Connectivity-driven parcellation methods for the human cerebral cortex

Book excerpt: The macro connectome elucidates the pathways through which brain regions are structurally connected or functionally coupled to perform cognitive functions. It embodies the notion of representing, analysing, and understanding all connections within the brain as a network, while the subdivision of the brain into interacting cortical units is inherent in its architecture. As a result, the definition of network nodes is one of the most critical steps in connectivity network analysis. Parcellations derived from anatomical brain atlases or random parcellations are traditionally used for node identification, however these approaches do not always fully reflect the functional/structural organisation of the brain. Connectivity-driven methods have arisen only recently, aiming to delineate parcellations that are more faithful to the underlying connectivity. Such parcellation methods face several challenges, including but not limited to poor signal-to-noise ratio, the curse of dimensionality, and functional/structural variations inherent in individual brains, which are only limitedly addressed by the current state of the art. In this thesis, we present robust and fully-automated methods for the subdivision of the entire human cerebral cortex based on connectivity information. Our contributions are four-fold: First, we propose a clustering approach to delineate a cortical parcellation that provides a reliable abstraction of the brain's functional organisation. Second, we cast the parcellation problem as a feature reduction problem and make use of manifold learning and image segmentation techniques to identify cortical regions with distinct structural connectivity patterns. Third, we present a multi-layer graphical model that combines within- and between-subject connectivity, which is then decomposed into a cortical parcellation that can represent the whole population, while accounting for the variability across subjects. Finally, we conduct a large-scale, systematic comparison of existing parcellation methods, with a focus on providing some insight into the reliability of brain parcellations in terms of reflecting the underlying connectivity, as well as, revealing their impact on network analysis. We evaluate the proposed parcellation methods on publicly available data from the Human Connectome Project and a plethora of quantitative and qualitative evaluation techniques investigated in the literature. Experiments across multiple resolutions demonstrate the accuracy of the presented methods at both subject and group levels with regards to reproducibility and fidelity to the data. The neuro-biological interpretation of the proposed parcellations is also investigated by comparing parcel boundaries with well-structured properties of the cerebral cortex. Results show the advantage of connectivity-driven parcellations over traditional approaches in terms of better fitting the underlying connectivity. However, the benefit of using connectivity to parcellate the brain is not always as clear regarding the agreement with other modalities and simple network analysis tasks carried out across healthy subjects. Nonetheless, we believe the proposed methods, along with the systematic evaluation of existing techniques, offer an important contribution to the field of brain parcellation, advancing our understanding of how the human cerebral cortex is organised at the macroscale.