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Eichenlaub J.-B.,Lyon Neuroscience Research Center | Eichenlaub J.-B.,University Claude Bernard Lyon 1 | Nicolas A.,Center Hospitalier le Vinatier | Daltrozzo J.,Lyon Neuroscience Research Center | And 5 more authors.
Neuropsychopharmacology | Year: 2014

Dreaming is still poorly understood. Notably, its cerebral underpinning remains unclear. Neuropsychological studies have shown that lesions in the temporoparietal junction (TPJ) and/or the white matter of the medial prefrontal cortex (MPFC) lead to the global cessation of dream reports, suggesting that these regions of the default mode network have key roles in the dreaming process (forebrain 'dream-on' hypothesis). To test this hypothesis, we measured regional cerebral blood flow (rCBF) using 15 OH 2 O positron emission tomography in healthy subjects with high and low dream recall frequencies (DRFs) during wakefulness (rest) and sleep (rapid eye movement (REM) sleep, N2, and N3). Compared with Low recallers (0.5±0.3 dream recall per week in average), High recallers (5.2±1.4) showed higher rCBF in the TPJ during REM sleep, N3, and wakefulness, and in the MPFC during REM sleep and wakefulness. We demonstrate that the resting states of High recallers and Low recallers differ during sleep and wakefulness. It coheres with previous ERP results and confirms that a high/low DRF is associated with a specific functional organization of the brain. These results support the forebrain 'dream-on' hypothesis and suggest that TPJ and MPFC are not only involved in dream recall during wakefulness but also have a role in dreaming during sleep (production and/or encoding). Increased activity in the TPJ and MPFC might promote the mental imagery and/or memory encoding of dreams. Notably, increased activity in TPJ might facilitate attention orienting toward external stimuli and promote intrasleep wakefulness, facilitating the encoding of the dreams in memory. © 2014 American College of Neuropsychopharmacology.


Poulin H.,University of Quebec | Bruhova I.,State University of New York at Buffalo | Timour Q.,University of Lyon | Theriault O.,University of Quebec | And 5 more authors.
Molecular Pharmacology | Year: 2014

The voltage-gated Nav1.5 channel is essential for the propagation of action potentials in the heart. Malfunctions of this channel are known to cause hereditary diseases. It is a prime target for class 1 antiarrhythmic drugs and a number of antidepressants. Our study investigated the Nav1.5 blocking properties of fluoxetine, a selective serotonin reuptake inhibitor. Nav1.5 channels were expressed in HEK-293 cells, and Na+currents were recorded sing the patch-clamp technique. Dose-response curves of racemic fluoxetine (IC50=39 μM) and its optical isomers had a similar IC50[40 and 47 μM for the (+) and (-) isomers, respectively]. Norfluoxetine, a fluoxetine metabolite, had a higher affinity than fluoxetine, with an IC50of 29 μM. Fluoxetine inhibited currents in a frequency-dependent manner, shifted steady-state inactivation to more hyperpolarized potentials, and slowed the recovery of Nav1.5 from inactivation. Mutating a phenylalanine (F1760) and a tyrosine (Y1767) in the S6 segment of domain (D) IV (DIVS6) significantly reduced the affinity of fluoxetine and its frequency-dependent inhibition. We used a noninactivating Nav1.5 mutant to show that fluoxetine displays open-channel block behavior. The molecular model of fluoxetine in Nav1.5 was in agreement with mutational experiments in which F1760 and Y1767 were found to be the key residues in binding fluoxetine. We concluded that fluoxetine blocks Nav1.5 by binding to the class 1 antiarrhythmic site. The blocking of cardiac Na+ channels should be taken into consideration when prescribing fluoxetine alone or in association with other drugs that may be cardiotoxic or for patients with conduction disorders. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.


Kaliuzhna M.,University of Lyon | Kaliuzhna M.,Ecole Polytechnique Federale de Lausanne | Chambon V.,University of Lyon | Franck N.,University of Lyon | And 3 more authors.
PLoS ONE | Year: 2012

The dominant cognitive model that accounts for the persistence of delusional beliefs in schizophrenia postulates that patients suffer from a general deficit in belief revision. It is generally assumed that this deficit is a consequence of impaired reasoning skills. However, the possibility that such inflexibility affects the entire system of a patient's beliefs has rarely been empirically tested. Using delusion-neutral material in a well-documented advice-taking task, the present study reports that patients with schizophrenia: 1) revise their beliefs, 2) take into account socially provided information to do so, 3) are not overconfident about their judgments, and 4) show less egocentric advice-discounting than controls. This study thus shows that delusional patients' difficulty in revising beliefs is more selective than had been previously assumed. The specificities of the task and the implications for a theory of delusion formation are discussed. © 2012 Kaliuzhna et al.


