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Title: Variability of structurally constrained and unconstrained functional connectivity in schizophrenia
Author: Yao, Ye
ISNI:       0000 0004 7431 6630
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2016
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In this thesis, entropy is used to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional connectivity entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. This is attributed to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. The dataset involved males and females and significant differences were found between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy. In addition, the connectivity between different brain areas provides evidence about normal function and dysfunction. Changes are described in the distribution of these connectional strengths in schizophrenia using a large sample of resting-state fMRI data. The functional connectivity entropy, which measures the dispersion of the functional connectivity distribution, was lower in patients with schizophrenia than in controls, reflecting a reduction in both strong positive and negative correlations between brain regions. The decrease in the functional connectivity entropy was strongly associated with an increase in the positive, negative, and general symptoms. Using an integrate-and-fire simulation model based on anatomical connectivity, it is shown that a reduction in the efficacy of the NMDA mediated excitatory synaptic inputs can reduce the functional connectivity entropy to resemble the pattern seen in schizophrenia. Spatial variation in connectivity is an integral aspect of the brain's architecture. In the absence of this variability, the brain may act as a single homogenous entity without regional specialization. In this thesis, we investigate the variability in functional links categorized on the basis of the presence of direct structural paths (primary) or indirect paths mediated by one (secondary) or more (tertiary) brain regions ascertained by diffusion tensor imaging. We quantified the variability in functional connectivity using an unbiased estimate of unpredictability (functional connectivity entropy) in a neuropsychiatric disorder where structure-function relationship is considered to be abnormal. 34 patients and 32 healthy controls underwent DTI and resting state functional MRI scans. Less than one-third (27.4% in patients, 27.85% in controls) of functional links between brain regions were regarded as direct primary links on the basis of DTI tractography, while the rest were secondary or tertiary. The most significant changes in the distribution of functional connectivity in schizophrenia occur in indirect tertiary paths with no direct axonal linkage in both early (p=0.0002, d=1.46) and late (p=1_10).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QA76 Electronic computers. Computer science. Computer software ; QP Physiology