Connectivity and Morphology of the Primate Brain Inaugural-Dissertation zur Erlangung des Doktorgrades der Mathematisch-Naturwissenschaftlichen Fakultät der Heinrich-Heine-Universität Düsseldorf vorgelegt von Andrew Reid aus Gander, Canada Mai, 2010 Aus dem Institut für Experimentelle Psychologie der Heinrich-Heine Universität Düsseldorf Gedruckt mit der Genehmigung der Mathematisch-Naturwissenschaftlichen Fakultät der Heinrich-Heine-Universität Düsseldorf Referent: Prof. Dr. Petra Stoerig Koreferent: Prof. Dr. Egon Wanke Tag der mündlichen Prüfung: 2 Juli, 2010 Acknowledgements It is customary, apparently, to fill this section with the names of one’s friends and colleagues, but I have made so many great friends, and met so many intriguing colleagues over the course of my wonderful four year European adventure, that I will never be able to remember them all in the short time I have left to write this section. Here I will address by name only those colleagues whose conversation, collaboration, and companionship have been instrumental to my academic progress here in Nijmegen, and as for the rest, I hope it will suffice to refer to all of you in general, and I hope that you know who you are, and understand what your friendship has meant to me during this period. First and foremost, my supervisor and friend Rolf Kötter, without whom I would most likely never have made the 180° detour that brought me across the Atlantic. Rolf has been a constant source of guidance for me, in many aspects of my work; for starters, he has taught me a new respect for anatomy where my attitude was – let’s say – nonchalant previously. Through him I have met numerous others who are shining stars in their various disciplines, and this has taught me how broad the scope of my chosen field has really become. I am indebted to him in innumerable ways, not the least of which for serving as a mentor and a tower of strength and optimism in the face of a personal situation which I cannot begin to comprehend. Thank-you Rolf. I cannot speak for the Ph.D. tenures of others, because I get the impression that any one experience is truly unique (and such is the attraction to academics, perhaps); but for me this has been a truly educational few years. Rolf contacted me about a position in 2006 on the basis of my neuroscientific background, combined with my computer experience and my expressed desire to move in the direction of computational neuroscience. I had little idea of what I was getting into. In the end, as this dissertation bears out, my research shifted more towards surface modelling and visualization software (with which many of my figures were produced), and a bit of graph theory thrown in for good measure. The forward modelling, which was a prospect both Rolf and myself were looking forward to, will have to wait. Such is the nature of science, and this is another aspect of the learning experience. I have to extend many thanks to Frank-Erik de Leeuw, who approached us with the RUN- DMC data set four years ago, and has been enthusiastic about our collaboration ever since. Through Frank-Erik and my participation in the Donders Center, I have also met some great colleagues and collaborators, including Marcel Zwiers, Anouk van Norden and Lucas van Oudheusden, who were indispensible parts of the (Reid et al., 2010) publication, and Anil Tuladhar, with whom I have been collaborating on the diffusion-weighted imaging project. Egon Wanke at Heinrich Heine in Düsseldorf, and Antje Krumnack, who is now at the Justus-Liebig-Universität Gießen, have been excellent partners on the Shapley value and cortical hierarchies publications. All of you have heightened my interest in scientific research, and I hope we can work together again in the future. My other colleagues in the Neuropi group, Biophysics department, and Donders Center have been equally as indispensible, both academically and socially. Gleb Bezgin collected me at the airport in Düsseldorf, and since that time has been helpful to me in more ways than I can communicate; on top of which he has become a close friend and a constant source of optimism. Ingo Bojak is a fellow researcher, a fine physicist, a solid mathematician, a good friend, and someone who I will perhaps remember most as the person who taught me the meaning of kalauer, which I have never been able to pronounce. Dirk Schubert, Rembrandt i Bakker, Thom Oostendorp, Eva Ludowig, and all of the wonderful students who have graced our lab at some point, have been irreplaceable lunch companions over the past few years, full of humour, intelligence, stories, minor trivia, and South Park anecdotes; I look forward to 12:30 every day. Of course I must thank my parents and the rest of my family as well, who have been.. well, as perfect a family as a guy could ask for. Four years is a long time to be away from each other (especially when your little nephew has grown from a wee baby to an irrepressible bundle of energy), but not once have I felt alone over here, what with the emails and the Skyping and the Easter parcels and the visits. Love you guys, and I really couldn’t have gotten through this thing without you. ii Table of Contents Acknowledgements .................................................................................................................. i Table of Contents ................................................................................................................... iii List of Abbreviations ............................................................................................................ viii List of Figures and Tables ...................................................................................................... x List of Published Figures and Tables .................................................................................... xi Abstract ................................................................................................................................. xii 1. Introduction .................................................................................................... 1 1.1. Overview ........................................................................................................................... 1 1.2. The Neocortex .................................................................................................................. 1 1.2.1. History ...................................................................................................................... 1 1.2.2. Anatomical Methods ................................................................................................ 3 1.2.3. Macroscale Anatomy ................................................................................................ 4 1.2.4. Mesoscale Anatomy ................................................................................................. 4 1.3. Human Brain Mapping .................................................................................................... 6 1.3.1. History and Definitions ........................................................................................... 6 1.3.2. Individual Differences ............................................................................................. 7 1.3.3. Representations ....................................................................................................... 8 1.3.3.1. Textual (coordinate-independent) .................................................................... 8 1.3.3.2. Spatial (coordinate-dependent) ........................................................................ 8 1.3.4. Atlases and Templates ............................................................................................. 9 1.3.4.1. Terminology ..................................................................................................... 10 1.3.4.2. Classical atlases ............................................................................................... 11 1.3.4.3. Probabilistic atlases ......................................................................................... 11 1.4. Brain Connectivity ......................................................................................................... 13 1.4.1. Structural Connectivity ......................................................................................... 13 1.4.1.2. Experimental methods .................................................................................... 13 1.4.1.3. Metadata and databases ................................................................................. 14 1.4.2. Functional Connectivity ........................................................................................ 15 1.4.3. Effective Connectivity ........................................................................................... 16 1.4.3.1. Multiple linear regression .............................................................................. 17 1.4.3.2. Structural equation modelling ....................................................................... 17 1.4.3.3. Dynamic causal modelling .............................................................................. 18 1.4.4. Cortical Hierarchies .............................................................................................. 19 1.4.5. Graph Theoretical Approaches .............................................................................. 20 iii 1.4.5.1. Small worldness .............................................................................................