Benzodiazepine long-term administration is associated with impaired attention/working memory in schizophrenia: results from the national multicentre FACE-SZ data set.

OBJECTIVE: The effect of benzodiazepine long-term administration (BLTA) in cognitive functioning of subjects with schizophrenia (SZ) has been partially explored to date. The objective was to assess BLTA-associated cognitive impairment with a comprehensive cognitive battery in a non-selected multicentric/national community-dwelling sample of stabilized SZ subjects. METHOD: 407 community-dwelling stabilized SZ subjects were consecutively included in the FondaMental Academic Centers of Expertise for Schizophrenia Cohort (FACE-SZ). Patients taking daily benzodiazepine were defined as BLTA+ as all patients examined by the Expert Center were clinically stabilized and under stable dose of treatment for at least 3 months. Each patient has been administered a 1-day long comprehensive cognitive battery (including The National Adult Reading Test, the Wechsler Adult Intelligence Scale, the Trail Making Test, the California Verbal Learning Test, the Doors test, and The Continuous Performance Test-Identical Pairs). RESULTS: In the multivariate analyses, results showed that BLTA was associated with impaired attention/working memory (OR 0.60, 95% confidence interval 0.42-0.86; p = 0.005) independently of socio-demographic variables and illness characteristics. Verbal and performance current IQ-[respectively, OR 0.98, 95% CI (0.96;0.99), p = 0.016 and 0.98, 95% CI(0.97;0.99), p = 0.034] but not premorbid IQ-(p > 0.05) have been associated with BLTA in a multivariate model including the same confounding variables. CONCLUSION: BLTA is associated with impaired attention/working memory in schizophrenia. The BLTA benefit/risk ratio should be regularly reevaluated. Alternative pharmacological and non-pharmacological strategies for comorbid anxiety disorders and sleep disorders should be preferred when possible. It seems reasonable to withdraw BLTA before the start of cognitive remediation therapy, as soon as possible, to improve the effectiveness of this therapy. Limits: the delay between the last benzodiazepine intake and testing, as well as the specific class of benzodiazepines (long half-life vs. short half-life), and the number of benzodiazepine daily intakes have not been recorded in the present study. The precise motive for BLTA prescription and sleep disturbances have not been reported, which is a limit for the interpretation of the present results.

[Autobiographical memory and self-disorders in schizophrenia]. / Les troubles de la mémoire autobiographique et du self dans la schizophrénie.

OBJECTIVES: Disorders of self in schizophrenia have been considered as the core feature of the illness since its early clinical description. However, until recently, the understanding of these disorders referred mostly to philosophical considerations. The aim of this work is to examine how the various aspects of autobiographical memory deficits may be considered as possible cognitive mechanisms accounting for self-disorders in patients. METHODS: We performed a theoretical review of the literature on autobiographical memory studies in schizophrenia. Our approach of cognitive psychopathology was grounded in the model of the Self-Memory System put forward by Conway (2005), which posits reciprocal relationships between autobiographical memory and the self. This model stresses the distinction between the working-self and the autobiographical memory knowledge base. The latter contains all autobiographical information stored in our life and is organized according to the specificity of this information. The role of the working-self is to maintain the coherence of the self and to control the access to autobiographical memories and corresponding memory details. The working-self supports an experiential or phenomenological dimension of the self, especially when a highly detailed autobiographical memory is retrieved, and a past event is re-experienced by the rememberer. The working-self also entails a conceptual part, the conceptual self, which contains self-knowledge and self-images. RESULTS: Our review showed that autobiographical memories of patients with schizophrenia are less specific and contain fewer phenomenological details than those of healthy participants. Patients also have difficulty assessing the subjective temporal distance of past events, and their ability to re-experience unique past personal events is affected as shown by a reduced conscious recollection and a smaller frequency of Field visual perspective during recall of autobiographical memories. This global alteration of all phenomenological characteristics of autobiographical memories strongly suggests an alteration of the phenomenological dimension of the self in schizophrenia. Since some of these alterations are also found in patients when they plan for future personal events, the ability to mentally travel in time is reduced in patients and reflects an impaired sense of self across time. The literature also shows that self-images are more passive, less coherent and less stable in time in patients compared to healthy participants. These results point to an alteration of the conceptual dimension of the self in schizophrenia. This may be partly explained by a weaker connection between the self and autobiographical memory and by other alterations of autobiographical memories closely linked to the self. In fact, the reminiscence bump is disorganized in patients and comprises poorly detailed memories. Memories grounding self-images are less organized and weakly connected to self-images. Finally, patients have an impaired ability to give a meaning to or to draw lessons from self-defining memories of their life. CONCLUSION: Based on these results, we discuss current and future therapeutic interventions including both cognitive remediation methods and cognitive psychotherapy applied to autobiographical memory. These methods appear relevant to help patients improve both the sense of self associatied with their autobiographical memory retrieval and the coherence and stability of the self.

