Grey and white matter correlates of behavioural disinhibition assessed under semi-ecological conditions in behavioural variant frontotemporal dementia.

Abstract

Behavioural variant frontotemporal dementia (bvFTD) is partly characterised by inhibition disorders. Neural correlates of disinhibition being poorly known, we aim to identify grey and white matter impairments associated to behavioural disinhibition. We assess behavioural disinhibition in a semi-ecological setting, noting occurrences of 16 behaviours - derived from clinical criteria of bvFTD - related to compulsivity, impulsivity or social disinhibition, in a population of 20 bvFTD and 20 healthy controls (HC). Subjects also undergo an MRI. In this study, voxel-based morphometry and diffusion tensor tractography (DTI) are used to investigate grey and white matter changes in bvFTD patients compared to HC. Grey matter atrophy and DTI metrics - fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) - are then correlated to behavioural disinhibition scores. Grey matter analysis was conducted on 15 bvFTD and 18 HC. Results mainly show an alteration of frontal and anterior temporal regions as well as subcortical regions (e.g., thalamus) in bvFTD patients compared to HC. Social disinhibition is correlated with a huge atrophy of the frontotemporal regions and of the cingulate cortex, while compulsivity and impulsivity are associated to smaller areas of the orbitofrontal and temporal regions. Based on these results, white matter analysis was conducted on 10 bvFTD patients and 11 HC. Results show a significant decrease of FA and increase of RD in the cingulum, the forceps minor (FM) and the uncinate fasciculus (UF) in bvFTD patients. In addition, patients show a significant increase of MD in the FM and the UF, as well as a significant increase of AD in the FM and right UF. Among bvFTD patients, compulsivity is associated to a weaker integrity of the cingulum while social disinhibition is correlated to alterations of the left UF. On the contrary, impulsivity is correlated with greater integrity of the bilateral uncinate. The cingulum is already known to be impaired in obsessive-compulsive disorder and UF impairments are related to behavioural and social disinhibition. Furthermore, positive correlation between impulsive behaviours and UF integrity are already reported, which is consistent with our findings based on a semi-ecological assessment of behavioural disinhibition.