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The habenula: an under-recognised area of importance in frontotemporal dementia?
  1. Martina Bocchetta1,2,3,
  2. Elizabeth Gordon1,
  3. Charles R Marshall1,
  4. Catherine F Slattery1,
  5. M Jorge Cardoso1,4,
  6. David M Cash1,4,
  7. Miklos Espak1,4,
  8. Marc Modat1,4,
  9. Sebastien Ourselin1,4,
  10. Giovanni B Frisoni2,5,
  11. Jonathan M Schott1,
  12. Jason D Warren1,
  13. Jonathan D Rohrer1
  1. 1 Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK
  2. 2 Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Istituto Centro San Giovanni di Dio—Fatebenefratelli, Brescia, Italy
  3. 3 Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
  4. 4 Translational Imaging Group, Centre for Medical Image Computing (CMIC), University College London, London, UK
  5. 5 Memory Clinic and Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland
  1. Correspondence to Dr Jonathan D Rohrer, Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, 8–11 Queen Square, London WC1N 3BG, UK; j.rohrer{at}

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Behavioural variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterised by atrophy of the frontal and temporal lobes and progressive behavioural and cognitive impairment. Some behavioural symptoms such as craving for food, alcohol or drugs, and hypersexuality are suggestive of abnormal reward processing. The reward circuit is formed by a number of different structures including the orbitofrontal cortex, ventral striatum (in particular the nucleus accumbens), ventral pallidum, anterior cingulate cortex, thalamus, hypothalamus, midbrain and habenula.1 This complex network combines information about motivation, cognitive planning and motor control to develop an appropriate goal-directed response to external environmental stimuli. Many of the brain structures belonging to the reward circuit have been found to be atrophic in bvFTD,2 supporting the theory that impairment of the reward system is an important factor in this disease. Among these structures, the habenula, found medial to the posterior thalamus, is uniquely positioned to participate in reward processing, acting as a convergence point for the limbic system and basal ganglia circuits,3 ,4 and therefore playing a pivotal role in the integration of information required to generate goal-directed behaviours. Despite this key role, it has yet to be investigated in bvFTD.

The aim of this study was to investigate the volume of the habenula in a cohort of patients with bvFTD, hypothesising that it would be smaller than in healthy controls as well as an age-matched group of patients with Alzheimer’s disease (AD) who typically do not show impairment of reward behaviour. We also hypothesised that the habenula would show comparable atrophy to other key areas in the reward network in bvFTD.


Fifteen participants fulfilling criteria for the diagnosis of bvFTD (including eight with a MAPT mutation and four with a pathogenic expansion in the C9orf72 gene) were recruited consecutively from a tertiary referral cognitive …

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