Improving EEG: From Simulations to Applications Inaugural-Dissertation zur Erlangung der Doktorwürde der Fakultät für Biologie der Albert-Ludwigs-Universität Freiburg im Breisgau vorgelegt von Lukas Dominique Josef Fiederer geboren in Meyrin, Schweiz Freiburg im Breisgau Juli 2018 Angefertigt an der Uniklinik Freiburg The research presented in this thesis was carried out at the Institute for Biology I of the Albert-Ludwig-University Freiburg, in collaboration with the University Hospital of the University of Freiburg, from September 2012 to August 2017. Dekanin der Fakultät für Biologie: Prof. Dr. Bettina Warscheid Promotionsvorsitzender: Prof. Dr. Andreas Hiltbrunner Betreuer der Arbeit: PD Dr.med. Tonio Ball Referent: PD Dr. med. Tonio Ball Koreferent: Drittprüfer: Datum der mündlichen Prüfung: 1 Table of Contents TABLE OF CONTENTS ACKNOWLEDGEMENTS ..................................................................................................................................................... 3 DECLARATION ...................................................................................................................................................................... 4 ABSTRACT .............................................................................................................................................................................. 6 I. INTRODUCTION ......................................................................................................................................................... 9 1) Electroencephalography ................................................................................................................................................. 9 A. ELECTROPHYSIOLOGY ................................................................................................................................................................. 9 2) Electrocorticography & stereotactic electroencephalography ..................................................................... 10 3) Local field potentials ...................................................................................................................................................... 11 4) Multi-unit & single-unit activity ................................................................................................................................ 12 B. MAGNETIC RESONANCE IMAGING ........................................................................................................................................... 12 C. VOLUME CONDUCTOR HEAD MODELING ............................................................................................................................... 14 D. SOMATOSENSORY EVOKED POTENTIALS ............................................................................................................................... 16 II. E. SUMMARYOBJECT OF OF THIS THE THESIS RESUL ............................................................................................................................................................TS .............................................................................................................................. 18 16 A. SPATIAL AND FREQUENCY-DOMAIN CHARACTERISTICS OF INTRACRANIALLY-MEASURED EMG ................................ 18 B. ENDOGENOUS BRAIN STIMULATION THROUGH EMG ......................................................................................................... 18 C. VOLUME CONDUCTION MODELING OF BLOOD VESSELS ..................................................................................................... 18 III.D. DISCUSSIONMODELING µ..............................................................................................................................................................ECOG NEURONAL SOURCES (BASED ON 2 PAPERS) ..................................................................................... 19 18 A. MODEL-GUIDED IMPROVEMENTS OF INTRACRANIAL ELECTROPHYSIOLOGICAL MEASUREMENTS ............................. 19 B. CHEWING-RELATED ENDOGENOUS BRAIN STIMULATION: FURTHER STEPS TO PROVE HYPOTHESIS ....................... 21 C. CHEWING-RELATED ENDOGENOUS BRAIN STIMULATION– : BENEFICIAL OR DETRIMENTAL? THOUGHTS ON APPLICATIONS TO EVOLUTION AND FOOD INTAKE ......................................................................................................................... 22 D. BLOOD VESSELS AS WINDOWS TO THE BRAIN A RECORDING AND STIMULATION PERSPECTIVE............................. 23 IV.E. REFERENCESDEPTH LOCALIZATION ............................................................................................................................................................ OF NEURONAL ACTIVITY ................................................................................................................. 