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Biomedical subjects

J M Danion

Publications and source records attributed to J M Danion.

At least 19 recordsLinked to original sources
PubMed2002

Lorazepam, sedation, and conscious recollection: a dose-response study with healthy volunteers.

The role of sedation in the benzodiazepine-induced impairment of conscious recollection is still subject to debate. The aim of this study was to investigate further the role of sedation using the Remember-Know procedure and a physiological measure of sedation based on pupillography in addition to standard measures of sedation and attention (digit-symbol substitution task, symbol cancellation task, self-rated sedation). Twelve subjects were tested after the intake of placebo, lorazepam 0.026 mg/kg and lorazepam 0.038 mg/kg, administered in a randomized order, with a minimum interval of 8 days between each administration. On a recognition memory task, 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. Lorazepam selectively impaired recognition based on 'Remember' responses. This impairment was greater in the lorazepam 0.038 mg/kg than in the lorazepam 0.026 mg/kg groups. Measures of sedation were not correlated with the proportion of 'Remember' responses. These results suggest that sedation alone cannot account for the impairment of conscious recollection induced by lorazepam.

Adult↗
PubMed2001

Consciousness in schizophrenia: a metacognitive approach to semantic memory.

Recent studies have shown that schizophrenia may be a disease affecting the states of consciousness. The present study is aimed at investigating metamemory, i.e., the knowledge about one's own memory capabilities, in patients with schizophrenia. The accuracy of the Confidence level (CL) in the correctness of the answers provided during a recall phase, and the predictability of the Feeling of Knowing (FOK) when recall fails were measured using a task consisting of general information questions and assessing semantic memory. Nineteen outpatients were paired with 19 control subjects with respect to age, sex, and education. Results showed that patients with schizophrenia exhibited an impaired semantic memory. CL ratings as well as CL and FOK accuracy were not significantly different in the schizophrenic and the control groups. However, FOK ratings were significantly reduced for the patient group, and discordant FOK judgments were also observed more frequently. Such results suggest that FOK judgments are impaired in patients with schizophrenia, which confirms that schizophrenia is an illness characterized by an impaired conscious awareness of one's own knowledge.

Adult↗
PubMed2001

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.

Adolescent↗
PubMed2001

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.

Adult↗
PubMed2001

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.

Adult↗
PubMed2001

Effects of lorazepam on vision and oculomotor balance.

BACKGROUND: Previous studies have shown an effect of the tranquilizer lorazepam on visual perception. We explored the effects of the drug on binocular vision, visual acuity and accommodation. SUBJECTS AND METHODS: Twenty-four paid healthy volunteers (13 women, 11 men) were recruited from the University of Strasbourg (mean age: 23.6 years, mean weight: 66.8 Kg). They were randomly assigned to one of two parallel groups of 12 subjects each (a placebo group and a lorazepam 0.038 mg/kg group). Visual acuity was measured for each eye separately (Snellen chart and Parinaud scale). Binocular vision was studied using the cover tests, measurement of the fusional amplitudes (with Berens prisms), and the Duane Scale Test (near point rule) measuring convergence and/or accommodation in centimeters or diopters as a function of age. RESULTS: Regarding vision, there was no lorazepam effect, at either 33 cm or 5 m. An esophoria was observed after the intake of lorazepam (0Delta before intake and 2.8Delta after intake, p=0.001). Both fusional convergence and fusional divergence amplitudes decreased by lorazepam, (p=0.008, and p=0.002). Lorazepam also impaired the near point of convergence but did not affect accommodation. CONCLUSION: A single dose of lorazepam induces an esophoric oculomotor imbalance and impaired fusional convergence and divergence amplitudes without impairing visual acuity or accommodation.

Accommodation, Ocular↗
PubMed2000

Reduction of latent inhibition by D-amphetamine in a conditioned suppression paradigm in humans.

The sensitivity of latent inhibition (LI) to amphetamine has been tested in humans with a paradigm close to the conditioned emotional response suppression currently used in experimental animals. The conditioned stimulus (CS) was a tone, the unconditioned stimulus (US) a strong white noise, and the response a transient delay in a regular sequence of hand movements in the resolution of the Tower of Toronto puzzle. The aim of this study was to verify whether the previously reported, disruptive effect of CS preexposure on conditioning really represents LI, by examining its sensitivity to amphetamine. Three groups of healthy volunteers received placebo, 5 or 10 mg of dexamphetamine sulphate, respectively, in a double-blind experimental design. The preexposure, conditioning and test phases were carried out under either amphetamine or placebo. The non preexposed groups treated with amphetamine were not different from the non preexposed placebo group, indicating that amphetamine did not affect conditioning. Among the preexposed groups, those receiving 10 mg of amphetamine showed normal rates of conditioning, whereas those treated with either 5 mg of amphetamine or placebo showed LI. Similar results have been reported in experimental animals. This sensitivity to amphetamine suggests that the present paradigm may be used to study LI in humans.

Acoustic Stimulation↗
PubMed2000

Associative learning and latent inhibition in a conditioned suppression paradigm in humans.

