Multimodal semantic knowledge of emotion concepts in frontotemporal dementia

Recent work has delineated the semantic behavioral variant of frontotemporal dementia (sbvFTD; or right temporal variant of FTD, which is thought to preferentially impair semantic knowledge for emotional concepts. However, this proposed core feature has not yet been empirically validated, and no clinical tool exists to assess it. Establishing reliable markers is essential to clinically differentiate sbvFTD from behavioral variant FTD (bvFTD), which is critical given their overlapping behavioral symptoms but divergent underlying pathologies. Furthermore, contrasting sbvFTD with semantic variant primary progressive aphasia (svPPA) can advance our understanding of semantic memory, revealing how the right and left anterior temporal lobes (ATLs) support emotion- versus tool-related knowledge, highlighting the graded, lateralized organization of the semantic system.

We studied 15 patients with sbvFTD, 15 with svPPA, 18 with bvFTD, and 37 healthy controls. A novel multimodal semantic battery, the Fear and Spider Test (FST), which assesses tool- and emotion-related concepts across word-based semantic associations, picture-based semantic associations, and sound-to-picture matching, was administered. Stimuli were matched on psycholinguistic and perceptual features, and emotional items were drawn from multicultural facial expressions validated with the Facial Action Coding System. Neural correlates of semantic performance were investigated using voxel-based morphometry.

As expected, patients with both sbvFTD and svPPA showed greater deficits in all semantic tasks compared to controls and bvFTD, and bilateral anterior temporal lobe (ATL) volumes were broadly associated with performance across all semantic tasks. Interactions between modality and categories were necessary for the emergence of differences between sbvFTD and svPPA and right and left ATL atrophy: performance on the Words-Tools condition was more impaired in svPPA and correlated with left ATL volume, while performance on the Pictures-Emotions condition was more impaired in sbvFTD and correlated with right ATL volume.

The FST provides the first clear dissociation of sbvFTD from bvFTD, a distinction of critical clinical importance given their divergent pathological substrates and the absence of frontotemporal lobar degeneration specific biomarkers. The study also refines our understanding of semantic memory: contrasting sbvFTD with svPPA reveals complementary roles of the right and left ATLs in supporting emotion and tool knowledge, underscoring the graded, lateralized organization of the semantic system.