Levels of error processing in Huntington's disease: a combined study using event-related potentials and voxel-based morphometry

Abstract

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.

Figure 1

Grand averages of the Ne and CRN/Nc separated for the HD and pHD group at electrode Fz. Negativity is plotted downward, positivity is plotted upward. Shortly after the response, set at 0 ms, negative deflections are seen. It is shown that the Ne of the HD‐group (black line) is attenuated compared to the pHD‐group (blue line). No group differences in the CRN/Nc (green and grey line) are seen. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 2

Grand averages of the Pe and the negativity related to corrected responses separated for the HD and pHD group at electrode Pz. Negativity is plotted downward, positivity is plotted upward. The response is set at 0 ms. In a time window from 200 till 500 ms a positive deflection in error trials (Pe) is seen in the HD (black line) and pHD group (blue line) not differing between the groups, despite the maps show a different topography. For correct reactions group differences are seen. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 3

Differences in grey matter volume between symptomatic and asymptomatic HD patients as detailed in Table II. (independent‐sample t‐test, P < 0.001 uncorrected for multiple comparisons, k = 20). The color bar represents T‐values. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 4

The grey matter volume in the right medial frontal gyrus (BA 9) revealed a significant correlation with the Ne potential over electrode FZ for the HD‐group. The results are displayed on the averaged brain of all patients included in this study (N = 21). The color bar represents T‐values. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]