Grey and white matter correlates of disinhibition in behavioural variant frontotemporal dementia and Alzheimer's disease

Abstract

Behavioural disturbances are common features in neurodegenerative disease but their neural correlates have only recently explored. We investigated the grey and white matter neural correlates of disinhibition via neuropsychological and carer information in a sample of behavioural variant frontotemporal dementia (bv-FTD) and Alzheimer's disease (AD) patients, to establish neuroanatomical markers of thisbehavioural diagnostic feature. We employed the Hayling test of inhibitory functioning and a carer questionnaire (CBI -Cambridge Behavioural Inventory) as measures of disinhibition. Mean and overlap-based statistical analyses on selected test variables were conducted to investigate profiles of performance in bvFTD, AD patients and controls. Hayling and CBI scores were entered as covariates in a grey matter voxel-based morphometry (VBM), as well as in a white matter diffusion tensory imaging (DTI) analysis to determine the grey and white matter neural correlates of disinhibition. Not surprisingly, bvFTD patients showed more disinhibition on both behavioural measures in comparison to AD patients and controls. VBM results revealed that atrophy in orbitofrontal/subcallosal, medial prefrontal cortex and anterior temporal lobe areas covaried with both neuropsychological and carer disinhibition measures. In addition, DTI analysis revealed that white matter integrity fractional anisotrophy (FA) values of the white matter tracts connecting the identified grey matter regions, namely uncinate fasciculus, forceps minor and genu of the corpus callosum, correlated with the disinhibition measures of the Hayling test. To our knowledge,this is the first study identifying the grey and white matter structures related to disinhibition in bvFTD and AD. Further, we find converging evidence across neuropsychological and carer information that the orbitofrontal/subcallosal brain region is critical for inhibiting prepotent responses. Identification of atrophy in this region may allow better clinical identification of disinhibition in neurodegenerative conditions.