rats as well as prefrontal rats showed place learning or working memory deficits in tasks conducted on dry surfaces where they had to walk. In contrast, they showed no deficit when the same cognitive functions were tested in the water maze. This dissociation might be sustained by a difference in requirement of sensory integration between walking and swimming tasks. Résumé La recherche fondamentale en neurosciences psychiatriques repose sur le présupposé selon lequel les symptômes manifestés dans les troubles psychiatriques auraient des concomitants neurobiologiques. Ceux-ci, une fois identifiés, offriraient des cibles pour une démarche thérapeutique ainsi que des modèles permettant de mieux comprendre les soubassements biologiques du comportement et des activités mentales. Nos expériences s'articulent autour de la question de la modélisation de la schizophrénie chez l'animal. Nous avons recherché chez ces animaux des troubles cognitifs et sensoriels associés à la schizophrénie. En effet, chez l'homme comme chez l'animal, la mémoire spatiale et la mémoire de travail dépendent fortement de la capacité d'intégration et d'organisation des informations sensorielles. Les premières expériences ont été menées suite à une perturbation périnatale du développement cérébral. Celle-ci visait à reproduire une diminution du taux de glutathion dans le cerveau, des recherches précédentes ayant observé une diminution de 50% du taux de glutathion dans le cortex préfrontal de patients schizophrènes. Le glutathion étant un antioxydant majeur dans le cerveau, son déficit pourrait conduire à des perturbations de la circuiterie cérébrale. Nous avons reproduit ce déficit chez le rat, par injection de Lbuthionine-(S,R)-sullfoximine (BSO), un inhibiteur de la synthèse du glutathion... Ce traitement a été administré pendant la période périnatale (du jour postnatal 5 au jour 16) provoquant une diminution de 50% du taux de glutathion. Nous avons ensuite évalué lës répercussions de cette atteinte précoce sur le comportement des rats à l'âge adulte. Ce modèle s'inscrit donc dans l'hypothèse neurodéveloppementale qui associe la schizophrénie à une atteinte du développement cérébral normal. Nous avons ensuite conduit des expériences similaires chez des rats ayant subi une lésion du cortex préfrontal pour comparer les répercussions du traitement périnatal avec une lésion, à l'âge adulte, d'une aire cérébrale connue pour présenter des anomalies chez les patients. Finalement, nous avons évalué si les processus sensoriels et cognitifs précédemment étudiés pouvaient également être affectés lors du vieillissement normal en recherchant des corrélats biologiques des déficits de mémoire liés à l'âge avancé. Nos résultats montrent que ce déficit précoce en glutathion peut avoir des répercussions surale comportement à l'âge adulte. On a relevé une similarité avec les déficits cognitifs associés.à la schizophrénie, incluant des déficits de mémoire de travail ainsi que des déficits de mémoire spatiale. Ces déficits étaient fortement liés au type de locomotion utilisée et n'ont été observés que dans les tâches où les animaux devaient rejoindre un but en marchant mais pas dans lés tests dans lesquels ils devaient localiser une cible en nageant. Les déficits induits par la lésion préfrontale chez l'adulte étaient beaucoup plus légers que ceux découlant de l'atteinte périnatale mais présentaient une dissociation analogue en fonction du type de locomotion. De plus, des tests similaires menés au cours du vieillissement confirment que la mémoire de travail peut être affectée sélectivement par le vieillissement dans une tâche où les animaux doivent marcher, tout en restant intacte dans le bassin de Morris. Les déficits cognitifs liés au vieillissement étaient significativement corrélés à des différences de niveaux des protéines post-synaptiques PSD95 (postsynaptic density 95). L'ensemble des résultats montre que les tests qui sont fréquemment utilisés pour évaluer la mémoire chez l'animal pourraient faire appel à des processus différents. Cette différence pourrait notamment tenir au niveau d'intégration sensorielle requis pour résoudre la tâche, qui est particulièrement sollicitée au cours d'une locomotion intermittente.

