Network approaches to understanding the functional effects of focal brain lesions

Complex network models of functional connectivity have emerged as a paradigm shift in brain mapping over the past decade. Despite significant attention within the neuroimaging and cognitive neuroscience communities, these approaches have hitherto not been extensively explored in neurosurgery. The aim of this thesis is to investigate how the field of connectomics can contribute to understanding the effects of focal brain lesions and to functional brain mapping in neurosurgery. This datasets for this thesis include a clinical population with focal brain tumours and a cohort focused on healthy adolescent brain development. Multiple network analyses of increasing complexity are performed based upon resting state functional MRI. In patients with focal brain tumours, the full complement of resting state networks were apparent, while also suggesting putative patterns of network plasticity. Connectome analysis was able to identify potential signatures of node robustness and connections at risk that could be used to individually plan surgery. Focal lesions induced the formation of new hubs while down regulating previously established hubs. Overall these data are consistent with a dynamic rather than a static response to the presence of focal lesions. Adolescent brain development demonstrated discrete dynamics with distinct gender specific and age-gender interactions. Network architecture also became more robust, particularly to random removal of nodes and edges. Overall these data provide evidence for the early vulnerability rather than enhanced plasticity of brain networks. In summary, this thesis presents a combined analysis of pathological and healthy development datasets focused on understanding the functional effects of focal brain lesions at a network level. The coda serves as an introduction to a forthcoming study, known as Connectomics and Electrical Stimulation for Augmenting Resection (CAESAR), which is an evolution of the results and methods herein.MGH is funded by the Wellcome Trust Neuroscience in Psychiatry Network with additional support from the National Institute for Health Research Cambridge Biomedical Research Centre