title: White matter tract signatures of impaired social cognition in frontotemporal lobar degeneration.
abstract: Impairments of social cognition are often leading features in frontotemporal lobar degeneration (FTLD) and likely to reflect large-scale brain network disintegration. However, the neuroanatomical basis of impaired social cognition in FTLD and the role of white matter connections have not been defined. Here we assessed social cognition in a cohort of patients representing two core syndromes of FTLD, behavioural variant frontotemporal dementia (bvFTD; n = 29) and semantic variant primary progressive aphasia (svPPA; n = 15), relative to healthy older individuals (n = 37) using two components of the Awareness of Social Inference Test, canonical emotion identification and sarcasm identification. Diffusion tensor imaging (DTI) was used to derive white matter tract correlates of social cognition performance and compared with the distribution of grey matter atrophy on voxel-based morphometry. The bvFTD and svPPA groups showed comparably severe deficits for identification of canonical emotions and sarcasm, and these deficits were correlated with distributed and overlapping white matter tract alterations particularly affecting frontotemporal connections in the right cerebral hemisphere. The most robust DTI associations were identified in white matter tracts linking cognitive and evaluative processing with emotional responses: anterior thalamic radiation, fornix (emotion identification) and uncinate fasciculus (sarcasm identification). DTI associations of impaired social cognition were more consistent than corresponding grey matter associations. These findings delineate a brain network substrate for the social impairment that characterises FTLD syndromes. The findings further suggest that DTI can generate sensitive and functionally relevant indexes of white matter damage in FTLD, with potential to transcend conventional syndrome boundaries.
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Downey
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Mahoney
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Aisling H
authors.initials: AH
authors.lastname: Buckley
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Golden
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Susie M
authors.initials: SM
authors.lastname: Henley
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmitz
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schott
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK ; Centre for Medical Image Computing, University College London, London, UK.
authors.forename: Ivor J
authors.initials: IJ
authors.lastname: Simpson
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK ; Centre for Medical Image Computing, University College London, London, UK.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Ourselin
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Nick C
authors.initials: NC
authors.lastname: Fox
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Crutch
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Warren
mesh_terms: D000368:Aged; D001284:Atrophy / Q000473:pathology; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D057180:Frontotemporal Dementia / Q000473:pathology* / Q000503:physiopathology*; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D057178:Primary Progressive Nonfluent Aphasia / Q000473:pathology* / Q000503:physiopathology*; D012938:Social Perception; D066127:White Matter / Q000473:pathology*
keywords: Diffusion tensor imaging; Emotion; Frontotemporal dementia; Sarcasm; Social cognition; Voxel based morphometry