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Building the path to resilience in preterm infants: a neuroimaging investigation of the impact of multisensory and neurocognitive interventions

English title Building the path to resilience in preterm infants: a neuroimaging investigation of the impact of multisensory and neurocognitive interventions
Applicant Hüppi Petra
Number 163084
Funding scheme Project funding (special)
Research institution Service de Développement et Croissance Département de Pédiatrie Hôpital des Enfants - HUG
Institution of higher education University of Geneva - GE
Main discipline Paediatrics
Start/End 01.02.2016 - 31.01.2019
Approved amount 862'555.00
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All Disciplines (2)

Discipline
Paediatrics
Psychology

Keywords (6)

Emotion; Imaging; Brain; Executive function; Prematurity; Resilience

Lay Summary (French)

Lead
Les objectifs de cette étude sont d’investiguer les structures et les fonctions du cortex préfrontal (en particulier le COF) et d’évaluer l’efficacité de 3 interventions adaptées à l’âge de l’enfant à améliorer les fonctions exécutives et socio-affectives
Lay summary
Chaque année, 15 millions d’enfants naissent prématurément. A l’âge scolaire, entre 30 et 50% des enfants grands prématurés (nés avant 32 semaines de gestation) présentent des difficultés d’apprentissage et dans l’acquisition des compétences sociales. La plupart des comportements adaptatifs de notre quotidien reposent sur des interactions complexes entre les processus affectifs et motivationnels qui sont régis, entre autres, par le cortex orbitofrontal (COF), et des mécanismes de contrôle cognitif qui dépendent principalement du cortex préfrontal. Les objectifs de cette étude sont d’investiguer les structures et les fonctions du cortex préfrontal (en particulier le COF) et d’évaluer l’efficacité de 3 interventions adaptées à l’âge de l’enfant à améliorer les fonctions exécutives et socio-affectives. Une première intervention étudiera les effets d’une exposition quotidienne à une musique adaptée sur les nouveau-nés prématurés pendant tout leur séjour en néonatalogie. Un second programme d’intervention informatisé « Vis-à-Vis », visera à améliorer la reconnaissance des émotions, l’exploration du visage et la mémoire de travail d’enfants prématurés entre 6 et 9 ans. La troisième intervention proposera à des enfants prématurés entre 10 et 13 ans des séances de Pleine Conscience ou « Mindfulness », une pratique de méditation, dans le but d’améliorer leurs capacités socio-émotionnelles, attentionnelles et cognitives. Ainsi, cette recherche d’avancer dans la compréhension de la vulnérabilité cognitive et émotionnelle liée à l’immaturité cérébrale du prématuré. Plus important encore, nous allons aborder la question du renforcement de la capacité à faire face aux demandes émotionnelles et cognitives de la vie chez les enfants prématurés, en espérant ainsi empêcher l’apparition de difficultés et réduire leurs effets à l’aide d’interventions adaptées.
Direct link to Lay Summary Last update: 03.04.2019

