The Virtual Tray of Objects Task as a novel method to electrophysiologically measure visuo-spatial recognition memory.

We explored a novel method to electrophysiologically measure visuo-spatial recognition memory using a modified version of the Virtual Tray of Objects Task (VTOT). Event-related potentials (ERP) were recorded from 18 healthy volunteers during performance in the VTOT. Participants were required to detect random repetitions of three-dimensional visual stimuli (OLD) and to refrain from responding to non-repeated stimuli (NEW). Differences in ERP between the NEW and OLD conditions were tested for statistical significance using assumption-free non-parametric analyses. Further, a correlation between ERP and behavioral measures was sought. Significant OLD-NEW effects were found for four ERP components showing distinct spatio-temporal characteristics: a posterior positive component appearing at 100 ms (P100), a left-lateralized negative component peaking at ≈250 ms (N250), a frontal negative component at ≈300-450 ms (FN400), and a right late frontal negativity (rLFN) at ≈500-720 ms. Moreover, individual differences in the OLD-NEW effect computed for the rLFN positively correlated with repeated stimulus recognition efficiency. However, there were no late left parietal P600 old/new effects. These findings suggest that the P100 component might reflect early visual perception processes taking place during performance in the task, whereas the N250 and FN400 components could be linked to stimulus-dependent access to visual memory representations and familiarity-related processes, respectively. In contrast, we propose that the rLFN component could be associated with higher-level cognitive functions, such as attention and monitoring processes. Altogether, our results suggest that the ERP version of the VTOT could play a role in the electrophysiological assessment of visuo-spatial memory and related sub-processes.

Mismatched expressions decrease face recognition and corresponding ERP old/new effects in schizophrenia.

OBJECTIVE: The objective was to investigate the electrophysiological (ERP) correlates of mismatched expression on face recognition in schizophrenia. METHOD: Expression-change effects and associated ERPs were explored in patients with schizophrenia (n = 20) and paired comparison participants (n = 20) on a long-term face-recognition task. RESULTS: A facial-expression change decreased discriminability for patients with schizophrenia than for healthy participants. The patients' recognition deficit was accompanied by the absence of the midfrontal FN400 and late parietal ERP old/new effects in the mismatched-expression condition. By contrast, preserved midfrontal FN400 and late parietal ERP old/new effects were found in both groups in the unchanged-expression condition. Thus, the preserved parietal old/new effect previously observed in schizophrenia was no longer found here in the situation in which expression changes took place between the study and recognition phases. CONCLUSIONS: These findings suggest that, when they are not supposed to take the change of expression into account, the recognition deficit observed here in patients with schizophrenia resulted from an impairment in the mechanisms underlying the emergence, assessment, or utilization of familiarity--as indexed by the ERP old/new effects. In these natural conditions, the impact of the expression change on the implementation of retrieval processes offers new insight into schizophrenia-linked deficits in face recognition, with substantial phenomenological differences with respect to the emergence of familiarity.

ERP investigation of study-test background mismatch during face recognition in schizophrenia.

Old/new effects on event-related potentials (ERP) were explored in 20 patients with schizophrenia and 20 paired comparison subjects during unfamiliar face recognition. Extrinsic perceptual changes - which influence the overall familiarity of an item while retaining face-intrinsic features for use in structural face encoding - were manipulated between the study phase and the test. The question raised here concerns whether these perceptual incongruities would have a different effect on the sense of familiarity and the corresponding behavioral and ERP measures in the two groups. The results showed that schizophrenia patients were more inclined to consider old faces shown against a new background as distractors. This drop in face familiarity was accompanied by the disappearance of ERP old/new effects in this condition, i.e., FN400 and parietal old/new effects. Indeed, while ERP old/new recognition effects were found in both groups when the picture of the face was physically identical to the one presented for study, the ERP correlates of recognition disappeared among patients when the background behind the face was different. This difficulty in disregarding a background change suggests that recognition among patients with schizophrenia is based on a global perceptual matching strategy rather than on the extraction of configural information from the face. The correlations observed between FN400 amplitude, the rejection of faces with a different background, and the reality-distortion scores support the idea that the recognition deficit found in schizophrenia results from early anomalies that are carried over onto the parietal ERP old/new effect. Face-extrinsic perceptual variations provide an opportune situation for gaining insight into the social difficulties that patients encounter throughout their lives.