Self-continuity across time in schizophrenia: An exploration of phenomenological and narrative continuity in the past and future.

BACKGROUND: Disorders of the self, such as a reduced sense of personal continuity in time, are a core symptom of schizophrenia, but one that is still poorly understood. In the present study, we investigated two complementary aspects of self-continuity, namely phenomenological and narrative continuity, in 27 patients with schizophrenia, and compared them with 27 control participants. METHODS: Participants were asked to identify important past events and to narrate a story from their life that included these events. They were also asked to imagine important events that might happen in their personal future and to build a narrative of their future life. The vividness of these important life events and the proportion of self-event connections in the narratives were used as a measure of phenomenological and narrative continuity, respectively. RESULTS: Our study showed patients with schizophrenia experienced less vivid representations of personally significant events (p = .02) for both temporal directions (past and future) (p < .001). In addition, their ability to make explicit connections between personal events and self-attributes in life narratives was also impaired (p = .03), but only in the case of past narratives (p < .001). CONCLUSIONS: These results shed new light on the cognitive mechanisms underlying self-disorders in schizophrenia. The clinical and therapeutic implications of these findings are discussed.

Grasping the mechanisms of narratives' incoherence in schizophrenia: an analysis of the temporal structure of patients' life story.

OBJECTIVE: Life narratives of patients with schizophrenia are characterized by impaired coherence so that the listener has often difficulties to grasp the life trajectory of the patients. In order to better understand what causes this reduced temporal coherence, we investigated the temporal structure of patients' life narratives through different temporal narrative elements (elaboration of beginnings and endings, local temporal indicators and temporal deviations from a linear order), across two complementary studies. METHODS: Life narratives were collected by means of two different methods; a free recall in study 1 and a more structured protocol, aiming at reducing the cognitive task demands in study 2. All narratives from the two studies were analyzed using the same validated method. RESULTS: Both studies showed that global temporal coherence is significantly reduced in patients with schizophrenia (ps.02). This is mainly due to their stronger tendency to temporally deviate from a linear temporal order without marking the deviation as such. We also observed significant correlations in the patient groups between global temporal coherence and executive dysfunction (p=.008) or their higher tendency to temporally deviate from a linear temporal order in their life narratives (p<.001). CONCLUSIONS: These results shed light on narrative correlates of temporal narrative incoherence in schizophrenia and highlight the central role of executive dysfunction in this incoherence.

[Theoretical reflection on the place of memory and temporal cognitive mechanisms in addictive disorders]. / Réflexion théorique sur la place des mécanismes cognitifs mnésiques et temporels dans l'addiction.