Franck N.,Center Hospitalier le Vinatier
Journal de Therapie Comportementale et Cognitive | Year: 2012

Cognitive disorders (memory, attention, executive functions, metacognition and social cognition disorders) are frequently associated with chronic psychoses particularly schizophrenia. These cognitive disorders greatly compromise the ability of afflicted patients to care for themselves and also significantly affect their social functioning. Furthermore, they manifest with the first psychotic episode. While these symptoms are not as obvious as the defining psychotic symptoms (e.g., hallucinations and delusions), their behavioral consequences can be just as detrimental. Social interactions, work, and leisure activities can all involve basic cognitive activities such as repeating a phone number, integrating interlocutor speech, or organizing one's own behavior towards defined goals; all the while having to take context into account. The persistence of criticizing delusions or stabilization of verbal hallucinations through treatment are frequently less incapacitating than even moderate cognitive dysfunction. The nature of the cognitive deficit, as revealed by the neuropsychological assessment, can identify the type of functional impairment in a given patient. Deficits in attention and working memory can result in an alteration of occupational functioning. Executive function disorders have an impact on behavior in relationships. Processing speed, attention span and working memory all have an impact on social skills. Cognitive impairment is not necessarily directly linked to functional disability, yet its effects may mediated by other variables such as a patient's ability to manage a variety of tasks: daily life, social skills, social cognition performances, symptoms, intrinsic motivation and metacognition. Although functional disability is greater for schizophrenia than for bipolar disorder, cognitive impairments are predictive of overall disability for both disorders. Antipsychotics have little beneficial effect on cognitive disorders. While they certainly can alleviate secondary cognitive deficits (e.g., attention disorder resulting from an intense hallucinatory activity), they may also generate iatrogenic cognitive impairments. Cognitive side effects are even more consequential given that antipsychotics are not systematically prescribed with the minimum effective dose; cognitive side effects may be present even in low dosage of antipsychotics when the drug has additional antihistamine or anticholergentic effects. Iatrogenic effects can be aggravated if an antiparkinsonian or a benzodiazepine corrector is associated because of their adverse effects on attention and, additionally, adverse effects on memory abilities for drugs with anticholinergic or GABAergic action. Cognitive remediation was developed to reduce the cognitive deficits or compensate for their consequences by developing alternative skills. The goal of cognitive remediation is concrete intending to promote a professional or social reintegration focusing on an intermediate variable that constitutes itself cognitive performance. To achieve this goal, cognitive remediation targets attention, memory, language and executive processes, as well as social cognition disorders. Improving performances in these areas appears to have a positive impact on functional deficits that affect daily life. Cognitive remediation is not an alternative to psychotropic treatments and/or psychotherapy, but is intended to supplement their effects. These three methods of treatment act at different levels. In practice, cognitive remediation provides an improvement in cognitive functioning, either directly by retraining the impaired functions, or indirectly through the functions developed in order to compensate. Taking into account the patient's vulnerability aids in reducing his handicap and encouraging recovery, through validation of the various situations he or she faces in daily life. Cognitive remediation is an essential therapeutic tool that can promote psychosocial rehabilitation in a patient with chronic psychotic disorder. Ideally it should be associated with other rehabilitating tools, like social skills training, psychoeducation, role playing (using a non-threatening situation), and family support. Cognitive remediation is indicated for patients whose clinical condition is stable and for whom medication is reduced to the minimum effective dose. In the ideal scenario, it is advisable to treat only the primary symptoms linked to cognitive disorders (rather than the secondary ones) or iatrogenic cognitive impairments. In some cases, the patients under care of are still symptomatic or suffering from iatrogenic cognitive effects. Should some symptoms remain under antipsychotic medication, cognitive remediation is fully justified when the benefit-risk ratio has been clearly determined. It is, however, necessary that patient condition remain stable and that some practical benefits can be attained. © 2012 Association française de thérapie comportementale et cognitive.


Harle B.,Center Hospitalier le Vinatier | Desmurget M.,French National Center for Scientific Research
Archives de Pediatrie | Year: 2012

During the last few years, the time spent in front of various screens, including TV sets, video games, smartphones and computers, has dramatically increased. Numerous studies show, with a remarkable consistency, that this trend has a strong negative influence on the cognitive development of children and teenagers. The affected fields include, in particular, scholastic achievement, language, attention, sleep and aggression. We believe that this often disregarded - not to say denied - problem should now be considered a major public health issue. Primary care physicians should inform parents and children about this issue to support efficient prevention. © 2012 Elsevier Masson SAS.

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