Impairment not only in remembering but also in knowing previously seen faces and words in schizophrenia.

Patients with schizophrenia have pronounced deficits in face recognition memory that severely hamper their social skills. The functional mechanisms of these impairments remain unknown. According to the dual-process theory, recognition memory comprises two distinct components: recollection and familiarity. Studies using the Remember/Know procedure in patients with schizophrenia showed impairments in conscious recollection as measured by remember responses, but not in familiarity as measured by know responses. Unfortunately, none of these studies used face material. We investigated both recognition memory components using words and faces and the 'Remember/Know' procedure in 25 patients with schizophrenia and 24 control participants. In the same task, size congruency of stimuli was manipulated between the study and test phases to have a selective impact on know responses for faces. Patients reported fewer remember responses than controls. Size changes between the study and the test affected know responses in controls but not in patients. These results reveal that patients with schizophrenia are impaired in terms of their ability to recollect details about previously seen faces as they are for words.

Individual differences in face recognition memory: comparison among habitual short, average, and long sleepers.

Research indicates that habitual short sleepers show more rapid accumulation of slow-wave sleep at the beginning of the night. Enhancement in performance on declarative memory tasks has been associated with early NonREM sleep, consisting of the highest percentage of slow-wave sleep. Twenty-four subjects (eight short sleepers 7 but <9h, seven long >or=9h) were tested. Subjects were presented with unfamiliar face stimuli and asked to memorize them for a subsequent test. Following sleep, the subjects were presented with the 40 "old/studied" items intermixed with 40 new and asked to indicate the previously presented stimuli. Event-related potentials (ERPs) were analyzed to verify the existence of the "Old/New" effect, i.e. amplitude difference [in ERPs] between the old and new stimuli. ANOVA on the scores revealed a significant interaction between the stimuli and group. Post-hoc test on the studied items revealed more accurate responses in the short sleepers compared to the average and long sleepers. Strikingly, the long sleepers failed to show significant retention of the old/studied items, with their recognition of old faces not different from chance. Reaction time (RT) responses were faster for the old vs. the new items. Pearson correlation revealed a significant negative correlation between accuracy and sleep duration in the short sleepers. However, long and average sleepers showed a positive correlation between the two variables. ANOVA performed on the ERPs revealed main effects of stimuli and site, and no interactions involving the group factor. In conclusion, our data show that individual differences in recognition memory performance may be associated with differences in habitual sleep duration.

Relationship between psychotic and obsessive compulsive symptoms in schizophrenia.

The presence of obsessive compulsive symptoms (OCSs) in schizophrenia was recognized as early as the first descriptions of the illness. Studies investigating the association between OCSs and schizophrenia have defined their co-occurrence in terms of co-morbidity and compared schizophrenia patients separated into groups according to whether they presented OCSs or not. However, most of these studies did not take both the complexity of the schizophrenia phenomenology and that of OCSs into account. The present research investigates the relationship between schizophrenia symptoms and OCSs using a correlational approach with a dimensional perspective in order to determine how the OCSs contribute to symptom expression in schizophrenia. Fifty nine schizophrenia patients were rated for schizophrenia symptoms (SAPS-SANS) and OCSs (Y-BOCS). Schizophrenia symptoms scores were collapsed into four dimensional scores and OCSs into for other dimensional scores. The latter were entered as explanatory variables to determine their associations with schizophrenia dimension scores using series of stepwise regression models. The results showed a strong positive relationship between Delusions and Obsessions consistent with the view that they reflect manifestations of the similar mechanisms. Similar results indicate an association between Auditory hallucinations and Compulsions also suggesting that they share common mechanisms. On the other hand, there were inverse relationships between Somatic Obsessions and Disorganization and between Hoarding/Collecting Compulsions and Delusions or Auditory hallucinations. These results may reflect that these OCSs have a protective effect against disorganization and psychotic symptoms respectively.

Sex differences in memory processing in schizophrenia: an event-related potential (ERP) study.

