Mapping of Executive Functions in Children and Adolescents

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Mapping of Executive Functions in Children and Adolescents

Transcript Of Mapping of Executive Functions in Children and Adolescents

Year: 2016

Zurich Open Repository and Archive University of Zurich University Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch

Mapping of executive functions in children and adolescents born very preterm
Wehrle, Flavia

Abstract: Executive function deficits are among the most frequent sequela of very preterm birth but the underlying neuronal mechanisms are not yet fully understood. This thesis contributes to a better understanding by adopting a multimodal approach: Neurodevelopmental assessments were combined with quantitative magnetic resonance imaging (MRI) assessing brain structure and high-density electroencephalography (EEG) assessing brain function to map executive functions in children and adolescents born very preterm. The results show that even those individuals born very preterm with normal intellectual abilities may experience executive function deficits if the demands placed on their abilities are high. Smaller volumes of subcortical brain regions, particularly of the thalamus, were found to be related to poorer working memory abilities, one of the key executive processes. Applying high-density EEG during sleep revealed that individuals born very preterm express higher sleep slow wave activity over brain regions associated with executive processes compared to term-born peers. As sleep slow waves are thought to reflect the synchronized oscillatory activity of the thalamocortical system, these findings contribute further to the overall finding of this thesis: The thalamocortical system appears to be crucially involved in executive processes and the multimodal assessment of its structural and functional integrity provides novel insight into the long-term consequences of very preterm birth.

Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-131858 Dissertation Published Version
Originally published at: Wehrle, Flavia. Mapping of executive functions in children and adolescents born very preterm. 2016, University of Zurich, Faculty of Arts.

Mapping of Executive Functions in Children and Adolescents Born Very Preterm
Thesis (cumulative thesis) presented to the Faculty of Arts and Social Sciences
of the University of Zurich for the degree of Doctor of Philosophy
by Flavia Maria Wehrle
Accepted in the fall semester 2016 on the recommendation of the doctoral committee:
Prof. Dr. Lutz Jäncke (main supervisor) Prof. Dr. Reto Huber Prof. Dr. Beatrix Latal
Zurich, 2016

Table of Contents

1 Summary ................................................................................................................................ v

2 Zusammenfassung .............................................................................................................. vii

3 Introduction ........................................................................................................................... 9

3.1 Very preterm birth – A risk for neurodevelopmental deficits ............................................................ 9 3.1.1 Definition, prevalence and consequences of very preterm birth .......................................................... 9 3.1.2 Executive functions and executive function deficits following very preterm birth ............................ 10 3.1.3 Prenatal brain development and alterations due to very preterm birth ............................................... 12

3.2 Multimodal assessment of structural and functional neuroanatomy ............................................... 14

3.2.1 3.2.2 3.2.3

Assessing executive function abilities................................................................................................ 14 Assessing the structural neuroanatomy of executive processes ......................................................... 15 Assessing functional neuroanatomy during sleep .............................................................................. 16

3.3 Aims of this thesis ................................................................................................................................. 20

4 Research articles ................................................................................................................. 23
4.1 Very Preterm Adolescents Show Impaired Performance With Increasing Demands In Executive Function Tasks ...................................................................................................................................... 25
4.2 Subcortical Cerebral Volume Is Associated With Working Memory Performance in Adolescents Born Very Preterm ............................................................................................................................... 41
4.3 Sleep Spindles Predict Schizotypal Personality Traits and Thalamic Glutamine/ Glutamate in Healthy Subjects ................................................................................................................................... 57
4.4 The Multidimensional Aspects of Sleep Spindles and Their Relationship to Word-Pair Memory Consolidation......................................................................................................................................... 77
4.5 Sleep EEG maps the functional neuroanatomy of executive processes in adolescents born very preterm ................................................................................................................................................ 101

5 Discussion ........................................................................................................................... 121

5.1 Executive function abilities in today’s cohorts of very preterm survivors..................................... 121 5.2 Subcortical structures and executive function abilities ................................................................... 124

5.2.1 Interventions to protect structural correlates of executive function abilities?.................................. 126

5.3 Functional integrity of brain networks in typical and atypical brain development...................... 127

5.3.1 5.3.2

Sleep spindles as a marker of thalamocortical integrity and efficiency ........................................... 127 Sleep SWA to map the functional neuroanatomy of executive processes........................................ 129

5.4 How are structure and function related in typical and atypical brain development? .................. 132 5.5 How can the current findings improve long-term outcome after very preterm birth? ................ 133 5.6 Limitations........................................................................................................................................... 134 5.7 Concluding remarks ........................................................................................................................... 135

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6 References .......................................................................................................................... 137 7 Curriculum Vitae.............................................................................................................. 153 8 Publication list ................................................................................................................... 157 9 Acknowledgements ........................................................................................................... 161
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1

