Modelling and quantifying brain connectivity and dynamics with applications in aging and ADHD

Human brain is a complex organ and made up of integrative networks encompassing a large number of regions. These regions communicate with each other to share information involved in complex cognitive processes. Functional connectivity (FC) represents the level of synchronization between different brain regions/networks. Studying functional interactions of the brain creates a platform for understanding functional architecture of the brain as an integrative network and has implications for understanding human cognition. Furthermore, there is evidence that FC patterns are sensitive to different diseases. In addition, age is a significant determinant of intra-/inter-individual variability in the FC patterns. Therefore, key aims for the studies included in this thesis were to apply and develop novel resting-state FC methodologies, with applications in healthy aging and ADHD. Indeed, measures of the brain’s FC may serve as a useful tool to diagnose and predict the course of disease, and useful in developing individualized therapies. Ageor disease-related alterations in the FC could reflect a multitude of factors, including changes in structural connectivity. However, we still have limited knowledge of the emergence of brain dynamics from the underlying anatomy. The interplay between the brain’s structure and dynamics underlies all brain functions. Therefore, in the last study we focused on the systematic modeling of the brain network dynamics. Large-scale computational models are uniquely suited to address difficult questions related to the role of brain’s structural network in shaping functional interactions. In addition, computational modeling of the brain enables us to test different hypotheses without any experimental complication while it provides us with a platform for improving our understanding of different brain mechanisms. A new macroscopic computational model of the brain oscillations for resting-state fMRI was introduced in this thesis, which outperforms previous model in the same class. Then, the effects of malfunctions in different brain regions were simulated and subsequently predicted perturbation patterns were recruited for local vulnerability mapping as well as quantification of hazard rates induced after perturbing any brain region. LIST OF SCIENTIFIC PAPERS I. Salami A, Wåhlin A, Kaboodvand N, Lundquist A, Nyberg L, 2016. Longitudinal evidence for dissociation of anterior and posterior MTL restingstate connectivity in aging: Links to perfusion and memory. Cerebral Cortex. 26(10):3953-3963. doi: 10.1093/cercor/bhw233. II. Kaboodvand N, Bäckman L, Nyberg L, Salami A, 2018. The retrosplenial cortex: A memory gateway between the cortical default mode network and the medial temporal lobe. Human Brain Mapping. doi: 10.1002/hbm.23983. III. Kaboodvand N, Iravani B, Fransson P, 2019. Synergetic configurations of dynamic functional connectivity patterns in ADHD. Manuscript on bioRxiv. doi: 10.1101/734111. IV. Kaboodvand N, van den Huevel M, Fransson P, 2019. Adaptive frequencybased modeling of whole-brain oscillations: Predicting regional vulnerability and hazardousness rates. Network Neuroscience. doi: 10.1162/netn_a_00104. LIST OF ADDITIONAL SCIENTIFIC PAPERS NOT INCLUDED IN THE THESIS I. Nyberg L, Karalija N, Salami A, Andersson M, Wåhlin A, Kaboodvand N, Köhncke Y, Axelsson J, Rieckmann A, Papenberg G, Garrett DD, Riklund K, Lövdén M, Lindenberger U, Bäckman L, 2016. Dopamine D2 receptor availability is linked to hippocampal-caudate functional connectivity and episodic memory. Proceedings of the National Academy of Sciences of the United States of America. 113(28):7918-23. doi: 10.1073/pnas.1606309113. II. Iravani B, Kaboodvand N, Arshamian A, Fransson P, 2019. Different neural dynamics and multiple pathways to ADHD: A Simulation of ADHD brain dynamics and therapeutic effect of nodal excitatory. (In manuscript)