Recently, research has begun to examine sex differences in cognitive functions in schizophrenia and whether such sex differences reflect normal, exaggerated, or reversed sexual dimorphism. This study examined this question by using event-related potentials (ERPs). ERPs were recorded in a recognition memory task in 18 patients and 18 matched control subjects. On an early frontal component, the results show an interaction between sex and pathological condition that results in an apparent reversed sexual dimorphism. On mid-latency components, patients show no sex difference on a frontal component, but a difference on the posterior component, whereas healthy subjects show a reverse pattern. Finally, late components show sex difference in the same direction as healthy subjects. These results indicate that the influence of sex on the cognitive impairment in schizophrenia is not homogenous across the information-processing cascade.

Temperament and executive dysfunctions in schizophrenia.

Recent studies suggest that both executive dysfunction and personality traits combine with symptoms to affect the social outcome of persons with schizophrenia. This study was designed to investigate how personality traits influence executive function in schizophrenia. Forty-four patients with schizophrenia and twenty-two healthy subjects were assessed for personality using the temperament and character inventory. Different aspects of executive function were assessed using the Auditory Digit Span (forward and backward) and the Wickens' test for proactive interference and release. The results showed that the influences of the various temperament dimensions on specific aspects of executive functions differ between patients and healthy subjects. On some dimensions, schizophrenia appears to reduce the cognitive differences related to temperament. On other dimensions, schizophrenia tends to reverse the cognitive differences related to temperament observed in healthy people. These results suggest that the temperamental profile of schizophrenia patients may well be of important prognostic value in the planning of cognitive enhancement therapy.

Event-related potentials differentiates the processes involved in the effects of sleep on recognition memory.

This study examined the role of sleep on event-related potential (ERP) indicators of memory following sleep and wake. We expected a larger ERP effect due to a facilitory effect of sleep on memory. During the study session, subjects memorized a series of stimuli (faces). At test, after a retention interval characterized by either sleep or by normal waking activities, subjects were asked to recognize old items intermixed with new. Results revealed differences in the old/new effect whereby the amplitude between old/new items was larger after sleep versus wake, suggesting a role of sleep in consolidation. Retention over sleep versus wake was associated with modified early and late frontal and posterior components possibly manifesting reduced interference inhibition, increased contextual processing, and facilitation of episodic memory. These findings suggest that ERP indices are differentially affected by sleep, reflecting differences in memory processing.

Intrusion errors in explicit memory: their differential relationship with clinical and social outcome in chronic schizophrenia.

INTRODUCTION: Memory deficits might account for clinical and adaptive differences between groups of patients with chronic schizophrenia. We investigated the qualitative factors of memory that influence clinical and social status. METHODS: Psychosocial functioning, clinical symptoms, and memory function were assessed in 99 patients at four time points over a 16-month period using recall scores for semantically related words, unrelated words, paired associated learning, and word span. An initial cluster analysis using symptom assessment data from all four time points divided the sample into three groups: patients with low symptoms ratings that remained stable throughout the study period (low symptom-stable group - LSSG; N=51); patients with initially high symptoms ratings that subsequently improved (high symptom-improved group - HSIG; N=32); and patients with initially high symptoms ratings that deteriorated during the follow-up (high symptom-deteriorated group - HSDG; N=16). RESULTS: Memory was better preserved in LSSG compared to HSIG and HSDG patients. Recall performance was generally better for semantically related words than for unrelated words but the difference between LSSG and the two other groups was more constant over time for semantically related words. Extra-list errors variable was positively correlated with three PANSS measures (r=.25-.47). Also, the extra-list errors scores were correlated with the Magical Ideation Scale (r=.34-.39). Memory scores (global explicit, unrelated, related) were significantly and positively correlated with independent living skills (r=.26-.55) and the extra-list errors were negatively correlated with both social support and independent living skills (r=-.29 and r=-.46, respectively). All groups showed a reduction in extraneous false recognition errors/intrusions (FRIs) over time with the HSIG showing the greater change. HSIG and HSDG patients committed slightly more FRIs in recall tasks (extraneous information) than LSSG patients. CONCLUSION: Memory performance is better in patients presenting with less severe symptomatology. The extent to which FRIs reduce over time in patients with schizophrenia is a novel finding.

