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Title: Dynamical complexity of large-scale neurocognitive networks in healthy and pathological brain states
Author: Alderson, Thomas
ISNI:       0000 0004 8504 1388
Awarding Body: Ulster University
Current Institution: Ulster University
Date of Award: 2019
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Contemporary theories suggest that the brain operates in a metastable regime of dynamics in which the tendencies for local areas to integrate and segregate is simultaneously realised. Current theoretical and empirical observations suggest that this behaviour occurs spontaneously through the interaction of local dynamics with underling anatomical connectivity. The metastable regime likely confers important behavioural qualities through the flexible coupling and uncoupling of distributed cortical regions into context-dependent neurocognitive networks. Thus, one of the principle goals of neuroscience, to understand how structure and dynamics interact to generate cognition, may be realised by leveraging the metastable regime of dynamics to link across the interrelated domains of structure, function, and cognition. Accordingly, the proposed approach, grounded in dynamical systems theory, neuroimaging, and theoretical computer modelling, aims to explore how: (1) complex metastable neural dynamics are modulated by cognitive state; (2) structural connectivity confers cognitive flexibility on a fixed network topology through metastable neural dynamics; (3) structural disconnection impacts metastable neural dynamics and how this relates to cognitive performance. The thesis presents findings from three studies. The first uses the theoretical framework of metastable coordination dynamics to explore how cognition arises from the dynamic assembly of local areas into neurocognitive networks. Previous work has suggested that the probability of transitioning between network states is maximised when subjects are not explicitly engaged in a task. Contrary to expectations, metastability between networks was higher during task engagement than during periods of 'cognitive rest'. Task-based reasoning was characterised by dynamic stability in sensory regions and dynamic flexibility in regions devoted to cognitive control. Critically, this dynamic flexibility appeared to confer superior problem solving ability in tests of fluid intelligence. The second study leverages an example of incipient neurodegeneration, mild cognitive impairment (MCI), to test the essential proposition that cognitive deficits are linked to structural disconnection in the brain's largescale network architecture. Accordingly, this study examines the structural connectivity between thalamus and key regions of the cortex implicated in 'cognitive rest': the default mode network (DMN). Abnormal structural connectivity and altered patterns of causation were identified in this 'thalamo-DMN' loop and, crucially, these deficits were linked to memory recall. Taken together, these findings provide new insight into the causal pathways underlying DMN dysfunction in MCI and Alzheimer's disease (AD) and provides preliminary evidence that AD represents a failure of circulating information consistent with its status as a 'disconnection syndrome'. The third and final study uses a joint theoretical and empirical approach to examine how dynamics and cognitive ability are shaped by the macroscopic connectivity of the brain. Accordingly, this study investigates the asymptotic decline of neural metastability in an example of structural disconnection, AD, and its prodrome, MCI. Whole-brain computer modelling mechanistically linked reduced metastability to anatomical disconnection. Moreover, metastability was linked to features of the brain's structural topology. Crucially, empirical estimates of metastability were linked to global cognitive performance. Taken together, these findings suggest a critical linkage between metastability, cognition, and network topology in the damaged or diseased brain. Overall, these three studies provide insight into the dynamic principles by which cognitive architecture is organised and suggest that the metastable regime of dynamics offers considerable potential as a theoretical and conceptual framework for linking structure, function, and cognition in the human brain.
Supervisor: Maguire, Liam ; Coyle, Damien Sponsor: DEL
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Metastability ; Resting state ; fMRI ; DTI ; Neural dynamics ; Whole-brain computer modelling