A paradigm based on conditioned suppression of ongoing motor activity, sensitive to latent inhibition (LI), was developed and tested in healthy volunteers. Subjects were trained to move disks from one peg to another with a high degree of regularity in the Tower of Toronto puzzle, a well-known cognitive skill learning task. Once this was achieved, they were submitted to a Pavlovian conditioning procedure. The conditioned stimulus (CS) was a pure tone and the unconditioned stimulus (US) a loud white noise. The resulting response suppression was assessed by a transient increase in latency of the hand movements. In control subjects, there was non-contingent CS and US presentation. The results evidenced conditioning after a single CS-US pairing. Following five preexposures to the to-be-conditioned CS, however, conditioning was abolished, seemingly expressing LI. Because a weak unconditioned response to the tone was observed after its first two presentations, an additional experiment was performed with two preexposures to the to-be-conditioned CS. With such procedure, conditioning was obtained, supporting the existence of LI in the preceding experiment. These results indicate that the present paradigm may be useful for the study of LI in human subjects, having the advantage of being similar to the experimental conditions used in the majority of LI studies in experimental animals.

Acoustic Stimulation↗
PubMed2000

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.

Adult↗
PubMed2000

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.

Adult↗
PubMed1999

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.

Adult↗
PubMed1999

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.

Adult↗
PubMed1999

What is the nature of increased Stroop interference in schizophrenia?

In comparison to controls, patients with schizophrenia classically display (1) an overall slowing in response times (RTs) and (2) a disproportionate slowing in RTs in the conflict condition of the Stroop color/word interference task. These two effects appear repeatedly in the card version of the Stroop task but were not replicated in a number of studies using a computer item-by-item version of the task. The present study was aimed at understanding the exact nature of the increased interference classically found in the performance of patients with schizophrenia in the card version of the Stroop task. We used a computer trial-by-trial version in which we investigated the effects of two major methodological differences between the two versions: (1) blocked (card version) versus mixed (computer version) presentation of the neutral, congruent and conflict conditions and (2) presence (card version) versus absence (computer version) of distractors in the spatial surrounding of the target. We found an overall slowing in performance and a disproportionate slowing in the conflict condition for patients with schizophrenia but only when the target was surrounded by distractors (in Experiments 2 and 3). The data are discussed in terms of a deficit in selective attention and inhibitory processes in schizophrenia.

Adult↗
PubMed1999

Impairment of consciously controlled use of memory in schizophrenia.

Recent studies of memory in schizophrenia have shown that explicit but not implicit memory performance is impaired. The hypothesis that schizophrenia is associated with a failure of consciously but not unconsciously (automatic) controlled influence of memory on performance was tested using a procedure providing uncontaminated estimates of consciously controlled and automatic memory processes (i.e., the process-dissociation procedure in a stem completion task). Performance of 35 patients with schizophrenia was compared with that of 35 normal participants. Consciously controlled use but not automatic influences of memory was significantly lower in patients with schizophrenia than in controls. Consciously controlled use of memory was negatively and significantly correlated with positive symptoms of schizophrenia. Schizophrenia differentially affects 2 types of memory processes: It impairs consciously controlled use of memory but spares automatic influences. Positive symptoms could reflect the lack of control from higher level conscious processes.

Adult↗
PubMed1999

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.

Adolescent↗
PubMed1998

Initiation and supervisory processes in schizophrenia and depression.

Clinical studies show that schizophrenic and depressive subjects have problems with daily life activities, and neuropsychological studies tend to explain these problems in terms of a dysexecutive syndrome. Verbal fluency and sentence arrangement are tasks considered to focus on two aspects of the dysexecutive syndrome known as initiation and supervision processes, respectively. In this study, we assessed performance in these two tasks in schizophrenia and depression. Twenty-six schizophrenic subjects (chronic schizophrenia, DSM IV definition) were compared with 26 control subjects balanced for sex, age and educational level, and 16 depressive subjects (major depression episode, DSM IV) were compared with 11 similarly balanced control subjects. Switching and clustering scores were evaluated during a semantic fluency task as two components underlying the initiation and organization processes. Capture errors specific to failure of the supervisory system and differences between the number of correct responses in two conditions (valid/invalid) were evaluated as indexes of the supervision process in a sentence arrangement task. In the semantic fluency task, switching scores were significantly lower in the schizophrenic and depressive subjects than in their respective controls. In the sentence arrangement task, only the schizophrenic subjects made significantly more capture errors than their controls and had significantly fewer correct sequences in invalid conditions than in valid conditions. This study shows a dissociation between supervision and initiation processes in two different psychiatric populations. Initiation is impaired, but supervision is preserved in depression, whereas both initiation and supervision are impaired in schizophrenia.

Adult↗
PubMed1998

The state of functioning of working memory in schizophrenia.

The functioning of working memory in schizophrenic patients according to Baddeley's model was examined in two complementary experiments. Experiment 1 comprised 27 patients and their controls, matched in age and level of education. Of this pool, 20 pairs participated also in Experiment 2. Digit span, reading rate, and immediate serial recall assessed the functioning of the phonological loop. Corsi and pattern span tasks assessed the capacity of visuo-spatial memory. The central executive's ability to monitor two concurrent tasks was evaluated in a dual task paradigm, and its capacity to control action in a random generation task. A preliminary set of analyses showed that the patients' performances were reduced in all tasks explored, except in digit span. This initial pattern changed consistently after controlling for reading rate. While slow and fast reading patients were comparable in demographic and clinical criteria, slow reading patients showed impaired performance in all tasks, whereas fast reading patients exhibited reduced performance in visuo-spatial tasks and in the random generation task only. The state of functioning of working memory in schizophrenia appears, therefore, to vary consistently among the components of the model and is markedly impaired in slow reading patients. The implications of slowness are discussed.

Adult↗