INTRODUCTION: Addictions can be regarded as cognitive disorders related to neurobiological impairments. On the one hand, some cognitive impairments occur as a result of substance intake and withdrawal upon stopping intake, while, on the other hand, cognitive mechanisms are responsible for initiating and maintaining addiction. In this review, we detail the memory and temporal mechanisms involved in this pathology. METHODOLOGY: We reviewed the literature dedicated to the mechanisms of conditioning association between a substance and a context, and the memory and temporal mechanisms involved in the maintenance of addiction. Cognitive impairments in this context are accompanied by both short-term and long-term neurobiological disorders. RESULTS: Drug-context conditioning is dependent on learning abilities in rats and humans, and it is the first step towards the development of an addiction. In fact, with the beginning of an addiction, it is the context associated with the substance intake, which determines the reinforcing factors (such as pleasure in the case of drug consumption) for the development of an addiction. Maintenance of addiction is related to the persistence of this association between context and substance. Furthermore, the impulsiveness of patients renders them unable to delay their gratification. Consequently, even if delayed gratifications are more valuable, patients prefer immediate gratification such as substance use. DISCUSSION: The memory and temporal mechanisms of addiction are central to the initiation and maintenance of drug addiction. They also affect patients' ability to develop projects for the future. The salience of the memory association between drug and context is accompanied by a decline in autobiographical memories, which become poor and lacking in detail. It is probably these impairments which are responsible for the difficulty that the patients have while investigating their story during psychotherapy. On the other hand, given that even though delayed gratification is greater patients prefer immediate gratification, they have difficulty making plans for the future and constructing their own personality. These cognitive impairments are sustained by neurobiological correlates such as dopamine dysregulation in the short-term and changes in neural plasticity in the cortico-meso-limbic system in the long term. CONCLUSION: We reviewed full arguments which highlight that addiction is mediated by cognitive mechanisms which are related on the one hand to clinical symptoms and, on the other hand, to neurobiological alterations. According to the literature, memory and time mechanisms seem to be central to the initiation and maintenance of addictive behaviours. More research is needed to improve our knowledge of the cognitive mechanisms of addiction and to develop new tools for treating patients.

[Functioning of memory in subjects with autism]. / Fonctionnement de la mémoire chez les sujets avec autisme.

INTRODUCTION: Autism is an early developmental disorder with cognitive impairments that leads to learning and social integration disabilities. The characterization of memory functions in individuals with autism has been the subject of numerous investigations, with widely varying conclusions. The notable differences between these studies can be attributed to variations in the age, intelligence and level of severity of the participants with autism. LITERATURE FINDINGS: The purpose of our review of the recent literature is to describe the memory function of individuals with autism. Some of the different memory subtypes are intact, others are impaired. Short-term memory (digit span) is not impaired while working memory is impaired in some of its components, but the findings are inconsistent. More recent studies demonstrate reduced spatial working memory abilities in autism and extend previous findings by demonstrating that these deficits are significant when tasks impose heavier demands on working memory. Episodic long-term memory, as measured by free recall, cued recall or recognition tasks, is intact, but participants with autism perform significantly less well than controls as the complexity of the verbal or visual material to be recalled increases. Source or contextual memory involves a variety of characteristics specifying the conditions under which specific items or facts are acquired: it has been investigated in individuals with autism with different methods. Deficits in source memory for temporal information have been found, but there were no reality monitoring deficits. Recent findings indicate that the nature of source memory confusion in autism does not appear to reflect a generalized deficit in attaching context to memories, but rather is dependant on the specific to-be-remembered information that involves social aspects of context. The self-reference effect is missing, with individuals with autism recalling events performed by themselves less well than the events performed by a peer, suggesting they have difficulties in relation to processes involving the self. Studies involving assessment of subjective states of awareness during recognition show less conscious recollection and more feelings of familiarity. Recent investigations are consistent in demonstrating memory impairments related to the failure of subjects with autism to use organizing strategies or meaning to support memory, an effect which grows with the increasing complexity of the material. Memory deficits in autism may be related more to retrieval and less to encoding, as deficit in source memory in participants with autism is largely eliminated when source was supported at test. DISCUSSION: The neuroanatomical basis of the specificities of memory impairment in autism is still uncertain, but it is suggested that autism involves an impairment in the conversion of limbic inputs into medial prefrontal outputs. Memory deficits found in individuals with autism may explain some of the clinical symptoms. Failure to encode all the information, especially its social aspects, may therefore contribute to dysfunction in the social, communication, and reasoning domains. Abnormal memory functioning in autism is also related to more general cognitive impairments, including executive function deficits and central coherence weakness. Evidence of the normality of certain memory capacities, at least in individuals with moderate autistic symptomatology, is encouraging for adaptive improvements in cognitive functioning.

Functional mechanisms underlying impaired recognition memory and conscious awareness in patients with schizophrenia.

