title: Impaired self-other differentiation in frontotemporal dementia due to the C9ORF72 expansion.
abstract: BACKGROUND
  An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as an important cause of frontotemporal dementia and motor neuron disease; however, the phenotypic spectrum of this entity and its pathophysiologic basis have yet to be fully defined. Psychiatric features may be early and prominent, although a putative cortico-thalamo-cerebellar network has been implicated in the pathogenesis of the clinical phenotype. Differentiation of self from others is a core cognitive operation that could potentially link network disintegration with neuropsychiatric symptoms in C9ORF72-associated frontotemporal dementia.
  
  
  METHODS
  We undertook a detailed behavioral analysis of self-other attribution in a 67-year-old male patient with behavioral variant frontotemporal dementia (bvFTD) due to the C9ORF72 expansion by using a novel paradigm requiring differentiation of the effects of self- and non-self-generated actions. The patient's performance was assessed in relation to two older male patients with bvFTD not attributable to the C9ORF72 expansion and four healthy older male subjects.
  
  
  RESULTS
  Compared with the healthy control group, the patient with the C9OFR72 mutation showed a deficit of self-other differentiation that was disproportionate to his otherwise relatively indolent clinical phenotype. The performance of the other patients with bvFTD was similar to that of healthy subjects.
  
  
  CONCLUSIONS
  We propose that impaired self-other differentiation is a candidate mechanism for neuropsychiatric decline in association with the C9ORF72 expansion. We offer this preliminary observation as a stimulus to further work.
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Downey
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Mahoney
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Martin N
authors.initials: MN
authors.lastname: Rossor
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Crutch
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Warren