Responsible applicant and co-applicants

Employees

Publications

Publication
Music in premature infants enhances high-level cognitive brain networks
Lordier Lara, Meskaldji Djalel-Eddine, Grouiller Frédéric, Pittet Marie P., Vollenweider Andreas, Vasung Lana, Borradori-Tolsa Cristina, Lazeyras François, Grandjean Didier, Van De Ville Dimitri, Hüppi Petra S. (2019), Music in premature infants enhances high-level cognitive brain networks, in Proceedings of the National Academy of Sciences, 201817536-201817536.
Neuroprocessing Mechanisms of Music during Fetal and Neonatal Development: A Role in Neuroplasticity and Neurodevelopment
Chorna O., Filippa M., De Almeida J. Sa, Lordier L., Monaci M. G., Hüppi P., Grandjean D., Guzzetta A. (2019), Neuroprocessing Mechanisms of Music during Fetal and Neonatal Development: A Role in Neuroplasticity and Neurodevelopment, in Neural Plasticity, 2019, 1-9.
Music processing in preterm and full-term newborns: A psychophysiological interaction (PPI) approach in neonatal fMRI
Lordier Lara, Loukas Serafeim, Grouiller Frédéric, Vollenweider Andreas, Vasung Lana, Meskaldij Djalel-Eddine, Lejeune Fleur, Pittet Marie Pascale, Borradori-Tolsa Cristina, Lazeyras François, Grandjean Didier, Van De Ville Dimitri, Hüppi Petra S. (2019), Music processing in preterm and full-term newborns: A psychophysiological interaction (PPI) approach in neonatal fMRI, in NeuroImage, 185, 857-864.
fMRI-based Neuronal Response to New Odorants in the Newborn Brain.
Adam-Darque Alexandra, Grouiller Frédéric, Vasung Lana, Ha-Vinh Leuchter Russia, Pollien Philippe, Lazeyras François, Hüppi Petra S (2017), fMRI-based Neuronal Response to New Odorants in the Newborn Brain., in Cerebral cortex (New York, N.Y. : 1991), 1-7.
Children's sense of reality: The development of orbitofrontal reality filtering.
Liverani Maria Chiara, Manuel Aurélie L, Nahum Louis, Guardabassi Veronica, Tomasetto Carlo, Schnider Armin (2017), Children's sense of reality: The development of orbitofrontal reality filtering., in Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence, 23(4), 408-421.
Inhibition difficulties in preterm children: Developmental delay or persistent deficit?
Réveillon Morgane, Hüppi Petra S, Barisnikov Koviljka (2017), Inhibition difficulties in preterm children: Developmental delay or persistent deficit?, in Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence, 1-29.
Orbitofrontal reality filtering specified: relation to temporal order memory, role of emotion, and development
Liverani Maria Chiara (2016), Orbitofrontal reality filtering specified: relation to temporal order memory, role of emotion, and development, University of Geneva, Doctoral dissertation.