Schizophrenia connectivity: correlation between cognitive deficits and reduced thalamo-cortical fibers

Introduction: Schizophrenia is associated with multiple neuropsychological dysfunctions, such as disturbances of attention, memory, perceptual functioning, concept formation and executive processes. These cognitive functions are reported to depend on the integrity of the prefrontal and thalamo-prefrontal circuits. Multiple lines of evidence suggest that schizophrenia is related to abnormalities in neural circuitry and impaired structural connectivity. Here, we report a preliminary case-control study that showed a correlation between thalamo-frontal connections and several cognitive functions known to be impaired in schizophrenia. Materials and Methods: We investigated 9 schizophrenic patients (DSM IV criteria, Diagnostic Interview for Genetic Studies) and 9 age and sex matched control subjects. We obtained from each volunteer a DT-MRI dataset (3 T, _ _ 1,000 s/mm2), and a high resolution anatomic T1. The thalamo- frontal tracts are simulated with DTI tractography on these dataset, a method allowing inference of the main neural fiber tracks from Diffusion MRI data. In order to see an eventual correlation with the thalamo-frontal connections, every subject performs a battery of neuropsychological tests including computerized tests of attention (sustained attention, selective attention and reaction time), working memory tests (Plane test and the working memory sub-tests of the Wechsler Adult Intelligence Scale), a executive functioning task (Tower of Hanoï) and a test of visual binding abilities. Results: In a pilot case-control study (patients: n _ 9; controls: n _ 9), we showed that this methodology is appropriate and giving results in the excepted range. Considering the relation of the connectivity density and the neuropsychological data, a correlation between the number of thalamo- frontal fibers and the performance in the Tower of Hanoï was observed in the patients (Pearson correlation, r _ 0.76, p _ 0.05) but not in control subjects. In the most difficult item of the test, the least number of fibers corresponds to the worst performance of the test (fig. 2, number of supplementary movements of the elements necessary to realize the right configuration). It's interesting to note here that in an independent study, we showed that schizophrenia patients (n _ 32) perform in the most difficult item of the Tower of Hanoï (Mann-Whitney, p _ 0.005) significantly worse than control subjects (n _ 29). This has been observed in several others neuropsychological studies. Discussion: This pilot study of schizophrenia patients shows a correlation between the number of thalam-frontal fibers and the performance in the Tower of Hanoï, which is a planning and goal oriented actions task known to be associated with frontal dysfonction. This observation is consistent with the proposed impaired connectivity in schizophrenia. We aim to pursue the study with a larger sample in order to determine if other neuropsychological tests may be associated with the connectivity density.

Face Short-Term Memory-Related Electroencephalographic Patterns can Differentiate Multi- versus Single-Domain Amnestic Mild Cognitive Impairment.

Amnestic mild cognitive impairment (aMCI) is characterized by memory deficits alone (single-domain, sd-aMCI) or associated with other cognitive disabilities (multi-domain, md-aMCI). The present study assessed the patterns of electroencephalographic (EEG) activity during the encoding and retrieval phases of short-term memory in these two aMCI subtypes, to identify potential functional differences according to the neuropsychological profile. Continuous EEG was recorded in 43 aMCI patients, whose 16 sd-aMCI and 27 md-aMCI, and 36 age-matched controls (EC) during delayed match-to-sample tasks for face and letter stimuli. At encoding, attended stimuli elicited parietal alpha (8-12 Hz) power decrease (desynchronization), whereas distracting stimuli were associated with alpha power increase (synchronization) over right central sites. No difference was observed in parietal alpha desynchronization among the three groups. For attended faces, the alpha synchronization underlying suppression of distracting letters was reduced in both aMCI subgroups, but more severely in md-aMCI cases that differed significantly from EC. At retrieval, the early N250r recognition effect was significantly reduced for faces in md-aMCI as compared to both sd-aMCI and EC. The results suggest a differential alteration of working memory cerebral processes for faces in the two aMCI subtypes, face covert recognition processes being specifically altered in md-aMCI.

Representation of motor habit in a sequence of repetitive reach and grasp movements performed by macaque monkeys: evidence for a contribution of the dorsolateral prefrontal cortex.

