TESI DOCTORAL UPF / 2012 Brain activity during rest A signature of the underlying network dynamics Joana R. B. Cabral Director de la tesi Prof. Gustavo Deco Department of Information and Communication Technologies Universitat Pompeu Fabra Barcelona, May 2012 In memory of the ones who dedicated their life to neuroscience. Acknowledgments A fulfilled life is reached when you make an effort to follow your dreams. During the spring of 2007, at the age of 23, driven by an insatiable eagerness for learning more about the fascinating field of neuroscience, I visited prof. Gustavo Deco in Barcelona with the possibility of pursuing my PhD studies in Theoretical and Computational Neuroscience. From that first day, Gustavo has given me unconditional support and motivation. Over the past five years, he has guided me through the paths of a research life always with a smile. Above all, he taught me how to do science, by listening to my ideas and telling me to explore them and prove them. For this and for all, I wish to thank him not only for supervising me, but also for inspiring me. My aims to engage in a neuroscientist’s career appeared while performing fieldwork for my Master’s thesis at the Lisbon’s Psychiatric Hospital with Prof. Mario Secca and Dr. Alberto Leal, with whom I got familiar with the unresolved mysteries of brain dynamics and particularly interested about the alterations observed in brain activity of subjects diagnosed with mental illnesses. I want to thank them for that and for supporting my PhD grant application. This PhD would have hardly been possible without the wonderful sponsoring from the Portuguese Foundation of Science and Technology and the European Social Fund, to which I am grateful. During my PhD research, I worked in close collaboration with several people to whom I am in debt. I would like to start with Etienne Hugues, to whom I want to express my gratitude for patiently guiding me through the complicated mathematical concepts of nonlinear dynamics, for carefully reviewing my simulation codes and for helping me understand the complex dynamics emerging from the simulations. i I wish to acknowledge Prof. Olaf Sporns, the “father” of the Connectome, with whom I had fruitful discussions, and who provided outstanding human structural and functional connectivity data, a key ingredient for this work. Likewise, I cannot fail to thank Prof. Rolf Kötter, who passed away in 2010 during our collaboration, for his contribution with the macaque neuroanatomical connectivity. During the spring of 2011, I had the amazing opportunity to undergo an internship at the Psychiatry Department of the University of Oxford. I will be eternally grateful to Prof. Morten Kringelbach for receiving me with open arms in his lab (as well as Christine, Katie, Tim and Maria), for believing in my capacities from the first moment and for providing excellent Connectomes from a large sample of students. During my stay in Oxford, I had the privilege to work in close collaboration with Prof. Mark Woolrich, Henry Luckhoo, Morten Joensson and Hamid Moseni who I want to thank for the outstanding data provided. The work presented in chapter III was part of the Brainsync, an European FP7 research project leaded by Prof. Maurizio Corbetta, in joint collaboration with the research groups of P. Fries, A. Engel, G. Orban, J.-P. Lachaux, J. Driver and M. Palus, with whom I had the opportunity to share ideas in the meetings in Barcelona and in Prague. During this project, I spent a week in the MEG lab in Chieti (ITAB), where I was warmly received by Stefania Della Penna, Francesco de Pasquale and Laura Marzetti, and I wish to thank them for introducing me to state-of-the-art analytic techniques of MEG data. Finally, I would like to thank the people who indirectly contributed for this work through fruitful discussions about 1) the Kuramoto model, in particular Prof. Murray Shanahan, Prof. Michael Breakspear and Ernest Montbrió, and 2) graph theory, namely Mikail Rubinov and Mary-Ellen Lynall. Apart from direct collaborations for this work, I would like to express my gratitude to all my colleagues at the Universitat Pompeu Fabra, with a special note to Larissa Albantakis and Yotta Theodoni, my best companions through the PhD, to the secretaries for all the help and care, and to all the members of the new Center for Brain and Cognition. ii Outside academia, but not less important, I would like to start by acknowledging the ones who brought me to life, Carlos and Ni, who stimulated my brain since early ages by feeding me with puzzles and quizzes, who gave me unconditional love and support in every moment of my life, and provided me the tools and inspiration to become the person I am today. I also want to thank my lovely little (almost twin) sister Catarina, with whom I shared most of my life, and Tomás, who became my brother in law during this PhD. I want to thank all my large family, especially my grandmother, who I still tenderly call Bábá. The most important source of support in my PhD