Kaczmarczyk, Isabella; (2023) The Structural and Pathoconnective Profile of BA4a and BA4p across Neurodegenerative Disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This PhD thesis delves into an in-depth analysis of the structural and pathoconnective intricacies of the anterior and posterior subregions of the Brodmann Area 4 (BA4a and BA4p) in the primary motor cortex (M1) amidst neurodegenerative diseases. The key questions that guide this research include: Do these subregions display distinct patterns during healthy ageing, Traumatic Brain Injury (TBI), Motor Neuron Disease (MND), and Frontotemporal Dementia (FTD)? Are there unique structural changes associated with each of these conditions that can be discerned using advanced imaging techniques? In an effort to answer these, the study harnesses the power of structural and diffusion-based MRI, coupled with the analytical precision of graph theory metrics applied to brain network analysis. By focusing on both global and local structural measures, and structural network measures, the thesis aims to elucidate topographically specific alterations in the brain's motoneuronal networks in relation to ageing, disease onset, and progression. The results reveal distinct neuroplastic processes during ageing and emphasise the importance of considering BA4a and BA4p as structurally and functionally unique regions in future studies. Additionally, the findings indicate that these subregions may be differentially affected by age and sex, and some elements of structural connectivity in BA4a and BA4p behave differently with increasing age. In the context of TBI, the work probes the effects of injury on the structure and connectivity networks related to BA4a and BA4p, identifying new imaging biomarkers for the early assessment of patient susceptibility to neurodegenerative disorders. The findings suggest that BA4p may be more vulnerable to damage and susceptible to TBI than BA4a, contributing to a higher risk of developing neurodegenerative diseases. An in-depth exploration of the structural atrophy and connectivity metrics in patients with MND and FTD is undertaken, with a specific emphasis on the BA4a and BA4p subregions in M1. The results demonstrate evidence of structural atrophy in both subregions and differential responses in the structural connectivity of BA4p compared to BA4a, highlighting the need for further investigation into BA4p's role in MND and FTD. By establishing these physiological links, this research paves the way for understanding the intricate mechanisms behind neurodegenerative diseases. This knowledge can then serve as a foundation for crafting treatment strategies tailored to combat the specific challenges posed by these disorders.

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