Altered amygdala structural connectivity and relations to social cognition in frontotemporal dementia

Introduction: The amygdala is critical for social cognition and undergoes profound damage in frontotemporal dementia (FTD). While its atrophy is well documented, changes in its structural connectivity and their behavioral relevance remain unclear. Methods: Using fixel-based analysis and tractography, we examined amygdala connectivity in patients with behavioral variant FTD (bvFTD; n = 21), semantic dementia (SD; n = 19), progressive non-fluent aphasia (PNFA; n = 18), and 28 controls. Associations with empathy and emotion recognition were explored using partial correlations. Results: BvFTD and SD showed marked degeneration of amygdala-associated tracts, while PNFA exhibited subtle left temporal changes. Tractography revealed reduced amygdala connectivity with regions supporting memory, visual, language, semantic, and motor functions, to varying degrees across subtypes. Social cognitive deficits were correlated with amygdala-cerebellum connectivity in bvFTD and with amygdala-hippocampus connectivity in SD. Discussion: These findings were the first to demonstrate subtype-specific patterns of amygdala white matter alteration and their relevance to social cognitive symptoms in FTD.