Collaboration

Group / person Country
Types of collaboration
Mirjam Bickle Graz MD -MD Child Development Unit, Division of Neonatology, CHUV Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Cristina Borradori Tolsa, Child Development Unit University Childrens Hospital GE Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Alan Evans, Mc Gill Center of Integrative Neuroscience, Montreal Canada (North America)
- in-depth/constructive exchanges on approaches, methods or results
Jessica Dubois, Neurospin, CEA, Saclay, Paris, France France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Kovijlka Barisnikov, Unité de Psychologie Clinique et de Neuropsychologie de l'Enfant, Université de Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Cyril Poupon, Neurospin Saclay, France, CONNECT Consortium EU Framework 7 project France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Edouard Gentaz, Prof. of Psychology, Laboratoire du développement sensori-moteur, affectif et social Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
David Sander, PhD Professor in Psychology Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Jean Philippe Thiran CIBM Image analysis core EPFL Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Armin Schnider, Prof. of Neurology and Neurorehabilitation University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Sylviane Hanquinet, MD Associated Professor in Radiology University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Reto Meuli, Professor in Radiology CIBM Lausanne Switzerland (Europe)
- Research Infrastructure
Arnaud Merglen, MD Chef de clinique scientifique Dept of Pediatrics, Univ. GE Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Anita Truttman MD PD is one of the staff neonatologists Switzerland (Europe)
- Publication
Francois Lazeyras, Prof. in Physics CIBM Université de Geneève Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Organization for Human Brain Mapping Poster Get Real: the orbitofrontal cortex mediates pre-teenagers’ sense of reality 09.04.2019 Rome, Italy Hüppi Petra; Goncalves De Alcantara Freitas Lorena; Siffredi Vanessa; Liverani Maria Chiara; De Albuquerque Jiske;
8th symposium EADCare Individual talk Music enhances Brain development 31.10.2018 Paris, France Hüppi Petra;
ISMRM 2018 Individual talk Mansfield Lecture How Early Life Events Shape Our Brain: An MRI Perspective 17.06.2018 Paris, France Hüppi Petra;
ISMRM 2018 Talk given at a conference Early postnatal music intervention after preterm birth reorganizes brain salience network interactions 16.06.2018 Paris, France Hüppi Petra;
Journée d'inauguration Unité de développement, Hôpitaux universitaires de Genève Poster Programmes d’enrichissement pour enfants prématurés 03.03.2018 Genève, Switzerland De Albuquerque Jiske; Gonçalves de Alcântara E Freitas Lorena; Siffredi Vanessa; Liverani Maria Chiara; Hüppi Petra;
Alpine Brain Imaging Meeting Poster Psychophysiological interaction of co-activation patterns: tracking fMRI dynamics during task 07.01.2018 Champéry, Switzerland Hüppi Petra; Gonçalves de Alcântara E Freitas Lorena;
jENS: 2nd Congress of joint European Neonatal Societies Talk given at a conference Music effects in preterm infants’ brain: a structural neuroimaging investigation 30.10.2017 Venice, Italy Alves Sá de Almeida Joana Rita; Hüppi Petra;
jENS: 2nd Congress of joint European Neonatal Societies Talk given at a conference Can differences in early functional connectivity in healthy newborns exposed to olfactory stimulation help us understand crying behaviour at 6 weeks of life 30.10.2017 Venice, Italy Gonçalves de Alcântara E Freitas Lorena; Hüppi Petra;
Workshop “From activity to interactivity: harnessing early adaptive neuroplasticity for intervention in atypical development” Talk given at a conference Cerebellar volume at term equivalent age is associated with behavioral and cognitive outcome at 5 years of age of extremely preterm children 17.10.2017 Erice, Italy Liverani Maria Chiara; Hüppi Petra;
International workshop of the Neuroscience School « Sir John Eccles » Talk given at a conference Cerebellar volume at term equivalent age is associated with behavioral and cognitive outcome at 5 years of age of extremely preterm children 17.10.2017 Erice, Italy Liverani Maria Chiara; Hüppi Petra;
Lemanic Neuroscience Annual Meeting Poster Building the path to resilience in preterm infants: A neuroimaging investigation of Music structural effects in preterm infants’ brain 01.09.2017 Les Diablerets, Switzerland Alves Sá de Almeida Joana Rita; Hüppi Petra;
Organization for Human Brain Mapping Poster Psychophysiological interaction of co-activation patterns (PPI-CAPs): tracking task-dependent brain activity 25.06.2017 Vancouver, Canada Gonçalves de Alcântara E Freitas Lorena; Hüppi Petra;
BBL/CIBM scientific day Talk given at a conference Music training enhances functional connectivity in preterm newborns 21.06.2017 Geneva, Switzerland Hüppi Petra;
BBL/CIBM scientific day Talk given at a conference Effect of prematurity on functional connectivity using resting-state fMRI in newborns 21.06.2017 Geneva, Switzerland Hüppi Petra;
BBL/CIBM scientific day Poster Building the path to resilience in preterm infants: A neuroimaging investigation of Music structural effects in preterm infants’ brain 21.06.2017 Geneva, Switzerland Hüppi Petra; Alves Sá de Almeida Joana Rita;
PhD retreat Medical School of University of Geneva Poster Building the path to resilience in preterm infants: A neuroimaging investigation of Music structural effects in preterm infants’ brain 27.04.2017 Champéry, Switzerland Alves Sá de Almeida Joana Rita; Hüppi Petra;
ISMRM 2017 Talk given at a conference Music training enhances functional connectivity in preterm newborns 25.04.2017 Hawaï, United States of America Hüppi Petra;
Alpine Brain Imaging Meeting Poster PPI analysis reveals altered connectivity in preterm infants listening to their mother’s voice 08.01.2017 Champéry, Switzerland Gonçalves de Alcântara E Freitas Lorena; Hüppi Petra;
EPFL Bioengineering Institute Scientific Day Poster PPI analysis reveals altered connectivity in preterm infants listening to their mother’s voice 28.09.2016 Geneva, Switzerland Gonçalves de Alcântara E Freitas Lorena; Hüppi Petra;
EPFL Bioengineering Institute Scientific Day Poster Altered connectivity in preterm infants listening to their mother’s voice revealed by PPI analysis 28.09.2016 Geneva, Switzerland Gonçalves de Alcântara E Freitas Lorena; Hüppi Petra;