Rivastigmine treatment as an add-on to antipsychotics in patients with schizophrenia and cognitive deficits.

OBJECTIVE: Although new atypical antipsychotic agents have been found to improve overall cognitive function in patients with schizophrenia (SZ), some aspects of memory, attention and executive functions still remain impaired. Acetylcholinesterase (AChE) inhibitors, such as rivastigmine, have been shown to improve cognition in other disorders, particularly Alzheimer's disease. Dysfunctions in cholinergic systems, especially in the prefrontal cortex, have been identified in SZ, suggesting that cholinesterase inhibitors may be effective in treating cognitive deficits in this disease. RESEARCH DESIGN AND METHODS: Using a randomized crossover design, we assessed SZ patients with stable symptoms and poor cognitive functioning. Fifty-eight patients with memory deficits, according to subjective complaints or based on clinicians' observations, were assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS). Only 24 of these subjects met the inclusion criteria. Twenty patients took part in the study (four dropped out). All subjects meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for SZ were maintained on their current antipsychotic medication (18 atypicals and two typicals) and were randomly assigned to treatment with rivastigmine. Dosage was a function of tolerability, beginning at 3 mg/day and progressively increasing to 9 mg/day. Subjects were given the Cambridge Neuropsychological Test Automated Battery (CANTAB) at baseline and 3 and 6 months. RESULTS: The results revealed no significant improvement in any of the cognitive variables investigated following rivastigmine treatment and symptom severity scores remained unchanged over all recorded time periods. CONCLUSION: Rivastigmine treatment did not appear to enhance cognition in SZ patients with important cognitive impairments. This finding needs to be interpreted with care and requires substantiation with larger sample size studies with patients treated with cognitive enhancer for longer periods.

Use of the process dissociation procedure to study the contextual effects on face recognition in schizophrenia: familiarity, associative recollection and discriminative recollection.

Contextual effects were explored in schizophrenia patients and paired comparison subjects during a long-term face recognition task. The objective was to investigate the contextual effects on face recognition by manipulating, in the same experiment, the perceptual context of the face (intrinsic vs. extrinsic) and the task context (inclusion vs. exclusion instructions). The situation was derived from the Jacoby's [Jacoby, L.L., 1991. A process dissociation framework: separating automatic from intentional uses of memory. Journal of Memory and Language 30, 513-541] process dissociation procedure. The results showed that schizophrenia patients (N=20) presented lower performances than healthy controls (N=20) in the inclusion but not in the exclusion task. This observation emphasizes the heterogeneity of recollection and suggests that the memory impairment in schizophrenia reflects an imbalance between two mechanisms. The first is a deficit in "associative recollection", i.e., the failure to use efficiently associative information. The other is an enhanced "discriminative recollection" that impedes their capacity to process information separately from its perceptual context. In addition, correlation with symptoms suggest that the former is expressed in the loosening of associations characteristic of disorganization symptoms, whereas the latter reflects the lack of flexibility or the contextualization bias related to psychotic symptoms, i.e., delusions and hallucinations.

Are cholinergic enhancers beneficial for memory in schizophrenia? An event-related potentials (ERPs) study of rivastigmine add-on therapy in a crossover trial.

Studies have reported beneficial effects of cholinergic enhancers, e.g., rivastigmine, on memory in schizophrenia but others have not. Possibly, these discrepancies are related to the lack of specificity of the tests used. This study investigated the effect of rivastigmine on memory in schizophrenia using event-related potentials (ERPs). Eighteen patients treated with atypical antipsychotic received rivastigmine adjuvant therapy in a randomized, crossover design. They were assessed at baseline (T1) and on two subsequent occasions (T2 and T3), where one half of the subjects were taken rivastigmine and the other half not. ERPs were recorded during a recognition memory task on each session. Behavioral and ERP data were analyzed using mixed ANOVA models first at T1 to detect potential group differences and for the trial (T1-T2) to determine the influence of rivastigmine, i.e., sessionxgroup interactions. The results showed no group difference at T1 except a trend for one group to be less efficient than the other on RT measures. When controlling for this difference the results on the trial data showed a trend for a benefit of rivastigmine on the RT memory effect. ERP analysis revealed that rivastigmine affects the amplitudes of two components elicited within 150-300 ms over posterior (reduced N2b) and frontal sites (enhanced P2a). It also enhances the magnitude of the memory (old/new) effect on two later components over posterior (N400) and frontal sites (F-N400). These results suggest that rivastigmine improves selective attention by enhancing interference inhibition processes (P2a) and lowering the reactivity to incoming stimulus (N2b). It also improves the integration of information with knowledge (N400) and with its context (F-N400). Generally, this study showed that the beneficial effect of rivastigmine on memory is not unitary but rather comes from its action at different time points within information processing cascade.