S um ma ry

1

Summary

Executive function deficits are among the most frequent sequela of very preterm birth but the underlying neuronal mechanisms are not yet fully understood. This thesis contributes to a better understanding by adopting a multimodal approach: Neurodevelopmental assessments were combined with quantitative magnetic resonance imaging (MRI) assessing brain structure and high-density electroencephalography (EEG) assessing brain function to map executive functions in children and adolescents born very preterm. The results show that even those individuals born very preterm with normal intellectual abilities may experience executive function deficits if the demands placed on their abilities are high. Smaller volumes of subcortical brain regions, particularly of the thalamus, were found to be related to poorer working memory abilities, one of the key executive processes. Applying high-density EEG during sleep revealed that individuals born very preterm express higher sleep slow wave activity over brain regions associated with executive processes compared to term-born peers. As sleep slow waves are thought to reflect the synchronized oscillatory activity of the thalamocortical system, these findings contribute further to the overall finding of this thesis: The thalamocortical system appears to be crucially involved in executive processes and the multimodal assessment of its structural and functional integrity provides novel insight into the long-term consequences of very preterm birth.

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Zu samm en fa ssu ng

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Zusammenfassung

Defizite in exekutiven Funktionen gehören zu den häufigsten Folgen von Frühgeburtlichkeit, die zugrundeliegenden neuronalen Mechanismen sind bislang aber noch nicht ausreichend bekannt. Um einen Beitrag zum besseren Verständnis zu leisten bedient sich die vorgelegte Dissertation eines multimodalen Ansatzes: Entwicklungsdiagnostische Verfahren werden mit quantitativer Magnetresonanztomographie zur Erfassung der Hirnstruktur sowie hochauflösenden elektroencephalografischen (EEG)-Aufzeichnungen im Schlaf zur Erfassung der Hirnfunktion kombiniert. Es wurde gezeigt, dass frühgeborene Kinder trotz normaler kognitiver Fähigkeiten Defizite in exekutiven Funktionen aufweisen, wenn hohe Anforderungen an die Fähigkeiten gestellt werden. Ein geringes Volu men subkortikaler Hirnstrukturen, insbesondere des Thalamus, war assoziiert mit schlechten Arbeitsgedächtnisfähigkeiten, einer bedeutenden exekutiven Fähigkeit. Frühgeborene Kinder zeigten zudem in Hirnregionen, welche mit exekutiven Prozessen zusammenhängen, mehr Tiefschlafaktivität als termingeborene Kinder. Da Tiefschlafwellen die synchronisierte oszillierende Aktivität des thalamokortikalen Systems reflektieren, unterstützt dieses Ergebnis die übergeordnete Erkenntnis dieser Dissertation: Das thalamokortikale System spielt eine wichtige Rolle für exekutive Fähigkeiten und die multimodale Untersuchung seiner strukturellen sowie funktionellen Integrität kann neue Einsichten in die langfristigen Folgen von Frühgeburtlichkeit liefern.

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In tro du ction

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Introduction

Very preterm birth is a significant risk factor for impaired brain development and later neurodevelopmental deficits. Particularly, executive function abilities are frequently impaired in today’s cohorts of very preterm survivors, however, the specific underlying neuronal mechanisms have yet to be understood. The current thesis has adopted a multimodal approach employing cognitive and behavioral assessments, structural magnetic resonance imaging (MRI) and electroencephalographic (EEG) measures of brain functioning to investigate potential alterations in the structural and functional neuroanatomy of executive processes in children and adolescents born very preterm. This may provide novel insight into the long-term consequences of early disruptions to normal brain development and foster the identification of specific targets for neuroprotective agents and cognitive interventions to improve neurodevelopmental outcome following very preterm birth.
In the first part of the introduction, an overview on very preterm birth and the respective consequences for neurodevelopment will be provided. Next, methodological considerations related to the multimodal approach employed in this thesis will be introduced. Finally, the aims of the current thesis will be presented.

3.1 Very preterm birth – A risk for neurodevelopmental deficits 3.1.1 Definition, prevalence and consequences of very preterm birth
Very preterm birth describes birth before 32 weeks of gestation and occurs in 1% of all life-births (Tucker and McGuire, 2004). In Switzerland, this equals approximately 800 babies every year (BFS, 2015b). The risk factors for preterm birth are manifold and include low or high maternal age, multiple gestation, hypertensive disorders of pregnancy, intrauterine infections, intrauterine growth restriction, cervical shortening or psychological and social stress (see Tucker and McGuire, 2004 for an overview). The increase of maternal age (e.g. from 27.8 years in 1970 to 31.7 years in 2014 in Switzerland (BFS, 2015a)) and the increased number of multiple births, presumably due to the increase in assisted reproduction, are the main contributors of the increase in preterm births reported for most industrialized countries over the
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Preterm BirthPretermAdolescentsExecutive ProcessesThesis