title: Functional Brain Correlates of Neuropsychiatric Symptoms in Presymptomatic Huntington's Disease: The IMAGE-HD Study.
abstract: BACKGROUND
  Neuropsychiatric disturbances are common in Huntington's Disease (HD) and have been observed in gene-positive individuals several years prior to the onset of motor symptoms. The neural mechanism underpinning the development of neuropsychiatric problems in HD remain unclear.
  
  
  OBJECTIVE
  To investigate whether neural activity during working memory is associated with neuropsychiatric symptoms in premanifest Huntington's Disease.
  
  
  METHODS
  functional magnetic resonance imaging (fMRI) data from Pre-HD far from onset (pre-HDfar, n = 18), pre-HD close to onset (pre-HDclose, n = 17), and controls (n = 32) were analysed. Correlations were performed between fMRI activity in three regions of interest [bilateral dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC)] and neuropsychiatric scores.
  
  
  RESULTS
  In the pre-HDclose group, increased symptoms of obsessive compulsion and depression were associated with decreased blood-oxygen-level-dependent (BOLD) fMRI activity in the right DLPFC and ACC during 1-BACK and 2-BACK working memory conditions. In the pre-HDfar group increased symptoms of depression was associated with decreased right DLPFC BOLD fMRI activity during 2-BACK working memory only.
  
  
  CONCLUSIONS
  The findings suggest that association between neuropsychiatric function and fMRI activity is more readily detectable at higher working memory loads, and becomes more pronounced in those closer to onset.
authors.affiliation: Monash Institute of Cognitive and Clinical Neurosciences/School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.|Life Sciences Computation Centre, Victorian Life Sciences Computation Initiative (VLSCI), Melbourne, Victoria, Australia.
authors.forename: Govinda R
authors.initials: GR
authors.lastname: Poudel
authors.affiliation: Monash Institute of Cognitive and Clinical Neurosciences/School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Shannon
authors.initials: S
authors.lastname: Driscoll
authors.affiliation: Monash Institute of Cognitive and Clinical Neurosciences/School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Domínguez D
authors.affiliation: Monash Institute of Cognitive and Clinical Neurosciences/School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Stout
authors.affiliation: Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Churchyard
authors.affiliation: Department of Psychiatry, Monash University, Clayton, Victoria, Australia.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Chua
authors.affiliation: Monash Institute of Cognitive and Clinical Neurosciences/School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.|Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Egan
authors.affiliation: Monash Institute of Cognitive and Clinical Neurosciences/School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Nellie
authors.initials: N
authors.lastname: Georgiou-Karistianis
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D001523:Mental Disorders / Q000503:physiopathology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D055815:Young Adult
keywords: Huntington’s disease; N-BACK; dorsolateral prefrontal cortex; fMRI BOLD; neuropsychiatric disturbance; working memory