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Détection Automatisée Des Hallucinations Auditives En IRM Fonctionnelle Et Perspectives Thérapeutiques Dans La Schizophrénie Thomas Fovet

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Détection Automatisée Des Hallucinations Auditives En IRM Fonctionnelle Et Perspectives Thérapeutiques Dans La Schizophrénie Thomas Fovet Détection automatisée des hallucinations auditives en IRM fonctionnelle et perspectives thérapeutiques dans la schizophrénie Thomas Fovet To cite this version: Thomas Fovet. Détection automatisée des hallucinations auditives en IRM fonctionnelle et perspec- tives thérapeutiques dans la schizophrénie. Médecine humaine et pathologie. Université du Droit et de la Santé - Lille II, 2017. Français. NNT : 2017LIL2S036. tel-01956591v2 HAL Id: tel-01956591 https://tel.archives-ouvertes.fr/tel-01956591v2 Submitted on 11 Jan 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. ÉCOLE DOCTORALE BIOLOGIE ET SANTÉ UNIVERSITÉ DE LILLE Thèse d’Université DÉTECTION AUTOMATISÉE DES HALLUCINATIONS AUDITIVES EN IRM FONCTIONNELLE ET PERSPECTIVES THÉRAPEUTIQUES DANS LA SCHIZOPHRÉNIE Auteur Directeur Thomas FOVET Pr. Renaud JARDRI THÈSE SOUTENUE LE 15 DECEMBRE 2017 POUR L’OBTENTION DU GRADE DE DOCTEUR DE L’UNIVERSITÉ DE LILLE DISCIPLINE : NEUROSCIENCES JURY Pr. Arnaud CACHIA, Université Sorbonne-Paris-Cité - Rapporteur Dr. Emilie OLIE, CHU & Université de Montpellier - Rapporteur Dr. Ingrid DE CHAZERON, CHU de Clermont-Ferrand - Assesseur Pr. Pierre THOMAS, Université & CHU de Lille - Assesseur Dr. Delphine PINS, CNRS & Université de Lille - Assesseur Pr. Renaud JARDRI, Université & CHU de Lille - Directeur de Thèse “There are two kinds of truth: the truth that lights the way and the truth that warms the heart. The first of these is science, and the second is art. Neither is independent of the other or more important than the other. Without art science would be as useless as a pair of high forceps in the hands of a plumber. Without science art would become a crude mess of folklore and emotional quackery. The truth of art keeps science from becoming inhuman, and the truth of science keeps art from becoming ridiculous.” Raymond Chandler, Great Thought, February 19, 1938 1 TABLE DES MATIERES 2 LISTE DES FIGURES ET TABLEAUX 4 LISTE DES ABREVIATIONS 5 RESUME 6 MOTS-CLES 8 1 INTRODUCTION 9 1.1 HISTOIRE GENERALE DU CONCEPT 13 1.2 CONTEXTE CLINIQUE : LES HALLUCINATIONS DANS LA SCHIZOPHRENIE 14 1.3 PHYSIOPATHOLOGIE DES HALLUCINATIONS AUDITIVES DANS LA SCHIZOPHRENIE 20 1.3.1 PRINCIPAUX MODELES NEUROPSYCHOLOGIQUES 20 1.3.2 ÉTUDES D’IMAGERIE CEREBRALE 22 1.3.2.1 Imagerie structurale et hallucinations auditives 22 1.3.2.2 Imagerie fonctionnelle et hallucinations auditives 25 1.3.2.2.1 Principaux résultats des études "trait" 25 1.3.2.2.2 Principaux résultats des études "état" 26 1.3.2.3 Études de connectivité et hallucinations auditives 29 1.3.2.3.1 Connectivité fonctionnelle et connectivité effective 29 1.3.2.3.2 Connectivité anatomique (ou structurale) 32 1.3.2.4 Vers le développement de biomarqueurs spécifiques des hallucinations auditives ? 33 1.4 PRISE EN CHARGE DES HALLUCINATIONS 35 1.4.1 TRAITEMENTS MEDICAMENTEUX 35 1.4.2 TRAITEMENTS NON MEDICAMENTEUX : PSYCHOTHERAPIES 37 1.4.3 TRAITEMENTS NON MEDICAMENTEUX : LES NOUVELLES PISTES 38 1.4.3.1 Stimulation transcrânienne par courant continu 38 1.4.3.2 Stimulation magnétique transcrânienne et neuronavigation 39 1.4.3.3 Optimiser les stratégies thérapeutiques grâce à la capture hallucinatoire ? 40 1.5 OBJECTIFS DE LA THESE 41 2 DETECTION AUTOMATISEE DES HALLUCINATIONS AUDITIVES EN IRM FONCTIONNELLE 43 2.1 LA CAPTURE « OFFLINE » DE L’HALLUCINATION AUDITIVE 45 2.2 LA CAPTURE « ONLINE » DE L’HALLUCINATION AUDITIVE 69 2.2.1 GENERALITES SUR LES METHODES D’APPRENTISSAGE AUTOMATIQUE (MACHINE-LEARNING) 69 2.2.2 DEVELOPPEMENT D’UN CLASSIFICATEUR CAPABLE DE DETECTER LES PERIODES HALLUCINATOIRES : UTILISATION DU LINEAR SUPPORT VECTOR MACHINE 73 2.2.3 DEVELOPPEMENT D’UN CLASSIFICATEUR CAPABLE DE DETECTER LES PERIODES PRE-HALLUCINATOIRES ET COMPARAISON DU LINEAR SUPPORT VECTOR MACHINE AU TV-ELASTIC-NET 88 2 3 PERSPECTIVES THERAPEUTIQUES DANS LA SCHIZOPHRENIE 111 3.1 LES TECHNIQUES DE NEUROFEEDBACK 112 3.1.1 GENERALITES 112 3.1.2 INITIATIVES ACTUELLES : LA CREATION DU GROUPE NEXT 127 3.1.2.1 Recommandations de bonne pratique 127 3.1.2.2 Formation 128 3.1.2.3 Promotion de la recherche 128 3.1.2.4 Diffusion 128 3.1.3 POLEMIQUES ACTUELLES SUR L’EFFICACITE DU NEUROFEEDBACK 174 3.2 LE NEUROFEEDBACK GUIDE PAR IRMF : UTILISATION EN PSYCHIATRIE 179 3.3 LE NEUROFEEDBACK DANS LA PRISE EN CHARGE DES HALLUCINATIONS AUDITIVES 205 3.3.1 NEUROFEEDBACK GUIDE PAR EEG 205 3.3.2 NEUROFEEDBACK GUIDE PAR IRMF 206 4 DISCUSSION 231 4.1 QUELLE INTERFACE DE NEUROFEEDBACK ? 