In the context of an autologous cell transplantation study, a unilateral biopsy of cortical tissue was surgically performed from the right dorsolateral prefrontal cortex (dlPFC) in two intact adult macaque monkeys (dlPFC lesioned group), together with the implantation of a chronic chamber providing access to the left motor cortex. Three other monkeys were subjected to the same chronic chamber implantation, but without dlPFC biopsy (control group). All monkeys were initially trained to perform sequential manual dexterity tasks, requiring precision grip. The motor performance and the prehension's sequence (temporal order to grasp pellets from different spatial locations) were analysed for each hand. Following the surgery, transient and moderate deficits of manual dexterity per se occurred in both groups, indicating that they were not due to the dlPFC lesion (most likely related to the recording chamber implantation and/or general anaesthesia/medication). In contrast, changes of motor habit were observed for the sequential order of grasping in the two monkeys with dlPFC lesion only. The changes were more prominent in the monkey subjected to the largest lesion, supporting the notion of a specific effect of the dlPFC lesion on the motor habit of the monkeys. These observations are reminiscent of previous studies using conditional tasks with delay that have proposed a specialization of the dlPFC for visuo-spatial working memory, except that this is in a different context of "free-will", non-conditional manual dexterity task, without a component of working memory.

Programme de remédiation cognitive pour patients présentant une schizophrénie ou un trouble associé (Recos) : résultats préliminaires [Cognitive remediation program for individuals living with schizophrenia (Recos): preliminary results].

BACKGROUND: Nowadays, cognitive remediation is widely accepted as an effective treatment for patients with schizophrenia. In French-speaking countries, techniques used in cognitive remediation for patients with schizophrenia have been applied from those used for patients with cerebral injury. As cognitive impairment is a core feature of schizophrenia, the Département de psychiatrie du CHUV in Lausanne (DP-CHUV) intended to develop a cognitive remediation program for patients with a schizophrenia spectrum disease (Recos-Vianin, 2007). Numerous studies show that the specific cognitive deficits greatly differ from one patient to another. Consequently, Recos aims at providing individualized cognitive remediation therapy. In this feasibility trial, we measured the benefits of this individualized therapy for patients with schizophrenia. Before treatment, the patients were evaluated with a large battery of cognitive tests in order to determine which of the five specific training modules - Verbal memory, visuospatial memory and attention, working memory, selective attention, reasoning - could provide the best benefit depending on their deficit. OBJECTIVES: The study was designed to evaluate the benefits of the Recos program by comparing cognitive functioning before and after treatment. METHOD: Twenty-eight patients with schizophrenia spectrum disorders (schizophrenia [n=18], schizoaffective disorder [n=5], schizotypal disorder [n=4], schizophreniform disorder [n=1], DSM-IV-TR) participated in between one and three of the cognitive modules. The choice of the training module was based on the results of the cognitive tests obtained during the first evaluation. The patients participated in 20 training sessions per module (one session per week). At the end of the training period, the cognitive functioning of each patient was reevaluated by using the same neuropsychological battery. RESULTS: The results showed a greater improvement in the cognitive functions, which were specifically trained, compared to the cognitive functions, which were not trained. However, an improvement was also observed in both types of cognitive functions, suggesting an indirect cognitive gain. CONCLUSION: In our view, the great heterogeneity of the observed cognitive deficits in schizophrenia necessitates a detailed neuropsychological investigation as well as an individualized cognitive remediation therapy. These preliminary results need to be confirmed with a more extended sample of patients.

Visual binding abilities in the initial and advanced stages of schizophrenia

OBJECTIVE: The study tests the hypothesis that intramodal visual binding is disturbed in schizophrenia and should be detectable in all illness stages as a stable trait marker. METHOD: Three groups of patients (rehospitalized chronic schizophrenic, first admitted schizophrenic and schizotypal patients believed to be suffering from a pre-schizophrenic prodrome) and a group of normal control subjects were tested on three tasks targeting visual 'binding' abilities (Muller-Lyer's illusion and two figure detection tasks) in addition to control parameters such as reaction time, visual selective attention, Raven's test and two conventional cortical tasks of spatial working memory (SWM) and a global local test. RESULTS: Chronic patients had a decreased performance on the binding tests. Unexpectedly, the prodromal group exhibited an enhanced Gestalt extraction on these tests compared both to schizophrenic patients and to healthy subjects. Furthermore, chronic schizophrenia was associated with a poor performance on cortical tests of SWM, global local and on Raven. This association appears to be mediated by or linked to the chronicity of the illness. CONCLUSION: The study confirms a variety of neurocognitive deficits in schizophrenia which, however, in this sample seem to be linked to chronicity of illness. However, certain aspects of visual processing concerned with Gestalt extraction deserve attention as potential vulnerability- or prodrome- indicators. The initial hypothesis of the study is rejected.