Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2018 The sleep onset transition: a connectivity investigation built on EEG source localization Fernández Guerrero, Antonio Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-153590 Dissertation Published Version Originally published at: Fernández Guerrero, Antonio. The sleep onset transition: a connectivity investigation built on EEG source localization. 2018, University of Zurich, Faculty of Science. The Sleep Onset Transition: a Connectivity Investigation Built on EEG Source Localization Dissertation zur Erlangung der naturwissenschaftlichen Doktorwürde (Dr. sc. nat.) vorgelegt der Mathematisch-naturwissenschaftlichen Fakultät der Universität Zürich von Antonio Fernández Guerrero aus Spanien Promotionskommission Prof. Dr. Peter Achermann (Vorsitz und Leitung der Dissertation) Prof. Dr. Jean-Marc Fritschy Prof. Dr. Dr. med. Klaas Enno Stephan Zürich, 2018 Acknowledgements I want to credit special thanks to the following people for helping me, in one way or another, to make possible the final redaction of this thesis: Prof. Dr. Alexander Borbély (for helping with the corrections on most chapters of this thesis and offering additional insightful remarks), Dr. Benjamin Stucky and Dr. Dario Dornbierer (for helping with the German translation of the abstract), Mr. Ian Clark (for helping with the writing style and use of correct grammar) and Dr. Leila Tarokh (for her fruitful feedback on chapter 3). Special thanks to Prof. Dr. Peter Achermann, whom I consider a true mentor, for steadily supporting me in numerous ways during all these years and, most importantly, having being the most crucial figure in my formation as a neuroscientist. Table of contents i Table of Contents Summary ......................................................................................... vi Zusammenfassung .......................................................................... xi 1. Sleep, its potential functions and sleep onset ............................... 1 1.1. Sleep phases and principal neurophysiological mechanisms ..... 1 1.1.1. NREM sleep .......................................................................... 4 1.1.2. REM sleep ............................................................................. 7 1.2. Biological functions and evolutionary theory of sleep ............. 10 1.2.1. Energy conservation and allocation theory ......................... 12 1.2.2. Glymphatic system and immune boosting .......................... 15 1.2.3. Brain plasticity, memory and learning ................................ 18 1.3. Sleep onset ................................................................................. 22 1.3.1. Sleep onset transition: neurophysiological aspects ............. 22 1.3.2. Sleep onset transition: insights from latest quantitative research ............................................................................... 25 2. Brain connectivity and EEG source localization ....................... 39 2.1. Brain connectivity: introductory overview ............................... 39 2.1.1. Structural connectivity ........................................................ 42 2.1.2. Functional connectivity ....................................................... 44 2.1.3. Effective connectivity ......................................................... 46 2.2. Source localization with focus on low resolution electromagnetic tomography (LORETA) .............................................................. 50 2.3. Applications of LORETA to sleep ............................................ 56 3. Brain dynamics during the sleep onset transition: an EEG source localization study ............................................................... 72 3.1. Introduction ................................................................................ 73 3.2. Methods ...................................................................................... 75 3.3. Results ........................................................................................ 77 ii Table of contents 3.3.1. Temporal evolution of delta activity at sleep onset ............ 77 3.3.2. Temporal evolution of sigma (spindle) activity at sleep onset ............................................................................................. 84 3.3.3. Temporal evolution of alpha activity at sleep onset ............ 91 3.3.4. Temporal evolution of beta activity at sleep onset .............. 92 3.3.5. Temporal evolution of theta activity at sleep onset ............ 92 3.4. Discussion .................................................................................. 93 3.4.1. Delta activity ....................................................................... 93 3.4.2. Sigma activity ...................................................................... 95 3.4.3. Other frequency bands ......................................................... 97 3.5. Limitations ................................................................................. 98 3.6. Conclusions ................................................................................ 98 3.7. Supplementary Material ............................................................ 99 3.7.1. Supplementary Methods ...................................................... 99 3.7.2. Supplementary Results ...................................................... 100 3.7.2.1. Temporal evolution of apha activity at sleep onset ........................................................................................ 100 3.7.2.2. Temporal evolution of beta activity at sleep onset ........................................................................................ 104 3.7.2.3. Temporal evolution of theta activity at sleep onset ........................................................................................ 107 4. Assessing intracortical causal information flow of oscillatory activity at the sleep onset transition with the isolated effective coherence (iCOH) ....................................................................... 111 4.1. Introduction .............................................................................. 112 4.2. Methods .................................................................................. 114 4.2.1. Data description and preprocessing ................................... 114 4.2.2. Isolated effective coherence (iCOH) ................................. 116 4.2.3. Selection of ROIs .............................................................. 117 4.2.4. Presentation of results and statistical analyses .................. 119 Table of contents iii 4.3. Results ...................................................................................... 120 4.3.1. iCOH spectra ...................................................................... 120 4.3.1.1. Baseline condition .............................................. 120 4.3.1.2. Recovery condition ............................................. 122 4.3.1.3. Statistical contrast between baseline and recovery conditions ........................................................................ 123 4.3.2. iCOH of specific frequency bands ..................................... 124 4.3.2.1. Delta band ........................................................... 126 4.3.2.2. Sigma band ......................................................... 127 4.3.2.3. Additional frequency bands ................................ 128 4.4. Discussion ................................................................................ 130 4.4.1. Relevant spectral features of iCOH ................................... 130 4.4.1.1. Baseline ............................................................... 130 4.4.1.2. Recovery .............................................................. 131 4.4.1.3. Recovery versus baseline .................................... 132 4.4.2. Topographical properties and neurobiological interpretation ............................................................................................ 132 4.5. Supplementary Material ........................................................... 140 4.5.1. Brief explanation of iCOH formula and characteristics .... 140 4.5.2. Theoretical aspects ............................................................. 142 4.5.3. Statistics ............................................................................. 144 4.5.4. Extended discussion on additional frequency bands ......... 145 5. Summary of connectivity methods and their applications in sleep research ............................................................................... 150 5.1. Introduction .............................................................................. 151 5.2. Functional connectivity (FC) .................................................. 158 5.2.1. Information theory ............................................................. 158 5.2.2. Mutual information (MI) .................................................... 159 5.2.2.1. Cross-mutual information (CMI) ....................... 161 5.2.2.2. Auto-mutual information (AMI) ........................ 162 5.2.3. Partial information (PI) ...................................................... 164 iv Table of contents 5.2.3.1. Partial mutual information (PMI) ....................... 165 5.2.4. Applications to sleep EEG recordings............................... 172 5.3. Effective connectivity ............................................................