Self-organised

Title Date Place

Knowledge transfer events



Self-organised

Title Date Place

Communication with the public

Communication Title Media Place Year
New media (web, blogs, podcasts, news feeds etc.) Outlook - Why we play music to premature babies International 2019
Media relations: print media, online media D’après cette étude, la musique aiderait au développement du cerveau des grands prématurés Au féminin Suisse Rhaeto-Romanic Switzerland 2019
New media (web, blogs, podcasts, news feeds etc.) La musique aide le cerveau des grands prématurés à se construire KEYSTONE ATS - Agence Télégraphique Suisse German-speaking Switzerland 2019
Media relations: radio, television La musique aide le cerveau des prématurés à se construire RTS Rhaeto-Romanic Switzerland 2019
Media relations: radio, television La musique améliore le développement du cerveau des prématurés RTS Rhaeto-Romanic Switzerland 2019
Media relations: print media, online media La musique renforce le cerveau des prématurés Tribune de genève Rhaeto-Romanic Switzerland 2019
Media relations: print media, online media La musique stimulerait le développement des bébés prématurés Le Figaro.fr - Santé International 2019
Media relations: print media, online media Le cerveau des bébés prématurés se développe en musique Le temps Rhaeto-Romanic Switzerland 2019
New media (web, blogs, podcasts, news feeds etc.) Music helps to build the brains of very premature babies Science Daily International 2019
Media relations: print media, online media Musik fördert die Hirnentwicklung von Frühgeborenen Neue Bürcher Beitung German-speaking Switzerland 2019
Media relations: print media, online media Musik hilfen den Frühchen Tagblatt - Der Stadt Zürich German-speaking Switzerland 2019
Media relations: print media, online media Musique écrite pour aider les grands prématurés 20 minutes Rhaeto-Romanic Switzerland 2019
Media relations: print media, online media Santé: la musique aide le cerveau des grands prématurés à se construire Le Nouvelliste Rhaeto-Romanic Switzerland 2019
Media relations: print media, online media Snake charmers may make your premature babies smarter, says study India Today International 2019
Media relations: print media, online media Symphonie pour prématurés Le temps Rhaeto-Romanic Switzerland 2019
Media relations: print media, online media The food of love: neurology The economist International 2019
Media relations: print media, online media Pourquoi les chances de survie des grands prématurés se sont-elles améliorées? Le Temps Rhaeto-Romanic Switzerland 2018
Media relations: print media, online media 12 innovations that will revolutionize the future of medicine National Geographic International 2018
Media relations: print media, online media Flûte et harpe pour doper le développement des bébés Tribune de Genève Rhaeto-Romanic Switzerland 2018
New media (web, blogs, podcasts, news feeds etc.) Child Development Laboratory International 2016

Associated projects

Number Title Start Funding scheme
182832 Building the path to resilience after preterm birth: cortical development and network based interventions in longitudinal cohorts 01.02.2019 Project funding (Div. I-III)
135817 Development of Emotion and Cognition in Preterm Born Cohorts: Neurostructural and Neurofunctional Correlates from Birth to Early Adolescence 01.10.2011 Project funding (special)
124101 From cortex to classroom: enhancing brain development for premature infants 01.10.2009 SPUM
113632 Development of Executive Functions in children born prematurely in relation to neurostructural brain development 01.04.2007 Project funding (Div. I-III)
113632 Development of Executive Functions in children born prematurely in relation to neurostructural brain development 01.04.2007 Project funding (Div. I-III)
102127 Hypoxia-Ischemia in the developing brain. Correlations between electrophysiological activity, biomarkers of brain injury, advanced Magnetic Resonance Imaging and neurodevelopmental outcome 01.01.2004 Project funding (Div. I-III)