BACKGROUND: Schizophrenia impairs episodic memory in its critical feature, autonoetic awareness, i.e., the type of awareness that is characterized by mentally reliving events from one's personal past. It spares noetic awareness, another form of awareness based on feelings of familiarity. We investigated the hypothesis that the impairment of autonoetic awareness is related to defective information that binds together separate aspects of events. METHODS: An experiential approach to recognition memory was used. Twenty-five patients with schizophrenia and 25 normal subjects performed or watched actions consisting of pairing objects. Then, they had to recognize pairs of objects and who paired them (source recognition). Subjects were also asked to provide a "remember" (autonoetic awareness) or a "know" (noetic awareness) response according to their subjective state at the time they recognized each pair of objects and each source. RESULTS: Patients exhibited an impaired recognition memory. When actions were observed, recognition of pairs of objects, but not of source, was no better than chance. There was a reduction in frequency of autonoetic awareness, its consistency throughout recognition of objects and source, and its relationship to source discrimination accuracy. Recognition was based largely on noetic awareness. CONCLUSIONS: Patients with schizophrenia are unable to link the separate aspects of events into a cohesive, memorable, and distinctive whole. The corollary of this defective relational binding is a quantitative and qualitative impairment of autonoetic awareness.

Explicit memory and repetition priming in depression. Preliminary findings.

Explicit memory and repetition priming, a form of implicit memory, were examined in depressed patients and controls. Explicit memory of depressed patients was severely impaired, whereas repetition priming was intact. These results are consistent with the hypothesis that the impairment of memory in depression is linked to a failure of effort-demanding cognitive processes. Repetition priming might be useful in differentiating between depression and dementia.

Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset.

The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio=2.04, p=.025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications.

Improvement of schizophrenic patients with primary negative symptoms treated with amisulpride. Amisulpride Study Group.

OBJECTIVE: The goal of this placebo-controlled study was to evaluate the efficacy and safety of low doses of amisulpride, an atypical antipsychotic of the benzamide class with high affinity for D2 and D3 dopamine receptors, in the treatment of schizophrenic patients with predominantly primary negative symptoms. METHOD: After completion of a 4-week washout period, schizophrenic patients with primary negative symptoms participated in a 12-week, multicenter double-blind trial of placebo (N = 83), amisulpride, 50 mg/day (N = 84), or amisulpride, 100 mg/day (N = 75). They were evaluated with the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Brief Psychiatric Rating Scale, and the Montgomery-Asberg Depression Rating Scale. RESULTS: Both amisulpride treatment groups showed significantly greater improvement in negative symptoms than the placebo group. Positive symptom scores were low at baseline and changed minimally during the study, suggesting that the improvement in negative symptoms was independent of improvement in positive symptoms. The safety of amisulpride was comparable to that of placebo, and extrapyramidal symptoms were infrequent. Comparable efficacy and safety results were observed with either dose of amisulpride. CONCLUSIONS: These findings confirm and extend those of earlier placebo-controlled studies of low-dose amisulpride in the treatment of patients with predominantly negative symptoms of schizophrenia.

Intact implicit learning in schizophrenia.

OBJECTIVE: Schizophrenia impairs performance on explicit, but not implicit, memory tasks, indicating that conscious awareness at retrieval is a critical determinant of impaired memory. The authors investigated implicit learning, i.e., knowledge acquisition in the absence of conscious awareness, in patients with schizophrenia. METHOD: An artificial grammar learning task was used to assess implicit learning in 48 patients with schizophrenia and 24 healthy comparison subjects. The subjects were first presented with letter strings that were generated according to the rules of a finite-state grammar paradigm. They were then required to indicate whether new letter strings were "grammatical," depending on whether or not the strings corresponded to the rules. IQ, working memory, explicit memory, verbal fluency, and speed of processing were also assessed. RESULTS: Patients performed significantly worse than the comparison subjects on cognitive tasks that assessed episodic memory, verbal fluency, working memory, and speed of processing. In contrast, patients classified as being correct more grammatical than nongrammatical letter strings, and the magnitude of the difference was similar to that observed in healthy comparison subjects. CONCLUSIONS: Implicit learning, as assessed with an artificial grammar learning task, is intact in patients with schizophrenia. Conscious awareness might be a critical determinant of memory impairment both at encoding and at retrieval.

