Brain networks in healthy ageing and psychiatric conditions.

Abstract

Conceptualising the human brain upon its large-scale interactions has led to the realisation of integrative neural processes as critical to cerebral functioning. This thesis sought to elucidate the brain patterns of functional integration and segregation that are associated with the cognitive and behavioural changes in healthy ageing and psychiatric conditions. The network features expressed with age-related cognitive changes are poorly understood within a healthy older population. Th e brain network disturbances in individuals at high-genetic risk for bipolar disorder (BO) are also unknown. Study 1 (Chapter 2) leveraged advances in diffusion-tractography to derive the features of structural brain networks in healthy older adults. The integrative features of the core backbone are observed in the connectomes of both young and older adults, reflecting ongoing patterns of efficient brain communication. Study 2 (Chapter 3) leveraged multivariate analysis to examine in healthy older adults the complex relations between age, functional connectivity, and cognitive performance. A functional sensorimotor subnetwork was identified whose expression is opposed by age against core cognitive processes such as attention and processing speed. Modifiable factors such as increased education are associated with distinct functional networks. Lastly, study 3 (Chapter 4) investigated the structural networks in patients and also unaffected relatives at high-genetic risk for BO. Relative to matched-controls, alterations to fronto-limbic circuits housing key emotional and cognitive centers were identified within both patient and high-risk groups. The present works illustrate the expression of large-scale brain network features are associated with phenotypic differences in healthy older adults and psychiatric conditions. Inter-individual differences in the integration of cerebral information processing is strongly implicated here for the respective changes in functioning: Sensorimotor networks supporting lower-order processes are most sensitive to healthy ageing, whilst fronto-limbic disturbances in patient and high-risk groups are consistent with the emotional liability in BO. The integrative features of key-hub regions are also demonstrated throughout these studies as critical to brain communication capacity. This thesis hence contributes as an important body of work in our ability to understand and predict human brain functioning and behaviour.