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.

Effects of lorazepam and diazepam on conscious and automatic memory processes.

Recent studies exploring benzodiazepine memory effects have used the distinction between explicit and implicit tasks. There is now increasing evidence that implicit tasks can be "contaminated" by conscious uses of memory and that unconscious (automatic) use of memory can contaminate explicit tasks, leading to mistaken estimates of their respective influences on memory performance. The aim of the present double-blind, double-placebo study was to assess the memory effects of diazepam and lorazepam using a process-dissociation procedure in a stem-completion task, this procedure providing uncontaminated estimates of conscious and automatic memory processes. The memory task was administrated to 60 healthy volunteers randomly assigned to one of three parallel groups (placebo, diazepam 0.3 mg/kg, lorazepam 0.038 mg/kg). Lorazepam markedly reduced conscious as well as automatic influences of memory. Diazepam also reduced conscious uses of memory, albeit to a lesser extent than lorazepam, but did not decrease the influence of automatic memory. Secondary analyses showed that when the deleterious effect on conscious uses of memory was equated between a diazepam subgroup and the lorazepam group, only lorazepam impaired the automatic use of memory. This study strongly suggests a qualitative difference in the memory effects of the two benzodiazepines. It has some implications regarding the relationships between states of consciousness and memory processes.

Effects of haloperidol and amisulpride on motor and cognitive skill learning in healthy volunteers.

The effects of a typical neuroleptic, haloperidol (1 and 2 mg orally), of an atypical neuroleptic, amisulpride (50 and 100 mg) and of a placebo on motor and cognitive skill learning were assessed in 60 healthy volunteers using repeated testing on the Tower of Toronto puzzle. Subjects were asked to solve three blocks of eight trials and, at distance from drug administration, a fourth block. The puzzle was connected to a computer in order to obtain a precise timing of individual moves. Two components of cognitive skill learning were assessed, the ability to learn to solve the puzzle and the acquisition of a problem-solving routine. Subjective feelings of effort and automatisation of the task were assessed using a questionnaire. Like placebo-treated subjects, neuroleptic-treated subjects were able to acquire a motor skill, to learn to solve the puzzle and to acquire a routine. However, haloperidol 2 mg-treated subjects needed significantly more moves to solve the puzzle in blocks 3 and 4, some of them having routinised a non-optimal solution. A significant cognitive slowing was observed in the haloperidol 1 mg group in block 4. The performance pattern and verbal reports suggested that haloperidol impaired the higher cognitive functions such as the ability to shift from one strategy to another and/or to assess one's performance accurately, possibly leading to the development of compensatory strategies. The only deleterious amisulpride effect was a cognitive slowing in block 4, which was observed in the lower dose group.

Lorazepam and diazepam effects on memory acquisition in priming tasks.

Unlike diazepam, lorazepam has repeatedly been shown to impair perceptual priming as well as explicit memory. To determine whether this deleterious effect was due to an impairment in acquisition of information, 60 healthy volunteers were randomly assigned to five treatment groups (placebo, lorazepam 0.026 or 0.038 mg/kg, diazepam 0.2 or 0.3 mg/kg) and successively performed perceptual priming tasks and a free-recall task. Priming performance on information learned before or 2 h after drug administration, i.e. at the peak concentration of lorazepam, was assessed under the influence of the drugs, using a picture-fragment and a word-stem completion task. Free-recall performance was altered by both drugs. Lorazepam decreased priming performance when information was acquired after, but not before, drug administration, indicating that the drug alters the acquisition of information. Lorazepam also impaired the ability to identify fragmented pictures, but there was no evidence that this perceptual effect accounts for the priming impairment. Surprisingly, diazepam also decreased priming when information was acquired after drug administration, suggesting that, at least in certain circumstances, the two benzodiazepines may exert similar effects on priming measures.

Differential effects of diazepam and lorazepam on repetition priming in healthy volunteers.

The effects of two benzodiazepines, diazepam (15 or 20 mg orally) and lorazepam (1.75 or 2.5 mg orally), and a placebo on explicit memory, lexical priming and perceptual priming were assessed using a free-recall, a word-completion and a picture-completion test. The picture-completion test included two different study conditions intended to manipulate the magnitude of the priming effect. Sixty healthy volunteers took part in this double-blind study. Free-recall performances were altered by both drugs. Lorazepam impaired word-completion and picture-completion performance, whereas diazepam only exhibited a deleterious effect on the more sensitive of the two measures of the picture-completion test. These results indicate that the two benzodiazepines have differential amnestic effects. It is suggested that these differential effects could be accounted for by a different cortical distribution of the two benzodiazepines.

Confidence level and feeling of knowing for episodic and semantic memory: an investigation of lorazepam effects on metamemory.

The effects of lorazepam (0.026 or 0.038 mg/kg), a benzodiazepine, and of a placebo on metamemory, i.e. knowledge about one's own memory capabilities, were investigated in 36 healthy volunteers. Accuracy of confidence levels (CL) in the correctness of recalled answers and accuracy of feeling of knowing (FOK) the answers when recall fails were measured using a sentence memory task assessing episodic memory and a task consisting of general information questions and assessing semantic memory. Lorazepam impaired episodic memory. Unexpectedly, it also impaired performance in both the recall and recognition phases of the task assessing semantic memory, suggesting that it decreased the ability to distinguish between correct and incorrect information. In episodic memory, lorazepam 0.038 mg/kg-treated subjects exhibited an impaired CL accuracy, compared to placebo-treated subjects, and their FOK accuracy was at chance. In semantic memory, their overall CL and FOK accuracy was apparently spared. However, these subjects selectively overestimated their CL judgements for incorrect answers; moreover, secondary analyses showed that FOK accuracy for a subset of low-accuracy items was virtually nil. These results suggest that lorazepam impairs metamemory for both episodic and semantic memory.

Affective valence of words, explicit and implicit memory in clinical depression.

Explicit and implicit memory for affectively valenced words (positive, negative or neutral) were investigated in 30 patients suffering from a major depressive episode (DSM-III-R criteria) and 30 normal control subjects. Explicit memory was assessed with a free-recall and a recognition task and implicit memory with a word-stem completion task. Depressed and control subjects recalled more emotional, i.e., positive and negative, words than neutral ones. They recognized less negative than neutral words. In contrast, to recall and recognition performance, word-completion performance was not sensitive to the affective valence of words: depressed and control subjects exhibited equivalent priming of positive, negative and neutral words. These results indicate that, in depressed and normal subjects, the affective valence of words influences memory when conscious, intentional recollection is required but is devoid of effect when such a recollection is not required.

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.

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.