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In schizophrenia patients, glutathione dysregulation at the gene, protein and functional levels, leads to N -methyl- D -aspartate (NMDA) receptor hypofunction. These patients also exhibit deficits in auditory sensory processing that manifests as impaired mismatch negativity (MMN), which is an auditory evoked potential (AEP) component related to NMDA receptor function. N -acetyl-cysteine (NAC), a glutathione precursor, was administered to patients to determine whether increased levels of brain glutathione would improve MMN and by extension NMDA function. A randomized, double-blind, cross-over protocol was conducted, entailing the administration of NAC (2g/day) for 60 days and then placebo for another 60 days (or vice versa). 128-channel AEPs were recorded during a frequency oddball discrimination task at protocol onset, at the point of cross-over, and at the end of the study. At the onset of the protocol, the MMN of patients was significantly impaired compared to sex- and age- matched healthy controls ( p =0.003), without any evidence of concomitant P300 component deficits. Treatment with NAC significantly improved MMN generation compared with placebo ( p =0.025) without any measurable effects on the P300 component. MMN improvement was observed in the absence of robust changes in assessments of clinical severity, though the latter was observed in a larger and more prolonged clinical study. This pattern suggests that MMN enhancement may precede changes to indices of clinical severity, highlighting the possible utility AEPs as a biomarker of treatment efficacy. The improvement of this functional marker may indicate an important pathway towards new therapeutic strategies that target glutathione dysregulation in schizophrenia.

La remédiation cognitive est devenue en quelques années un outil thérapeutique important dans le domaine des maladies psychiatriques, et plus particulièrement dans celui des troubles schizophréniques. Parmi les programmes utilisés, RECOS est l’un des seuls à proposer un entraînement qui tient compte du profil cognitif individuel, permettant ainsi de répondre de manière ciblée à la grande hétérogénéité des déficits observés. Cet ouvrage constitue le support de base indispensable à la formation délivrée aux futurs thé-rapeutes RECOS. Il se divise en deux parties. La première partie présente les données scien-tifiques actuelles sur les troubles cognitifs de la schizophrénie et les moyens d’y remédier. Le lien entre les performances cognitives et les capacités fonctionnelles permet de comprendre comment et pourquoi la remédiation cognitive favorise la réinsertion sociale et profession-nelle. La deuxième partie fait office de manuel d’utilisation pour tous les thérapeutes (psy-chologues, psychiatres, infirmiers, ergothérapeutes) souhaitant utiliser RECOS. L’ouvrage décrit les pathologies psychiatriques visées par le programme, la schizophrénie n’étant pas la seule concernée. Il aborde ensuite les différentes étapes du traitement, en consacrant une place importante à l’évaluation cognitive et clinique ainsi qu’aux exercices de remédiation. Des cas cliniques illustrent la manière d’adapter le travail thérapeutique au profil cognitif de chaque participant. Afin que le lecteur puisse bénéficier d’un maximum d’informations et de documents pratiques, plusieurs outils nécessaires à l’utilisation du programme figurent en annexe de l’ouvrage.

We studied top-down visual processes in schizophrenia by analyzing visual event-related potentials (ERPs) during a gestalt recognition task, after subjects (patients with schizophrenia, n = 10; controls, n = 14) were trained to perceive three different geometrical shapes. Recognition performance of patients was poorer under both the figure and the nonfigure conditions then that of normal controls. ERPs analysis indicated that P300 amplitudes of the patients were significantly smaller than those of controls during correct figure detection trials. Moreover, topographical analysis of the differences in ERPs during the figure vs the nonfigure condition showed an earlier, more positive and more widely distributed P300 in controls than in patients with schizophrenia. Our study supports the misconnection hypothesis of schizophrenia and highlights the difficulty of the patients to refer to previous experience in order to filter incoming information. In a visual recognition task, this misconnection syndrome might induce a failure to integrate information stored in the frontal and prefrontal sites with incoming stimuli.

Higher cognitive processes include the ability to reliably transform sensory or mnemonic information. These processes either occur automatically or they are consciously controlled. To compare these two types of information processing, we developed a reaction time task that requires either a rule operation or else a direct sensory association. We were interested in evaluating the brain's electrical activity corresponding to both tasks, using event-related potentials (ERPs). In order to gain complete insight into the electrical activity of a stimulus-response segment, we analyzed the ERPs corresponding to the processing of the stimulus and the ERPs corresponding to the preparation of the response. To complete the analysis, we also evaluated the lateralized readiness potential (LRP) matched to the stimulus and to the response onset. Compared with the sensory association task, rule operation generated a higher negative potential field at frontocentral scalp areas in a latency range of 312-512 ms after the stimulus. In contrast, the LRP showed a negative component in the sensory association task which was absent during the rule operation; the latency of the difference was in the range 374-532 ms after the stimulus. The ERP component obtained by the response onset analysis was more negative in the rule condition up to a latency of -214 ms before the generation of the movement; the effect was localized at frontal and central scalp regions. We failed to find any significant difference in the LRP matched to the response onset. These results suggest that the brain computation of the rule operation takes place approximately in the middle of the stimulus-response time interval and that it is an additive process to the sensory association response.