Neuroanatomical profiles of personality change in frontotemporal

characteristics that uniquely influences an individual’s cognition, motivation and behaviour, is a complex and challenging concept. Even the definition and quantification of personality traits is problematic. The ‘five factor’ model of personality has met with wide acceptance due to its robustness across ages, genders and cultures. According to this model, personality results from the stable balance of five key traits, extraversion, agreeableness, conscientiousness, neuroticism and openness to new experiences, often called the ‘big five’. However, although this model suggests a framework for the study of personality, the neurobiological basis of personality remains poorly understood. Personality traits are likely to be mediated by distributed brain networks and commonly implicated areas include prefrontal, anterior cingulate and orbitofrontal cortices. These areas are likely to play a key role in the cognition of interpersonal and other social behaviours. Frontotemporal lobar degeneration (FTLD) is an important cause of young-onset dementia that frequently manifests with progressive behavioural abnormalities and social dysfunction, as recognised in consensus diagnostic criteria. As acknowledged in current definitions, behavioural characteristics and their modulation in social contexts powerfully influence the maintenance of personality, implying that significant or persistent behavioural abnormalities may alter personality structure. Although much work in FTLD has focused on particular aspects of disturbed behaviour, there is evidence that more pervasive changes in personality are indeed a hallmark of diseases in the FTLD spectrum. From a neurobiological perspective, FTLD therefore presents an opportunity to assess the critical brain substrates that maintain a stable personality structure. Studies in healthy individuals have revealed neuroanatomical substrates overlapping with brain regions that are selectively damaged in FTLD. Whereas behavioural change has been linked with structural brain damage in Alzheimer’s disease and FTLD, particularly the subgroup with right temporal lobe atrophy, studies assessing personality change per se are fewer. Agreeableness in FTLD has been correlated with changes in the volume of orbitofrontal cortex, whereas traits clustered according to properties such as affiliation and agency have been shown to correlate with patterns of distributed atrophy across a range of neurodegenerative diseases. However, little information is available concerning the cerebral correlates of longitudinal change in particular personality traits in neurodegenerative disease. From a clinical perspective, it has been shown that profiles of personality change can distinguish neurodegenerative diseases; analysis of personality change might potentially provide tools for early diagnosis of particular neurodegenerative diseases, and FTLD in particular. Here we investigated cerebral correlates of longitudinal change in key personality traits in FTLD (as measured on a validated caregiver questionnaire) using voxel-based morphometry (VBM). We hypothesised that change in particular personality traits in FTLD would correlate with distinct profiles of brain atrophy and these profiles would overlap frontotemporal networks previously implicated in social cognition.