Defective relationship between subjective experience and behavior in schizophrenia.

OBJECTIVE: The relationship between subjective experience and behavior abnormalities in schizophrenia was investigated. METHOD: Eighteen patients with schizophrenia and 18 normal comparison subjects completed a general knowledge task with two incentive conditions to measure monitoring effectiveness, control sensitivity, and response criterion setting. RESULTS: The patients' levels of monitoring effectiveness and control sensitivity were lower than those of the comparison subjects. The effect of incentives on response criterion values was similar in the two groups. CONCLUSIONS: Patients were impaired in subjectively assessing the correctness of their knowledge, and their behavior was less determined by subjective experience than that of normal subjects. The patients' intact sensitivity to incentives has implications for cognitive remediation.

Impairment of recognition memory with, but not without, conscious recollection in schizophrenia.

OBJECTIVE: To test the hypothesis that there is a link between the memory deficit associated with schizophrenia and an impairment of consciousness, an experiential approach was used to assess recognition memory and awareness in schizophrenic patients and normal subjects. METHOD: On a recognition memory task with low- and high-frequency words, the schizophrenic (N = 30) and normal (N = 30) subjects gave "remember" responses to recognized items that were accompanied by conscious recollection and "know" responses to items that were recognized on the basis of familiarity without any recollective experience. RESULTS: Schizophrenia selectively impaired recognition based on recollective experience, as measured by "remember" responses, but had no effects on "know" responses. In the comparison group, low-frequency words, relative to high-frequency words, enhanced conscious recollection but not familiarity. The schizophrenic patients did not display the same word-frequency effect. CONCLUSIONS: These results indicate that schizophrenia affects differentially two means of access to the personal past: it impairs recognition memory with, but not without, conscious recollection. They suggest that the impairment of conscious recollection observed in schizophrenic patients could be due to a failure of elaborative processing of information.

Working memory control in patients with schizophrenia: a PET study during a random number generation task.

OBJECTIVE: The authors' goal was to investigate brain regions involved in the deficiency of working memory control processes in patients with schizophrenia. METHOD: Regional cerebral blood flow was measured with positron emission tomography in eight men with stabilized schizophrenia and eight healthy men while they were performing a graded random number generation task. Twelve scans were made for each subject. Covariations between randomness of responses and regional activation were analyzed. RESULTS: The pattern of covariation between randomness of responses and activation in the anterior cingulate and superior parietal regions differed between patients and healthy subjects. CONCLUSIONS: These results suggest a cinguloparietal dysfunction underlying the impairment of working memory control processes during a random number generation task in patients with schizophrenia.

Lorazepam and diazepam impair true, but not false, recognition in healthy volunteers.

RATIONALE: The deleterious effects of benzodiazepine on memory are well documented. However, their effects on false memories are unknown. OBJECTIVE: The aim of this study was to investigate the effects of lorazepam and diazepam on false memories and related states of awareness in healthy volunteers. METHODS: The Deese/Roediger-McDermott procedure was used in 36 healthy volunteers randomly assigned to one of three parallel groups (placebo, diazepam 0.3 mg/kg, lorazepam 0.038 mg/kg). Subjects studied lists of words semantically related to a non-presented theme word (critical lure). On a recognition memory task with both previously presented words and non presented critical lures, they were asked to give Remember, Know or Guess responses to items that were recognized on the basis of conscious recollection, familiarity, or guessing, respectively. RESULTS: The proportions of studied words correctly recognized and the proportions of Remember responses associated with true recognition were lower in the benzodiazepine groups than in the placebo group. In contrast, benzodiazepines did not significantly influence the proportions of critical lures falsely recognized or the proportions of Remember responses associated with false recognition. CONCLUSION: These results indicate that diazepam and lorazepam impair conscious recollection associated with true, but not false, memories.

Effects of lorazepam on perceptual integration of visual forms in healthy volunteers.

