Imaging correlates of premorbid personality in the frontotemporal dementia-amyotrophic lateral sclerosis spectrum

Abstract Background Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) belong to the same neurodegenerative spectrum. Factors determining phenotypic expression are unknown; however, it is common observation that personality differs between phenotypes: ALS patients tend to display a pleasant and nice attitude, while FTD patients frequently exhibit antisocial behaviours and lack of empathy. We therefore aimed at testing if FTD and ALS patients have different premorbid personalities, and, consequently, different organizations in the brain networks involved in social behaviour and motor function. Method We recruited FTD and ALS patients presenting to Modena University Hospital Neurology Clinics. Patients’ premorbid personality was assessed through the NEO Personality Inventory 3, which evaluates five main personality factors (Neuroticism, Extraversion, Openness, Agreeableness, Conscientiousness). Brain MRI scan including T1‐weighted and resting state fMRI sequences was performed. Data were analysed with voxel‐based morphometry and probabilistic independent component analysis. Result 50 patients (30 FTD, 17 ALS, and 3 FTD‐ALS) were recruited. A significant difference in premorbid personality emerged in the Openness and Extraversion domains, meaning that ALS patients – in their premorbid life – showed higher sociability, loquacity and optimism and were more prone to new experience, ideas, and emotions than FTD patients, respectively. Structural imaging analysis showed a positive correlation between premorbid Neuroticism and grey matter density of the hippocampus bilaterally (left>right) across all patients. Group comparisons of fMRI data showed greater functional connectivity (FC) in ALS compared to FTD patients within the Salience Network (SN) in the right insula, putamen, nucleus accumbens, and the left thalamus. FC within the SN positively correlated with premorbid Openness across all patients. Conclusion Premorbid personality differs between patients with ALS and FTD, and relates to different degrees of FC within the Salience Network. This suggests that premorbid personality may represent a vulnerability marker to the development of specific phenotypes along the FTD‐ALS spectrum.