Abstract

Psychiatric symptoms including somatisation are increasingly recognised in frontotemporal lobar dementia (FTLD), especially in conjunction with the recently discovered mutation in the C9orf72 gene. However, the neuroanatomical basis of these symptoms remains to be evaluated. Here we used voxel-based morphometry to analyse the neuroanatomical basis of symptoms of disrupted pain and temperature processing in a cohort of patients with FTLD (n=58, including pathogenic mutations in the C9orf72 and MAPT genes) and Alzheimer's disease (AD, n=20). Symptoms were particularly prevalent in behavioural-variant FTD (71% cases) and semantic dementia (65% cases) and in association with C9orf72 mutations (6/6 cases), but also developed in AD (45% cases). Responses were more blunted in behavioural variant FTD and exaggerated, occurring in conjunction with somatisation behaviour, in semantic dementia. Within the FTLD cohort, symptoms were associated with grey matter loss in a right-lateralised network (posterior thalamus, posterior insula and anterior temporal cortex), key areas implicated in homeostatic processing, and specifically associated with posterior thalamic atrophy in the C9orf72 mutation cohort. We propose a candidate model of how differential disruption to a sensory processing hierarchy can result in abnormal behaviours with the evolution of psychiatric symptoms in neurological disease. The clinical implications of this are discussed.