Levels of Error Processing in Huntington's Disease: a Combined Study Using Event-related Potentials and Voxel-based Morphometry

Huntington's Disease (HD) is a neurogenetic disorder accompanied by an atrophy of the striatum and hence of the dopaminergic (DA) system. Neural processes subserving error processing presumably depend on the DA system. We assessed error processing in manifest HD and in presymptomatic HD-gene-mutation-carriers (pHD) with event-related potentials reflecting error processing (the error negativity or error-related negativity and the error positivity derived from a flanker-task. We found a reduction of the Ne in the case of HD compared to pHD reflecting dopamine system pathology. Despite the Ne being reduced in HD, behavioral adaptation was possible. In addition, the error-rates did not differ between the groups. Optimized voxel-based morphometry revealed that grey matter volume in the medial frontal gyrus is correlated with the Ne amplitude in symptomatic patients. In addition, the effect of a Ne-reduction was related to the grey matter underneath the medial frontal gyrus, which is in line with two theories of the Ne. In contrast, the Pe did not differ between the groups, suggesting that the Pe is decoupled from the DA system. Interestingly we found a reduction of a late slow negativity on correct responses, which possibly reflects decreased preparatory processes in HD compared to pHD as induced by the DA alterations in HD. In conclusion a deterioration in error processing in HD compared to pHD is mainly reflected by the Ne. The deterioration might rely on two factors: a neurofunctional and a neuroanatomical.