Functional brain correlates of neuropsychiatric symptoms in presymptomatic Huntington’s disease: The IMAGE-HD study

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.