Are there common mechanisms in sensation seeking and reality distortion in schizophrenia? A study using memory event-related potentials.

A growing literature suggests that the characteristics of sensation seeking and reality distortion expressed in schizophrenia share several mechanisms. In a previous study, the comparison of patients with high vs. low reality distortion using event-related potentials (ERPs) recorded in a recognition memory task for unfamiliar faces identified neural and cognitive anomalies specifically related to the expression of these symptoms. As a follow-up, this study investigated the ERP correlates of sensation seeking in schizophrenia using the same recognition memory protocol. ERPs have been recorded in controls (N=21) and schizophrenia patients separated into high (HSS; N=13) and low (LSS; N=17) scorers according to Zuckerman's Sensation Seeking Scale. The results show a reduced P2a that was found unrelated to reality distortion in the previous study of reality distortion. It identifies interference inhibition impairment as being specifically related to sensation seeking. On the other hand, HSS scorers display enhanced fronto-central and normal P600 effects also found in high reality distortion patients. These results indicate inappropriate context processing and mnemonic binding common to sensation seeking and reality distortion. LSS scorers also display a reduced temporal N300 similar to that found in low reality distortion patients. This anomaly could reflect the lower reactivity to emotionally significant stimuli that underlies anhedonia symptoms. Finally, the N400 effect and a late frontal effect are found in both HSS and LSS. Since they were unrelated to reality distortion, these indices have been related to basic aspects of schizophrenia, e.g., deficient knowledge integration, or other mechanisms, e.g. anxiety or impulsivity. In summary, the present study examines the strategy of investigating variables, such as temperamental characteristics, in addition to symptoms, to show how discrete impairments may contribute to the expression of the illness.

The relationships between symptom dimensions and dysphoria in schizophrenia.

Previous studies have suggested that qualitatively distinct aspects of dysphoria (anxiety and depression) are related to specific dimension of schizophrenia symptomatology. Most of these studies used simple dimensions and dysphoria models, although finer distinctions could help defining specific relationships. This study examined the relationships of distinctive aspects of depression and anxiety (both state and trait) with symptom dimensions. Forty patients with a DSM-IV diagnosis of schizophrenia were assessed for symptoms (SAPS-SANS), trait and state anxiety (STAI) and depression (CDS). Symptoms ratings were summarized as dimensional scores according to a two-, three- or five-dimensional models proposed in the literature. The correlation analysis replicates previous observations that distinct aspects of dysphoria are associated with specific dimensions of schizophrenia, with the exception of disorganization. Moreover, controlling for intercorrelated variables revealed that schizophrenia and dysphoric symptoms might act in combination and/or through indirect links to contribute to illness expression. Our data further suggested that these associations may be best understood in terms of interactions between various processing biases alluded in the most recent cognitive accounts of schizophrenia symptoms.

Gender differences in memory processing: evidence from event-related potentials to faces.

This study investigated gender differences on memory processing using event-related potentials (ERPs). Behavioral data and ERPs were recorded in 16 males and 10 females during a recognition memory task for faces. The behavioral data results showed that females performed better than males. Gender differences on ERPs were evidenced over anterior locations and involve the modulation of two spatially and temporally distinct components. These results are in general accordance with the view that males and females differ in the cognitive strategies they use to process information. Specifically, they could differ in their abilities to maintain information over interference and in the processing of the intrinsic contextual attributes of items, respectively, associated with the modulation of two anterior components. These interpretations lend support to the view that processing in females entails more detailed elaboration of information content than in males. Processing in males is more likely driven by schemas or overall information theme.

