Amygdala integrity in frontotemporal dementia

Abstract

The amygdala is a highly interconnected subcortical brain region located bilaterally in the medial temporal lobes, playing a critical role in numerous cognitive and socioemotional processes. Damage to the amygdala is consistently observed in frontotemporal dementia (FTD) and is linked to emotional and behavioural disturbances. Yet, the extent of amygdala involvement in different FTD clinical subtypes and its specific relationship with social cognitive impairment remains unclear. Crucially, the amygdala comprises multiple distinct subregions, previous research, however, often considers it as a homogenous structure, overlooking its subregional changes.

This thesis employed cutting-edge neuroimaging techniques to comprehensively investigate the volumetric and structural connectivity changes of the amygdala in FTD, and their clinical implications. Using longitudinal data, Chapter 3 revealed distinct amygdala subregional atrophy trajectories across FTD subtypes. Chapter 4 demonstrated that empathy and emotion recognition deficits in FTD were differentially associated with amygdala subregional volumes, particularly the superficial and centromedial subregions. Chapter 5 applied fixel-based analysis and tractography to identify subtype- specific disruptions in amygdala structural connectivity. Chapter 6 expanded these findings to further show that disrupted structural connections between the amygdala and other brain regions were associated with social cognitive deficits, specific to each FTD subtype. Together, this work demonstrates that amygdala subregional volumes and structural connections are differentially affected across FTD subtypes, and are distinctly engaged in empathy loss and emotion recognition deficits. These findings provide critical insights into disease progression and aid in the development of targeted biomarkers and therapeutic strategies.