Social conceptual impairments in frontotemporal lobar degeneration with right anterior temporal hypometabolism

Abstract

Inappropriate social behaviours are early and distinctive symptoms of the temporal and frontal variants of frontotemporal lobar degeneration (FTLD). Knowledge of social behaviour is essential for appropriate social conduct. It is unknown, however, in what way this knowledge is degraded in FTLD. In a recent functional MRI study, we have identified a right-lateralized superior anterior temporal lobe (aTL) region showing selective activation for 'social concepts' (i.e. concepts describing social behaviour: e.g. 'polite', 'stingy') as compared with concepts describing less socially relevant animal behaviour ('animal function concepts': e.g. 'trainable', 'nutritious'). In a further fMRI study, superior aTL activation was independent of the context of actions and feelings associated with these social concepts. Here, we investigated whether the right superior sector of the aTL is necessary for context-independent knowledge of social concepts. We assessed neuronal glucose uptake using 18-fluoro-deoxy-glucose-positron emission tomography (FDG-PET) and a novel semantic discrimination task which probed knowledge of social and animal function concepts in patients with FTLD (n = 29) and corticobasal syndrome (n = 18). FTLD and corticobasal syndrome groups performed equally poorly on animal function concepts but FTLD patients showed more pronounced impairments on social concepts than corticobasal syndrome patients. FTLD patients with right superior aTL hypometabolism, as determined on individual ROI analyses, were significantly more impaired on social concepts than on animal function concepts. FTLD patients with selective impairments for social concepts, as determined on individual neuropsychological profiles, showed higher levels of inappropriate social behaviours ('disinhibition') and demonstrated more pronounced hypometabolism in the right superior aTL, the left temporal pole and the right lateral orbitofrontal and dorsomedial prefrontal cortex as compared with FTLD patients showing selective impairments of animal function concepts. Combining both FTLD subgroup analyses, based on anatomical and neuropsychological criteria, by using inclusive masks, revealed the right superior aTL as associated with selective impairments of social concepts in both analyses. These results corroborate the hypothesis that the right aTL is necessary for representing conceptual social knowledge. Further, we provide first evidence for the potential importance of conceptual social knowledge impairments as contributing to behavioural symptoms of FTLD.

Figure 1

FDG-PET analysis using SPM5. (A) shows an example of a single case analysis in which hypometabolic clusters in an FTLD patient surviving FDR-corrected P = 0.05 over the volume of the bilateral apriori aTL ROI were overlaid onto his normalized MRI to determine whether anterior temporal cortex inferior or within or superior to the superior temporal sulcus showed hypometabolism. (B) Common areas of hypometabolism in FTLD versus Normal controls and CBS versus Normal controls (inclusive mask at P = 0.005). (C) Hypometabolism in CBS versus FTLD. (D) Hypometabolism in FTLD versus CBS. Areas exceeding a voxel level threshold of P = 0.005 uncorrected, five voxels are displayed. Only regions which additionally survive FWE- or cluster-corrected P = 0.05 over the whole brain or bilateral apriori aTL ROI are reported in Table 1 and discussed in text.

Figure 2

FDG-PET analyses using SPM5. Areas exceeding a voxel level threshold of P = 0.005 uncorrected, five voxels are displayed. Only regions additionally surviving FWE- or cluster-corrected P = 0.05 over bilateral apriori aTL ROI or the whole brain are reported in Table 2 and the text. (A) Analysis 1: FTLD patients with R sup aTL lesion < Normal controls, only regions shown that also show more hypometabolism in FTLD patients with R sup aTL lesion versus FTLD patients without R sup aTL lesion (inclusive mask at P = 0.005) and do not show significant hypometabolism in FTLD patients with no R sup aTL lesion versus Normal controls (exclusive mask at P = 0.005). (B) Analysis 2: FTLD Pat. with social concept selective impairment < Normal controls, only regions shown which are also more hypometabolic in FTLD patients with social concept selective impairments than in those with the reverse dissociation (i.e. animal function concept selective impairments, inclusive mask at P = 0.05) and in which there was no significant hypometabolism for the animal function concept selective impairment group versus Normal controls (exclusive mask at P=.005). (C) Areas common to both analyses displayed at P = 0.005 (Analysis 1 at P =.005 inclusively masked by Analysis 2 at P = 0.05).

Figure 3

Mean scores on the Neurobehavioural Rating Scale in FTLD patients show significant differences between three subgroups (statistics see Table 1) (i) social concept selective impairment group (n = 6), (ii) social concept equal to animal function concept performance group (n = 8), (iii) animal function concept selective impairment group (n = 13). Group 1 (i.e. the social concept selective impairment group) compared with group 3 showed significantly higher total scores (Mann–Whitney U = 13.0, P = 0.02), ‘Disinhibition’ (U = 14.5, P = 0.02) as well as ‘Emotional Withdrawal’ (U = 17.0, P = 0.05) scores. There was no significant difference on ‘Insight/Self-appraisal’ scores (U = 19.0, P = 0.09). *Significant at P = 0.05 for pairwise comparisons