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Social concepts rely on a domain-general anterior-temporal hub and social spokes in ventral prefrontal cortex and insula

Rouse, M.; Garrard, P.; Rowe, J.; Lambon Ralph, M.; Rogers, T.

2026-07-10 neurology
10.64898/2026.07.02.26357102 medRxiv
Show abstract

A long-standing debate surrounding the neural bases of social concepts concerns the role of anterior temporal lobe (ATL). One perspective suggests ATL subregions are dedicated specifically to social knowledge; another suggests the ATLs constitute a domain-general hub for conceptual knowledge, but with graded functional specialisation depending on connectivity to modality specific spokes. The positions have been difficult to adjudicate due to many confounding factors in tests of social and non-social knowledge. We address these challenges via three innovations in assessment of knowledge in frontotemporal dementia (FTD). First, we introduce a new task that controls for several potential confounds. Second, we apply mixed linear models to behavioural data analysis, allowing further control over confounding factors. Third, we extend the mixed-model approach to lesion-symptom mapping, identifying cortical regions where structural pathology yields a disproportionate impairment on social versus non-social knowledge when other factors are controlled. We used these techniques to probe social and non-social knowledge in FTD subtypes: semantic dementia (SD), associated with asymmetric-bilateral ATL atrophy (n=21), and behavioural-variant (bvFTD), characterised by frontoinsular atrophy (n=24). When confounding factors were controlled, people with SD showed an equal impairment for social and non-social concepts, whereas those with bvFTD were disproportionately impaired on social concepts. The differential impairment of social concepts was associated with atrophy in the insula, orbitofrontal and ventromedial prefrontal cortex and other regions implicated in social knowledge generally. The results suggest that the bilateral ATLs constitute a domain-general semantic hub, whereas ventral prefrontal and insula cortex contribute preferentially to knowledge about people.

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