Mapping the relationship between white matter and executive function across the adult lifespan

Student thesis: Doctoral ThesisDoctor of Philosophy


Executive function and some forms of memory have been observed to decline with age. These cognitive declines are often subtle and do not necessarily impede the ability of an individual to lead a perfectly fulfilling and independent life. However, a better understanding of what may influence these small deficits could contribute towards our understanding of what happens when executive dysfunction occurs with greater severity across different patient cohorts. Considerable work has already been done exploring these dynamics regarding cortical and subcortical regions, but white matter correlates are not so well understood. The aim of this study was to examine the relationship between the microstructure of frontal white matter pathways and age-related decline in three key cognitive processes associated with executive function (attention, working memory and planning). 
Methods: 104 healthy participants (18 – 79 years) were recruited for this cross-sectional observational study. Neuroimaging and behavioural measures were collected. Data from a subset of 18 participants was used to establish reliability of manual and semi-automated tractography protocols for the cingulum, corpus callosum, frontal aslant tract (FAT), inferior fronto-occipital fasciculus (IFOF), superior longitudinal fasciculus (SLF) system and uncinate fasciculus in young and older adults. Data a separate group of 86 participants (18 – 77 years) were then analysed to test for age related changes to tract microstructure, task performance and mediation effects of tract microstructure on age-related decline of cognition. 
Results: Overall volume and HMOA measures from manual and semi-automated dissection protocols demonstrated good reliability in both young and older adult age groups except for the third segment of the corpus callosum, the right FAT and right IFOF. Significant age-related declines were observed across all behavioural measures and all tracts except for the posterior segments of the corpus callosum, right cingulum, bilateral SLFI, and left SLF II. Significant task/tract correlations were identified across several different pathways and behavioural measures. Three tracts (left cingulum, left IFOF and left uncinate) demonstrated either a partial or full mediation effect on age-related declines in performance of episodic memory and planning. 
Conclusion: First, results from this study have established that manual and semi-automated dissection protocols are reliable for both young and older adults in a wide range of white matter pathways. Second, this study has described for the first-time ageing trajectories of the frontal aslant tract and SLF system. Lastly, this study has supported the role of the cingulum and IFOF in attention and working memory processes and has highlighted a potentially more prominent role than originally supposed for the uncinate in executive function.
Date of Award1 Feb 2020
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorMitul Mehta (Supervisor) & Andy Simmons (Supervisor)

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