Dorsolateral prefrontal activation in Huntington's disease is sensitive to a range of cognitive and behavioral deficits: Cross sectional data from Image-HD.

Abstract

Introduction: Functional integrity of cortico-striatal circuits underlying generalised executive functioning may be compromised by basal ganglia (BG) degeneration during Huntington's Disease (HD). We challenged cortico-striatal function with a shifting response set (SRS) task, and examined associations between the degree of induced neural responses and difficulties with cognition and emotions within HD. Method(s): Thirty-five healthy, 35 matched pre-symptomatic HD (pre-HD) and 30 symptomatic HD (symp-HD) participants completed a computerised SRS task during functional brain scanning (fMRI) at 3 tesla. A 70% performance threshold allowed confident identification of neural activity underpinning SRS (33 control, 32 pre-HD, 20 symp-HD), while associations between neural SRS responses and cognitive-emotional disturbance within the total sample allowed inclusion of dysfunctional responses. Result(s): SRS activated dorsolateral pre-frontal (DLPFC) and cingulate, pre-motor, parietal, and BG regions and deactivated ventromedial pre-frontal cortex (VMPFC). Symp-HD showed greater activation of DLPFC, dorsal cingulate and left anterior insula, and greater deactivation of VMPFC relative to controls, with pre-HD showing similar although less widespread differences relative to controls. Importantly, within symp-HD measures of cognitive and emotional disturbance correlated negatively with DLPFC and dorsal ACC responses, and positively with ventromedial PFC responses evoked during SRS challenge. Conclusion(s): Our findings support previous observations of the contribution of DLPFC, ACC and BG to SRS and indicate that similar behavioural performance in HD requires additional activity within these regions. Critically, our findings suggest that capacity to increase functional brain responses during the transition from pre-HD to symp-HD may be protective against neurocognitive dysfunction.