A magnetic resonance imaging (MRI) investigation into the effects of ageing on the functional and structural connectivity of the brain

Ageing in the absence of disease is associated with reduced cognitive function. Cognitive function depends on the integrated operation of large-scale distributed brain networks. In this thesis I use structural and functional magnetic resonance imaging to test the hypothesis that age related cognitive decline arises from disruption to the integrated operation of large-scale networks, and the disrupted operation of these networks is associated with structural disconnection to white matter tracts. There are five studies presented in this thesis. The first study demonstrates that from middle-age onwards there are reduced grey and white matter volumes and increased damage to widespread regions of white matter, suggesting disconnection across many neuronal networks. In the second study, analysis of thalamo-cortical connectivity reveals a reduced volume of thalamo-frontal projections with age that follows an allometric scaling law and predicts a decline in executive function. Next, I show that disruption in functional and structural connectivity within large-scale networks that occupy regions within the frontal lobe predict age–related differences in cognition. Reduced functional connectivity at the level of the frontal lobe within these networks is associated with micro-structural damage to widespread white matter pathways, suggesting that white matter damage in remote networks can disrupt interconnectivity within other networks. I then investigate the effect of age-related white matter damage on large-scale network function and behaviour using a response inhibition task. I demonstrate that older adults fail to deactivate the Default Mode Network during response inhibition. Failure to deactivate the DMN is associated with impaired inhibitory performance. Regulation of the DMN is predicted by the structural integrity within a remote brain network, the Salience Network. This work identifies DMN dysfunction as an underlying factor in cognitive deficits associated with increasing age, and confirms that white matter damage interrupts the interaction between large-scale networks in the ageing brain.Open Acces