Abstract

Yearly 15 million babies worldwide are born too soon. 10% of these preterm births occur very early before 32 weeks of gestation and these newborns are at high risk for neurodevelopmental disorders later in life. Neurocognitive disorders now touch 27% of the European population, and 5% or 3.3 million children suffer from social and learning difficulties, including attention-deficit hyperactivity disorders and autism, whose rates are increasing and prematurity contributes to this rise. Cognition, and socio-emotional competence are based on intact brain structure and functions that are formed early in development, both pre- and post-natally, and are heavily influenced by environment. Ramon y Cajal in his studies on the making of the brain clearly stated: "The total arborisation of a neuron represents the graphic history of conflicts suffered during its developmental life". Understanding how environment affects early brain development and defining timing and mode of early interventions to enhance brain development in high risk populations, such as preterm infants, is currently acknowledged as a fundamental endeavor for the scientific community (see guidelines of the National Scientific Council for the Developing Child). Interventions to improve and maintain cognitive and socio-emotional skills are to become an essential tool of medical care for high-risk infants.Advanced neuroimaging, especially MRI have allowed the detection of discrete brain abnormalities early in development (from the newborn period to childhood) with a clear negative impact on global and cognitive development of preterm infants. We have in recent project further developed these imaging tools to better specify the regional vulnerability of the preterm brain and its specific alterations in brain networks linked to socio-cognitive development. The results unambiguously indicated that the prefrontal and limbic cortico-basal ganglia-thalamic structural loop was weakened in preterm born children and that these alterations correlated with specific deficits in executive functions in these children, despite their normal IQ’s. Alongside with deficits in emotional regulation evidenced as early as 12 months of age and reduced volumes of brain structures involved in the corticolimbic system, these results provide compelling support for the hypothesis that preterm birth leads to a damage of prefrontal, including orbitofrontal and limbic brain networks later sub serving executive function and affective cognition. Even though the orbitofrontal cortex (OFC), in its sulcation pattern, its thickness and its connectivity, has been shown to be especially altered as a consequence of preterm birth, studies assessing the function of the OFC in the context of preterm birth are so far missing. OFC in adults signals when an activated memory does not pertain to ongoing reality, It thus prevents behavior from being based on fantasies and is therefore essential for human behavior. Our preliminary results presented here show a clear relationship between performance in the reality filtering task in childhood and gestational age at birth, supporting our hypothesis that prematurity affects prefrontal and in particular OFC functions. Most daily adaptive behavior relies on even more complex interactions between affective and motivational processes, relying on the OFC and several other structures, and top down cognitive control mechanisms, primarily involving the prefrontal cortex (PFC). For instance, preventing attention being captured by emotional distractors in order to perform another task (such as in the emotional Flanker task), demands a successful cross-talk between orbitofrontal and prefrontal processes.As children born preterm have documented widespread difficulties in socio-emotional and executive functions, the tasks described above are ideally suited to study the function of the OFC and PFC, in the developing preterm brain. Our gaol in this proposal is fold: to perform an in-depth investigation of the structure and function of the orbitofrontal and prefrontal brain networks with advanced structural and functional imaging techniques and behavioural tasks specifically targeting these networks;to study three carefully selected age-appropriate perinatal and childhood behavioral interventions that are considered to make use of the brain networks we have described as affected by prematurity and improve socio-emotional and executive functions.First, in connection with a novel European initiative specifying the guidelines for developmental care (http://eadcare.org/), we outline a perinatal intervention to explore the effects of a music induced neuro-enhancement in preterm infants during their neonatal intensive care unit (NICU) stay. The second intervention will be a computerized emotion and working memory training called Vis-à-Vis, which will be performed in children born preterm at age 6 to 9 years. The third intervention is a mindfulness based training (intentional self-regulation of attention) to be performed in 10-13 year old preterm children, both from our prior studied preterm cohorts.Overall, our planned research will fill an important gap in our theoretical understanding of the brain vulnerability linked to prematurity. Even more importantly, we will address the compelling issue of how to build cognitive and emotional resilience in preterm children, by preventing the onset of difficulties and reducing them with appropriate interventions.
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