title: 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.
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Alexander Frizell
authors.initials: AF
authors.lastname: Santillo
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Lundblad
authors.affiliation: Lund University Bioimaging Centre (LBIC), Lund University, Lund, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: Geriatric Psychiatry Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Landqvist Waldö
authors.affiliation: Center for Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden.
authors.forename: Danielle
authors.initials: D
authors.lastname: van Westen
authors.affiliation: Center for Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lätt
authors.affiliation: Department of Neurology and Rehabilitation Medicine, Skåne University Hospital, Lund, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Blennow Nordström
authors.affiliation: Geriatric Psychiatry Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.|Department of Psychology, Lund University, Lund, Sweden.
authors.forename: Susanna
authors.initials: S
authors.lastname: Vestberg
authors.affiliation: Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Lindberg
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Nilsson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001519:Behavior; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000502:physiology; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging / Q000473:pathology*; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D066127:White Matter / Q000033:anatomy & histology* / Q000000981:diagnostic imaging