To CRUNCH or not to CRUNCH: Task Difficulty Affects Functional Brain Reorganisation during Visuospatial Working Memory Performance in Premanifest Huntington's Disease

Presymptomatic Huntington9s disease (pre-HD) individuals tend to increase functional brain activity to compensate for HD-related brain anomalies. We used a quantitative model of compensation, known as the CRUNCH (Compensation-Related Utilization of Neural Circuits Hypothesis) to explicitly characterise compensation in pre-HD. We acquired functional magnetic resonance imaging (fMRI) data (n = 15 pre-HD; n = 15 controls) during performance of an 18-minute fMRI visuospatial working memory task with low, intermediate-1, intermediate-2, and high memory loads. Consistent with the CRUNCH prediction, pre-HD individuals showed decreased fMRI activity in left intraparietal sulcus at high memory load, compared to healthy controls who showed increased fMRI activity in left intraparietal sulcus at high memory load. Contrary to the other CRUNCH prediction, the pre-HD group did not show compensatory increase in fMRI activity at lower levels of memory loads in left intraparietal sulcus. Our findings provide partial support for the validity of CRUNCH in pre-HD.