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An Imaging-Genetic Study of the Asymmetries in the Temporal Lobe Structures : Association of These Human-Specific Markers of Development with Genetics Yann Le Guen

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An Imaging-Genetic Study of the Asymmetries in the Temporal Lobe Structures : Association of These Human-Specific Markers of Development with Genetics Yann Le Guen An imaging-genetic study of the asymmetries in the temporal lobe structures : association of these human-specific markers of development with genetics Yann Le Guen To cite this version: Yann Le Guen. An imaging-genetic study of the asymmetries in the temporal lobe structures : asso- ciation of these human-specific markers of development with genetics. Computer science. Université Paris Saclay (COmUE), 2018. English. NNT : 2018SACLS268. tel-01883649 HAL Id: tel-01883649 https://tel.archives-ouvertes.fr/tel-01883649 Submitted on 28 Sep 2018 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. Etude en imagerie-génétique des asymétries des structures du lobe temporal : association de leurs : 2018SACLS268 caractéristiques propres à l'homme NNT avec des données génétiques Thèse de doctorat de l'Université Paris-Saclay préparée à l’Université Paris Sud, Neurospin (CEA) École doctorale n°575 : electrical, optical, bio : physics and engineering (EOBE) Spécialité de doctorat : Imagerie et physique médicale Thèse présentée et soutenue à Gif-sur-Yvette, le 24 septembre 2018, par Yann Le Guen Composition du Jury : Florence d’Alché-Buc Professeur, Télécom Paristech, Paris, France Présidente du jury Peter Kochunov Professeur, Université du Maryland, Washington, USA Rapporteur Roberto Toro Directeur de recherche, Institut Pasteur, Paris, France Rapporteur Pascal Belin Professeur, INT, Marseille, France Examinateur Vincent Frouin Directeur de recherche, Neurospin, CEA, Saclay, France Directeur de thèse Ghislaine Dehaene-Lambertz Professeur, Neurospin, INSERM U992, Saclay, France Co-Directrice de thèse Titre : Etude en imagerie-génétique des asymétries des structures du lobe temporal : association de leurs caractéristiques propres à l'homme avec des données génétiques Mots clés : imagerie génétique, asymétries cérébrales, lobe temporal, IRM, traits spécifiques humains Résumé : La structure asymétrique du lobe gauche est plus souvent interrompu par un PP temporal a déjà été démontrée. Ces asymétries que son homologue à droite. Secondement, structurelles sont souvent supposées comme l’héritabilité de la profondeur des racines support à la latéralisation du langage chez sulcales dans le STS et de la présence de PP est l’homme. Une asymétrie remarquable est celle supérieure dans l’hémisphère gauche. Ceci du sillon temporal supérieur (STS) observée dès suggère des signaux génétiques asymétriques la naissance chez l’homme, mais pas chez le qui contribuent à la formation des asymétries de chimpanzé. Dans cette thèse, nous nous structures du lobe temporal. intéressons aux origines génétiques sous- Par ailleurs, nous avons montré que les jacentes à cette asymétrie. Dans ce but, nous activations fonctionnelles dans le gyrus utilisons des méthodes d’extraction angulaire ont une variance génétique partagée automatiques de structures asymétriques comme significative avec la performance cognitive. les racines sulcales ou les gyri transverses (plis Enfin, nous avons identifié une zone cis- de passage, PPs). Premièrement, nous régulatrice du gène KCNK2, comme reproduisons l’asymétrie de profondeur du STS significativement associée avec la largeur et dans deux grandes cohortes (HCP et UK l’épaisseur corticale des sillons, qui sont des Biobank) et nous démontrons que le STS caractéristiques du vieillissement du cerveau. Title: An imaging-genetic study of the asymmetries in the temporal lobe structures: association of these human-specific markers of development with genetics Keywords: imaging genetics, brain asymmetries, temporal lobe, MRI, human specific traits Abstract: The asymmetrical structure of the Second, the heritability estimates of depth and temporal lobe has already been demonstrated. convexity of sulcal roots in the STS and the These structural asymmetries are often presence of PP are higher in the left assumed to contribute to the human language hemisphere. This suggests asymmetric genetic lateralization. One noticeable asymmetry is the cues contributing to the formation of these one of the superior temporal sulcus (STS) asymmetrical structures in the temporal lobe. depth observed from birth in humans, but not in In addition, we have shown that the functional chimpanzee. In this thesis, we were interested activations in the angular gyrus have a in the genetic roots underlying this asymmetry. significant shared genetic variance with the To this aim, we used automated extraction human cognitive performance. method of asymmetrical structures such as the Finally, we have identified a cis-regulating sulcal roots or transverse gyri (so called plis de region of the KCNK2, as being significantly passage, PPs). First, we reproduced the STS associated with the width and cortical thickness rightward depth asymmetry in two large of the brain sulci, which are features of brain cohorts (HCP and UK Biobank) and we ageing. demonstrated that the left STS is more often interrupted by a PP than its counterpart. Université Paris-Saclay Espace Technologique / Immeuble Discovery Route de l’Orme aux Merisiers RD 128 / 91190 Saint-Aubin, France Introduction and context of the study ....................................................................................... 6 1. Brain cortical folding .......................................................................................................... 7 1.1. Modelling the mechanical forces ................................................................................ 7 1.2. Modelling the cellular mechanisms ............................................................................ 8 1.2.1. The corticogenesis ................................................................................................ 9 1.2.2. Cellular mechanisms leading to folding ............................................................. 10 1.2.3. The genetic program .......................................................................................... 11 1.2.4. Summary ............................................................................................................ 13 1.3. Conclusion ................................................................................................................. 13 2. Brain asymmetries ............................................................................................................ 13 2.1. Asymmetries in the human adults’ brain .................................................................. 13 2.2. Asymmetries in the human infant’s brain ................................................................. 15 2.3. Comparison with non-human primates and the human-specific STS asymmetry ... 15 2.4. Relationship between functional and structural asymmetries ................................. 17 3. Imaging Genetics .............................................................................................................. 18 3.1. Definitions ................................................................................................................. 18 3.1.1. Measured data - Essentials ................................................................................ 18 3.1.2. SNPs bi-allelic coding .......................................................................................... 19 3.1.3. The heritability ................................................................................................... 19 3.2. Cohorts investigated ................................................................................................. 20 3.2.1. The Human Connectome Project cohort ........................................................... 21 3.2.2. The UK Biobank project (January 2018 release) ................................................ 23 3.3. Imaging genetics methods ........................................................................................ 24 3.3.1. Heritability studies ............................................................................................. 24 3.3.2. Univariate association analysis .......................................................................... 27 3.4. Discussion on the imaging-genetics practices ........................................................... 28 4. Thesis rationale and plan ................................................................................................. 29 Chapter 1. Genetic Influence on the Sulcal Pits: on the Origin of the First Cortical Folds 31 1. Introduction to the chapter.............................................................................................. 31 2. Abstract ............................................................................................................................ 31 3. Introduction ...................................................................................................................... 31 4. Materials and methods .................................................................................................... 33 4.1. Pits extraction ............................................................................................................ 33 4.1.
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