Grey and White Matter Clinico-Anatomical Correlates of Disinhibition in Neurodegenerative Disease

Abstract

Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico-anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information-based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insular-orbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the “prefrontal” syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control.

Regional structural hypo‐ and hyperconnectivity of frontal–striatal and frontal–thalamic pathways in behavioral variant frontotemporal dementia

“…Healthy controls underwent the same procedures as the patients, and showed no signs of neurological or psychiatric conditions. Participants included some from previously published works on this cohort (Macfarlane et al, ; Santillo et al, ) where valid MRI data was available.…”

Cognitive inhibition impairments in presymptomatic C9orf72 carriers

“…Clinically, the HSCT has been used in many populations presenting with disinhibition, such as patients with Alzheimer’s disease, Parkinson’s disease, progressive supranuclear palsy, bipolar disorder and finally, patients with cerebrovascular accidents or tumours 3–7. Neuroimaging studies suggest that the HSCT is mainly associated with frontal damage 5–11. In patients with frontotemporal dementia (FTD), the HSCT has also shown to be highly sensitive to cognitive inhibition impairments 8–12…”

“…Neuroimaging studies suggest that the HSCT is mainly associated with frontal damage 5–11. In patients with frontotemporal dementia (FTD), the HSCT has also shown to be highly sensitive to cognitive inhibition impairments 8–12…”

Plasma neurofilament light protein correlates with diffusion tensor imaging metrics in frontotemporal dementia

“…This study explored for the first time the association between plasma NfL levels and DTI metrics in a group of patients affected by bvFTD. We first took a voxel-wise approach to test the extent of the association between DTI metrics and NfL across all white matter structures and then we focused specifically on a subset of tracts of interest, that consistently have been reported to be affected in previous DTI studies on bvFTD (20)(21)(22). The voxel-wise analysis revealed a pattern of negative association between FA and plasma NfL levels that was consistent with the spatial distribution of white matter degeneration in bvFTD as assessed by neuropathology (31) and previous DTI studies (20)(21)(22).…”

“…DTI has already proved to be able to reflect white matter degeneration profiles in FTD (20) and considering the results of previous studies, we aimed to test whether the peripheral concentration of NfL are associated with the degeneration of specific tracts, as appears to be the case in ALS, or if NfL reflects the general level of severity of white matter atrophy in bvFTD, as suggested by the previous studies (12,18). To this end, the association between DTI metrics and NfL levels was investigated both unbiasedly at the whole-brain white matter level and in a region-of-interest analysis focusing on white matter tracts that are known to be involved in the bvFTD pathological process (20)(21)(22)(23). We also included tracts in which degeneration has been reported to correlate with NfL level in the literature, in particular the cortico-spinal tract (14)(15)(16).…”