232 4.2 PROTOCOLE D’ENTRAINEMENT ET EVALUATION 235 4.3 UNE VERITABLE PSYCHOTHERAPIE GUIDEE PAR L’IMAGERIE ? 240 4.4 PERSPECTIVES 242 5 CONCLUSION 248 6 ANNEXES 250 BIBLIOGRAPHIE 254 3 LISTE DES FIGURES ET TABLEAUX Figure 1. Illustration de l’approche dimensionnelle pour explorer les hallucinations auditives. Tableau 1. Description des principaux types d’hallucinations. Figure 2. Co-occurrence des modalités hallucinatoires dans une cohorte de 171 patients souffrant de schizophrénie et d’hallucinations selon au moins une modalité. Tableau 2a. Principales échelles d’évaluation des hallucinations auditives Tableau 2b. Principales échelles d’évaluation des hallucinations (toutes modalités sensorielles confondues) Figure 3. Modifications cérébrales associées aux hallucinations auditives en imagerie structurale. Figure 4. Activations per-hallucinatoires chez un sujet. Tableau 3. Principaux résultats des méta-analyses incluant les études de capture de l’hallucination auditive. Figure 5. Les différents types de connectivité. Figure 6. Résumé du modèle quadripartite proposé par Lefebvre et collaborateurs. Figure 6. Représentation du faisceau arqué. Figure 7. Représentation du faisceau arqué. Tableau 4. Exemples de biomarqueurs en imagerie dans le domaine des hallucinations auditives. Figure 8. Evolution de la symptomatologie hallucinatoire chez 362 patients présentant un premier épisode psychotique, 1, 3, 6, 9 et 12 mois après la mise en place d’un traitement antipsychotique. Figure 9. Présentation de la méthode permettant de labelliser les volumes d’une session IRMf de repos en périodes hallucinatoires ou non-hallucinatoires. Figure 10. Principe de classification d’un linear Support Vector Machine (lSVM). Figure 11. Evolution du nombre de publications sur le neurofeedback (recherche réalisée dans la base de données Medline avec le mot clé « neurofeedback »). Figure 12. Principe du neurofeedback « décodé ». Figure 13. Proposition d’une interface multi-classificateurs pour la pris en en charge des hallucinations auditives par neurofeedback guidé par IRMf. Figure 14. Présentation du design d’un essai contrôlé randomisé visant à évaluer l’efficacité d’un protocole de neurofeedback guidé par IRMf dans le traitement des hallucinations auditives chez les patients souffrant de schizophrénie. Figure 15. Résumé du parcours du participant à l’étude. 4 LISTE DES ABRÉVIATIONS AFPBN : Association française de psychiatrie biologique et de neuropharmacologie ARMS : At Risk Mental State DTI : Diffusion Tensor Imaging EEG : électroencéphalographie lSVM : linear Support Vector Machine IRM : imagerie par résonance magnétique IRMf : imagerie par résonance magnétique fonctionnelle MCI : Mild Cognitive Impairment MEG : magnétoencéphalographie NExT : Neurofeedback Evaluation & Training rTMS : repetitive transcranial magnetic stimulation (rTMS) TEP : tomographie par émission de positons TDCS : transcranial direct current stimulation 5 RESUME L’hallucination est une expérience subjective vécue en pleine conscience consistant en une perception impossible à distinguer d’une perception réelle, mais survenant en l’absence de tout stimulus en provenance de l’environnement externe. Les symptômes hallucinatoires, qui peuvent concerner toutes les modalités sensorielles, sont retrouvés dans divers troubles neurologiques et psychiatriques mais également chez certains sujets indemnes de toute pathologie. Dans le champ de la psychiatrie, la pathologie la plus fréquemment associée aux hallucinations reste la schizophrénie et la modalité auditive est la plus représentée, puisque 60 à 80% des patients souffrant de ce trouble sont concernés. Le retentissement fonctionnel des hallucinations auditives peut être important, altérant significativement la qualité de vie des patients. Dans ce contexte, la prise en charge de ce type de symptômes s’avère un enjeu considérable pour les personnes souffrant de schizophrénie. Pourtant, les moyens thérapeutiques actuellement disponibles (traitements médicamenteux antipsychotiques notamment) ne permettent pas toujours une rémission complète de la symptomatologie hallucinatoire et l’on considère que 25 à 30% des hallucinations auditives sont « pharmaco-résistantes ». C’est à partir de ce constat que, ces dernières années, ont émergé, pour le traitement des hallucinations auditives, des techniques de neuromodulation comme la stimulation magnétique transcrânienne répétée ou la stimulation électrique transcrânienne par courant continu. Toutefois, les résultats de ces nouvelles thérapies sur les hallucinations auditives résistantes restent modérés et le développement de stratégies alternatives demeure un
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