Changes in the neuropsychological correlates of clinical dimensions between the acute and stable phase of schizophrenia.

This study was designed to investigate whether the neuropsychological correlates of the symptom dimensions of schizophrenia vary with the clinical state in patients followed from the acute to stable the phase of the illness. Fifteen patients were assessed for symptoms (SAPS-SANS) and undergone a complete neuropsychological assessment at two sessions. The first session (S1) was carried out within six days after admission, i.e., acute phase and the second (S2) at least two month after hospitalization, i.e., stable phase. The data were analyzed using stepwise regression models in which neuropsychological scores were in entered to predict each dimensional score. This analysis was applied on the S1 and S2 data as well as on the S2-S1 difference to assess the neuropsychological predictors of clinical changes. Generally, the results replicate the previous associations between neuropsychological and dimensional measures found in stable patients. In addition, this study shows if each dimension appears to rely on a key structure, symptom variations seems to involve changes in the spread of the dysfunction and/or changes in the connectivity between the key and other regions. The results also suggest that functional changes related to some symptoms dimensions occur to compensate for the dysfunction associated with other symptoms.

The cognitive and anatomo-functional basis of reality distortion in schizophrenia: a view from memory event-related potentials.

This study investigated the neural and cognitive correlates of reality distortion in schizophrenia by using event-related potentials (ERPs) recorded in a recognition memory task for face. This task has been chosen because previous studies have shown that it provides distinct indices related to specific cognitive processes and to the functioning of specific brain regions. ERPs have been recorded in controls and schizophrenia patients separated into high scorers (RD+) and low-scorers (RD-) according to their Reality Distortion score (hallucination and delusion SAPS subscales). The results indicate that RD+ presents abnormalities on various cognitive processes. First, RD+ are deficient at interference inhibition and knowledge integration (reduced P2a and N400 effect). The similar impairments found in RD- suggest that they represent basic traits of the illness. Second, RD+ showed inappropriate stimulus categorization and contextual integration (larger N300 and fronto-central effect). Third, RD+ showed a late index (P600 effect) not different from controls, but larger than in RD-. This result is consistent with a qualitative, rather than quantitative, impairment of mnemonic binding processes (inappropriate binding) in RD+. Since each of the ERP abnormalities observed represents associated with distinct brain dysfunction, the results are further discussed in regard of the respective contribution of the parietal, frontal and hippocampal structures to reality distortion symptoms.

The dimensional symptom structure of schizophrenia and its association with temperament and character.

Recent studies suggest that personality may influence symptom expression and social functioning in schizophrenia. This study investigated the relationships between personality and symptom dimensions in schizophrenia patients. Fifty-two schizophrenia patients and 25 five healthy subjects were assessed using the Temperament and Character Inventory (TCI). The patients were also assessed for positive and negative symptoms using SAPS and SANS and scored according to Andreasen's (1995: Andreasen, N.C., Arndt, S., Alliger, R., Miller, D., Flaum, M. 1995. Symptoms of schizophrenia. Methods, meanings, and mechanisms. Arch. Gen. Psychiatry, 52, 341-351) classical three dimensional model and by the five dimensional model of Toomey et al. (1997: Toomey, R., Kremen, W.S., Simpson J.C., Samson, J.A., Seidman, L.J., Lyons, M.J., Faraone, S.V., Tsuang, M.T. 1997. Revisiting the factor structure for positive and negative symptoms: evidence from a large heterogeneous group of psychiatric patients. Am. J. Psychiatry, 154, 371-377). Comparisons between patients and controls revealed significant differences on various TCI scores consistent with a global disorganization of personality in schizophrenia involving both basic neurophysiological and potentially genetically determined traits (i.e. temperament) and developmental aspects of personality (i.e. character). Correlation analysis showed distinct associations between symptoms and personality dimensions. The results suggest that the negative and disorganized dimensions of schizophrenia are related temperamental factors, whereas the psychotic symptoms are more related to characterological abnormalities. The observed patterns of associations also underline the heterogeneity of the classical negative and positive dimensions of schizophrenia.