E016 The evolution of neural response patterns in Huntington’s disease as assessed by a daily life executive function task shows an inverted U shaped curve declining at the premanifest stage

<h3>Background</h3> The term compensation is often used in fMRI studies of neurodegenerative disorders, since studies often report hyper recruitment in task-related areas ind the disease group when compared with the control group. Then, as the disease progresses, task-related activity decreases and performance deteriorates. This frame of view suggests that disease progression and neural activity are related as a ⋂-shaped curve. Huntington’s disease (HD) data acquired before the onset of clinical manifestations offer an opportunity to study the existence this ⋂-shaped relation. <h3>Methods</h3> We acquired fMRI data while HD participants were engaged in an executive task created in a virtual reality setting that mimics an everyday task in a kitchen. BOLD curves were estimated in ROIs from the executive network. Functional connectivity for the dorsolateral prefrontal cortex was also used to relate with the disease progression. Disease progression was defined as years since the clinical onset of the symptoms (positive values) and the estimated years up to the disease onset (negative values), for the HD group and the premanifest HD group, respectively. <h3>Results</h3> A quadratic regression showing the ⋂-shaped curve in the functional activity was found in the left superior parietal lobule. Significant quadratic regressions were also found for the functional connectivity, showing the ⋂-shaped pattern in the connectivity between the dorsolateral prefrontal cortex and other frontal regions, the posterior cingulate cortex and subcortical regions, as putamen, thalamus and globus pallidus. For the majority of the curves, we found the maximum values of these curves to happen years before the clinical onset. <h3>Conclusion</h3> These results imply that neural decline starts before the motor symptoms arise, and that mechanisms of compensation may hide this decline, while the performance remains unchanged or only with subtle changes in executive function.