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

PLoS One. 2016 Oct 10;11(10):e0164122. doi: 10.1371/journal.pone.0164122. eCollection 2016.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Behavior
  • Case-Control Studies
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiology
  • Diffusion Tensor Imaging
  • Female
  • Gray Matter / anatomy & histology*
  • Gray Matter / diagnostic imaging
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / diagnostic imaging
  • Neurodegenerative Diseases / pathology*
  • Neuropsychological Tests
  • Severity of Illness Index
  • White Matter / anatomy & histology*
  • White Matter / diagnostic imaging

Grants and funding

The work was supported by government funding of clinical research within NHS Sweden (ALF), The Basal Ganglia Disorders Linneaus Consortium (BAGADILICO), MultiPark, The Fromma Foundation, The Swedish Alzheimer Foundation, The Thureus´s Foundation, The Konsul Thure Carlssons Minne Foundation, The Trolle-Wachtmeister Foundation for Medical Research, The Märta Lundqvist Foundation, and the Swedish Research Council Grant No 521-210-3034. The financial sponsors did not have any role in the study design, in the collection, analysis and interpretation of data, in the writing of the report, nor in the decision to submit the article for publication.