came from a very special person: someone who listened carefully to incomprehensible theories, who gave me strength and motivation, who constantly lifted me up, and who makes me believe that, one day, I will uncover all the mysteries in the brain. Merci Duarte. It is by the side of someone like this that life should be lived. As I say in the beginning, ‘A fulfilled life is reached when you make an effort to follow your dreams’, and if my previous dream was to become a neuroscientist, now that I am on track, I have a new one to follow. I also want to thank my best friends, for always being there despite the distance, which I will cite in alphabetical order to avoid conflict: Babs, Beni, Joana, Juju, Maggie, Mariana AL, Mariana HV, Matilde, Sara, Sofia and Xica. You are all tremendously important in my life. Also, a special thank you to Francisca Figueiras, who came with me to Barcelona in May 2007 to visit research labs and who is depositing the PhD thesis on the exact same day as me, and Joana Mesquita. Finally, I wish to acknowledge the Members of the Committee, for their time and interest, and all the future readers of this thesis. I hope you enjoy reading it as much as I did writing it. iii iv Abstract Neural activity in the brain exhibits complex oscillatory phenomena that can be compared with the ones observed in artificial network models of coupled oscillators. In particular, neuroimaging studies of brain activity during rest have reported slow spatiotemporally organized fluctuations and correlated band-limited power modulations. Simultaneously, theoretical works on the area of physics have reported similar dynamic behaviours using simple models of coupled oscillators with intermittent modular synchronization. In this work, for the first time, we use models of phase oscillators in networks inspired in the brain’s wiring architecture. Results show the spontaneous emergence of a dynamics similar to the one observed experimentally. In addition, this correspondence is quantitatively comparable to neuroimaging data, which is suggestive of general integrative processes underlying cognition. Furthermore, we propose that altered brain activity observed in some psychiatric diseases might originate from structural disconnections, which affect the cooperative behaviour of coupled cortical regions. v vi Resumen La actividad neuronal en el cerebro exhibe complejos fenómenos oscilatorios similares a los que se observan en modelos de redes artificiales con osciladores acoplados. Por un lado, estudios de neuroimagen sobre la actividad cerebral durante el reposo han demostrado la presencia de fluctuaciones lentas estructuradas y modulaciones de potencia a distintas frecuencias. Simultáneamente, se han publicado estudios teóricos en el ámbito de la física que muestran dinámicas similares usando osciladores acoplados con sincronización modular intermitente. En este trabajo, por primera vez, se usan modelos de osciladores de fase en redes inspiradas en la arquitectura real del cerebro. Los resultados muestran la aparición espontánea de una dinámica similar a la observada experimentalmente. Además, esta correspondencia es comparable cuantitativamente con datos de neuroimagen, lo que sugiere procesos generales de integración subyacentes a la cognición. Por otra parte, se propone que la actividad cerebral alterada observada en algunas enfermedades psiquiátricas podría tener su origen en desconexiones estructurales que afectarían el comportamiento cooperativo de regiones corticales acopladas. vii viii Preface How cognition unfolds from the physical structure of the brain is still one of the leading unresolved mysteries of science. For its complexity, this investigation has been progressively extended from the medical field to theoretical sciences such as physics and mathematics. In particular, the approach of the brain as a complex dynamical system, where multiple units, be they neurons or cortical areas, interact with each other in a cooperative manner to integrate and process information, has only recently begun to be explored. It is believed we are only now engaging in the era of Neuroscience. Constant innovation in neuroimaging techniques allows us to explore non-invasively brain structure and dynamics at increasingly higher spatial and temporal resolution. Every year, more than thirty thousand neuroscientists meet together to discuss and share the latest advances in Neuroscience at the Society for Neuroscience annual meeting. Furthermore, thanks to efficient publication mechanisms and to the immediate availability of literature in the internet, the cooperative work of neuroscientists from all over the world has increased exponentially. In the same way as neurons build cognition through cooperative processes, I expect the cumulative discoveries about the brain will lead, hopefully soon enough, to a complete understanding of the brain. This thesis focuses on ongoing activity of the brain at rest, i.e., under no stimulation and in absence of any physical or mental task.