27 25 V. SPATIAL AND FREQUENCY-DOMAIN CHARACTERISTICS OF INTRACRANIALLY- MEASURED EMG ................................................................................................................................................................ 35 VI. ELECTRICAL STIMULATION OF THE HUMAN CEREBRAL CORTEX BY EXTRACRANIAL MUSCLE ACTIVITY: EFFECT QUANTIFICATION WITH INTRACRANIAL EEG AND FEM SIMULATIONS ................ 51 VII. THE ROLE OF BLOOD VESSELS IN HIGH-RESOLUTION VOLUME CONDUCTOR HEAD MODELING OF EEG ........................................................................................................................................................... 65 VIII. MAPPING THE FINE STRUCTURE OF CORTICAL ACTIVITY WITH DIFFERENT MICRO-ECOG ELECTRODE ARRAY GEOMETRIES ............................................................................................................................. 83 IX. CORTICAL-DEPTH AND FREQUENCY-BAND DEPENDENCY OF THE SPATIAL EXTENT OF THE GENERATORS UNDERLYING µECOG RECORDINGS ............................................................................................ 107 2 Acknowledgements ACKNOWLEDGEMENTS I would like to thank my supervisor, Tonio Ball, for his continued support and valuable guidance. Without him and the possibilities he created this work would not have been possible and I would probably not be the same ;-) Thank you Tonio! I would like to thank my colleagues for their support, for all the more or less fruitful discussions and for the great times spent together :-D You know who you are! I would like to thank my parents who have made my studies possible and who infused me with the moral and perseverance I needed to accomplish my PhD. Without them I would have sought much quicker ‘satisfaction’. Merci maman, danke Papa! <3 I would like to thank the love of my life, who incidentally became my wife during this work, and my children, born during this work, for lighting up my life. Without them life would be much more … dull … (and quiet). Merci mes chéries! <3 <3 <3 Lastly, I would like to once again thank my wife, this time for all her loving support and for leveraging the tremendous of work all her ‘children’ require of her. Danke mein Schatz, ich liebe dich! 3 Declaration DECLARATION The detailed results of selected work performed during the time of the thesis can be found in the appended publications and manuscripts. The contributions of the individual authors are declared below. THE ROLE OF BLOOD VESSELS IN HIGH-RESOLUTION VOLUME CONDUCTOR HEAD MODELING OF EEG Fiederer L.D.J., Vorwerk J., Lucka F., Dannhauer M., Yang S., Dümpelmann M., Schulze- Bonhage A., Aertsen A., Speck O., Wolters C.H., Ball T. T. Ball and L.D.J. Fiederer devised the study. L.D.J. Fiederer programed and performed the segmentations, created the models, devised, ran and evaluated the simulations. J. Vorwerk, F. Lucka, M. Dannhauer, M. Dümpelmann and C.H. Wolters introduced L.D.J. Fiederer to the simulation and visualization software, provided support and counseling. S. Yang acquired the 7T MRI data and performed initial skull stripping and brain segmentation using Freesurfer, under the supervision of O. Speck. L.D.J. Fiederer and T. Ball wrote the paper with the help of J. Vorwerk, F. Lucka, M. Dannhauer, S. Yang, M. Dümpelmann, A. Schulze-Bonhage, A. Aertsen, O. Speck and C.H. Wolters. L.D.J. Fiederer created the visualizations, figures and designed the cover image. SPATIAL AND FREQUENCY-DOMAIN CHARACTERISTICS OF INTRACRANIALLY-MEASURED EMG J. Lahr, L.D.J. Fiederer, O. Iljina, A. Aertsen, A. Schulze-Bonhage, T. Ball T. Ball and J. Lahr devised the study. J. Lahr evaluated the chewing data and performed the data analysis. O. Iljina evaluated the linguistic data. J. Lahr, L.D.J. Fiederer and T. Ball wrote the paper with the help of O. Iljina, A. Aertsen and A. Schulze-Bonhage. J. Lahr created the visualizations. J. Lahr and L.D.J. Fiederer created the figures. ELECTRICAL STIMULATION OF THE HUMAN CEREBRAL CORTEX BY EXTRACRANIAL MUSCLE ACTIVITY: EFFECT QUANTIFICATION WITH INTRACRANIAL EEG AND FEM SIMULATIONS Lukas Dominique Josef Fiederer, Jacob Lahr, Johannes Vorwerk, Felix Lucka, Ad Aertsen, Carsten Hermann Wolters, Andreas Schulze-Bonhage, Tonio Ball T. Ball, L.D.J. Fiederer and J. Lahr devised the study. L.D.J. Fiederer programed and performed the segmentations, created the models, devised, ran and evaluated the simulations, measured and analyzed the non-invasive EEG data. J. Lahr analyzed the invasive EEG data. J. Vorwerk, F. Lucka, and C.H. Wolters provided support and counseling. A. Schulze-Bonhage provided access to the patients data. L.D.J. Fiederer, T. Ball and J. Lahr wrote the paper with