We tested whether lorazepam (a benzodiazepine) affects perceptual processes involved in the computation of contour information. Subjects matched incomplete forms whose contour was composed of line segments varying in their spacing and in their alignment. An initial centrally displayed object (a reference) was followed by two laterally displayed pictures, a target and a distractor. The distractor was the mirror-reversed version of the target. In one condition, the reference was always an outline drawing of an object. In another condition, the reference was either an outline drawing or an incomplete form. All subjects were run in both conditions. Lorazepam 0.038 mg/kg induced a larger increase in RTs than the placebo and lorazepam 0.026 mg/kg when the spacing between local contour elements was larger than 10.8' arc and when the line segments were not aligned. Performance was improved in the 0.038 mg/kg lorazepam group when subjects started with the condition in which the reference was always an outline drawing. Performance was not correlated with sedation. These results show that lorazepam impairs visual perception. They are interpreted in terms of impaired binding processes, which can be compensated for by the use of stored object representations. This effect is consistent with electrophysiological studies showing that the neuromediator GABA is involved in perceptual processes.

Effect of a subanesthetic dose of ketamine on memory and conscious awareness in healthy volunteers.

RATIONALE: Ketamine is an NMDA receptor antagonist with psychotogenic and cognitive effects in healthy volunteers and schizophrenic patients which has been proposed to be a useful tool to investigate neurobiological basis of schizophrenia. OBJECTIVE: The present study characterized the effects of a subanesthetic dose of ketamine on memory and related subjective states of awareness in healthy volunteers. METHODS: Twenty-six subjects were given either a 60-min ketamine (0.5 mg/kg per hour) or a placebo infusion. To obtain constant plasma ketamine throughout the experiment, ketamine was administered using a computer-controlled infusion system. Subjects carried out episodic memory tasks involving words presented before and during infusion. Memory performance was assessed with recognition and free recall tasks. Subjective states of awareness were assessed using an experiential approach. Levels of psychopathology were evaluated with BPRS. RESULTS: Ketamine impaired performance in free recall and recognition of words presented during, but not before, infusion. There were no differences between groups concerning states of awareness associated with recognition memory. Subjects under ketamine had higher BPRS total scores as well as BPRS negative and positive cluster scores than control subjects. CONCLUSIONS: Ketamine decreases episodic memory performance by impairing encoding, but not retrieval processes. It does not selectively impair subjective states of awareness associated with recognition memory as it has been seen in patients with schizophrenia. Ketamine might mimic the memory impairment associated with acute, but not chronic, forms of schizophrenia.

Lorazepam impairs both visual and auditory perceptual priming.

RATIONALE: Lorazepam has been repeatedly shown to impair both explicit memory and perceptual priming, a form of implicit memory, in the visual domain. However, the effects of this benzodiazepine on priming in other perceptual domains, such as auditory priming, have never been explored. OBJECTIVE: The present study investigated whether the deleterious effects of lorazepam on perceptual priming are restricted to the visual domain, or if they could be extended to the auditory domain. METHODS: Thirty-two healthy volunteers were randomly assigned to two parallel groups, placebo and lorazepam 0.038 mg/kg. The drug was administered orally, following a double-blind procedure. In the same subjects, perceptual priming was assessed in the auditory and visual domains using similar word-stem completion tasks, and explicit memory was explored using a free-recall task. RESULTS: Lorazepam markedly reduced free-recall performance for visually and auditorily presented words. Lorazepam equally impaired visual and auditory priming. In the auditory word-stem completion task, prior presentation of a word facilitated perception of its stem in the placebo group. This facilitation effect was not observed in the lorazepam group. The lorazepam-induced impairment of priming was not due to sedation or explicit contamination. CONCLUSION: These results indicate that the deleterious effects of lorazepam on priming are not restricted to the visual modality, but extend to the auditory modality.

Diazepam induces a dissociation between explicit and implicit memory.

The effects of 0.2 mg/kg orally administered diazepam and of a placebo on explicit memory, implicit and knowledge memory were assessed using a free recall task, a word-stem completion task and two category-generation tasks. Twenty four healthy volunteers took part in this double-blind study. Diazepam impaired explicit but not implicit memory. The drug also spared knowledge memory. Explicit memory was linked with the diazepam-induced sedation and with the self-rated affective load of to-be remembered words, but implicit memory was not. The diazepam-induced dissociation between explicit and implicit memory supports the notion of two distinct forms of memory and reproduced the dissociation observed in organic amnesia.