Background Changes in prefrontal brain responses as well as psychiatric deficits are detected in Huntington’s disease (HD) prior to diagnosis.

Aims This study investigated the relationship between psychiatric symptoms and functional brain activity during working memory performance in individuals with pre-symptomatic hd (pre-hd) using the image-hd data set.

Methods/techniques Pre-HD far from onset (pre-hd far, n = 17), pre-hd close to onset (pre-hd close, n = 18), and control (n = 32) groups completed an n-back task (0, 1 and 2-back) during functional magnetic resonance imaging (fMRI). Brain regions of interest included the bilateral dorsolateral prefrontal cortex (dlpfc) and anterior cingulate cortex (acc). Correlations were performed between blood-oxygen-level-dependent (bold) activity in each brain region and scores on a battery of neuropsychiatric inventories, while controlling for age, gender, and accuracy on the n-back task.

Results/outcome For both 1- and 2-back conditions, significant negative correlations were found in the pre-hd close group between neuropsychiatric disturbance and bold activation in both the right dlpfc and acc. During 2-back, a significant negative correlation was found in the pre-hd far group between depression symptoms and right dlpfc bold. For 1-back, no significant correlations were found in the pre-hd far group.

Conclusions These findings suggest that as pre-hd individuals approach onset, increased psychiatric disturbance is associated with decreased functional brain activity, which becomes more wide-spread during higher working memory loads.