Effet de l’écoute de mots déjà hallucinés chez des sujets schizophrènes en remission: étude de six cas par la résonance magnétique nucléaire fonctionnelle

L'hypothèse d'un discours intérieur non reconnu comme sien par le sujet halluciné et l'hypothèse d'une activité aberrante de l'aire auditive primaire demeurent les deux hypothèses les plus étudiées actuellement afin d'expliquer la genèse des hallucinations auditives. Dans la plupart des cas, le contenu verbal des hallucinations auditives demeure le même d'un épisode psychotique à l'autre même si les deux épisodes sont séparés par une longue période de rémission. De plus, ce contenu est souvent réactivé lors de situations stressantes pour le sujet atteint. Nous émettons l'hypothèse que le contenu verbal des hallucinations auditives demeure présent à un niveau infra-clinique, même durant les périodes de rémission totale, et que l'écoute d'un tel contenu active les régions cérébrales impliquées dans le traitement cognitif des hallucinations. Dans cette étude, nous avons utilisé, chez des sujets schizophrènes, l'imagerie par résonance magnétique fonctionnelle (IRMF) afin d'identifier les régions cérébrales associées au traitement de mots déjà entendus par ces sujets au cours de leurs hallucinations auditives. Les sujets schizophrènes devaient être en rémission totale des hallucinations auditives depuis au moins une année. Des sujets sains ont été imagés tandis qu'ils entendaient les mêmes mots. Les résultats ont révélé que l'écoute du contenu hallucinatoire s'accompagne d'une activation essentiellement localisée au niveau de la région orbitofrontale/préfrontale médiane chez les sujets schizophrènes mais pas chez les sujets témoins. Nous en concluons que les mots hallucinés produisent des changements hémodynamiques au niveau cérébral même en période de rémission totale relativement aux hallucinations auditives. La région orbitofrontale/préfrontale médiane serait un site important pour le traitement des mots hallucinés. Un dérèglement de cette région, habituellement impliquée dans le traitement des émotions, conduirait à l'association inappropriée d'une émotion particulière aux mots hallucinés. De cette façon, même des mots neutres sur le plan affectif deviendraient chargés émotionnellement, retenant l'attention du sujet halluciné et biaisant ses perceptions auditives. Despite immense importance of auditory verbal hallucinations (AVHs) in the phenomenology of schizophrenia, the neurocognitive and neurophysiological bases of AVHs remain obscure. On the neurocognitive level, it has been proposed that AVHs arise from the disordered monitoring manifested by patients' inability to recognize their inner speech as being their own. On the neurophysiological level, the AVHs have been attributed to the aberrant activity in the primary auditory cortex (Heschl's gyrus). Although interesting, these models cannot account for the very specific and restricted content of AVHs in individual patients. The specific content of AVHs persists across different psychotic episodes even after extended periods of remission. Furthermore, the AVHs are usually triggered by emotionally charged and stressful situations. We hypothesized that even during absence of AVHs, when patients are in remission, the verbal content remains present in the latent, pre-clinical form. In order to elucidate potential cerebral substrates of the dormant AVHs content, we employed functional magnetic resonance imaging (fMRI) in 6 schizophrenia patients in total remission of AVHs for at least 12 months, during listening to the words hallucinated by them in the past. Specifically, we created the list of previously hallucinated words for each patient and matched the words in terms of length, structure, emotional valence, semantic category and frequency of usage with the non-hallucinated words. Moreover, each patient was paired demographically with the control participant who was presented with the same words. We predicted that exposure to the hallucinated versus non-hallucinated words would result in increased activation in cerebral areas associated with cognitive and emotional content of previously experienced AVHs in patients, whereas the same comparison will not produce any significant changes in blood oxygen level-dependent (BOLD) signal in control participants. In addition, based on existing neuroimaging data obtained during experience of AVHs, we hypothesized that previously hallucinated words may elicit greater activation in the primary auditory cortex than the non-hallucinated words in patients. Each pair of participants was analyzed separately. The most consistent finding in patients, absent in all control participants, was significant activation in the orbitofrontal and medial prefrontal cortex (PFC) during listening to previously hallucinated versus non-hallucinated words. The orbitofrontal and medial PFC are both part of corticolimbic system and play an important role in cognitive control of emotion processing. Thus, present results imply that previously hallucinated words, even in remission, are associated with inappropriate emotional response on neurophysiological level in schizophrenia patients. The relative hyperactivation of orbitofrontal and medial PFC in patients may stem from and/or may contribute to anomalous neural plasticity and disordered connectivity in the corticolimbic circuitry. This in turn could lead to attribution of excessive emotional salience to normally neutral stimuli and over time via process of sensitization could result in hallucinations. Potential normalization of this dysfunction could reduce patients' susceptibility to experience AVHs in stressful situations. In addition to observed hyperactivations in the PFC, some schizophrenia patients exhibited anomalous BOLD signal in other regions of the corticolimbic system such as anterior cingulate gyrus and parahippocampal gyrus. These additional anomalies could be related to greater affective sensitivity to the hallucinated versus non-hallucinated words in some patients. Finally, in contrast to our initial hypothesis we did not observe any significant differences between processing of the hallucinated versus non-hallucinated words in the primary auditory cortex. In retrospect, this result is not surprising because patients did not experience internally generated AVHs while in the scanner, but instead were exposed exclusively to externally generated stimuli.