Increased cognitive functioning in symptomatic Huntington's disease as revealed by behavioral and event-related potential indices of auditory sensory memory and attention

Abstract

Cognitive functions are thought to deteriorate globally in late stages of various neurodegenerative disorders. Here we describe that this general assumption is not justified and fails in Huntington's disease (HD). Presymptomatic gene mutation carriers (pHDs) and healthy controls performed worse compared with symptomatic HDs in an auditory signal detection task. During task performance, behavioral data and event-related potentials (ERPs) [i.e., MMN (mismatch negativity), P3a, and RON (reorienting negativity)] were recorded. Not only behavioral performance but also neurophysiological correlates of auditory sensory memory and attentional reorientation indicate enhanced performance occurring primal in late stages of a neurodegenerative disorder. Increased activity of the NMDA-receptor system, an assumed pathogenic mechanism in HD, might facilitate signal propagation at striatal level that enables more efficient task execution through a winner-take-all process. The results challenge the view that late stage neurodegeneration is necessarily related to a global decline in cognitive abilities in HD. In contrast, selectively enhanced cognitive functioning can emerge together with otherwise impaired cognitive functioning.

Figure 1.

Behavioral data. A, Mean reaction time (error bars indicate SEM) of the control, the presymptomatic (pHD), and the symptomatic (HD) group for the standard and deviant stimuli. B, Mean error rates (error bars indicate SEM) of the control, the presymptomatic (pHD), and the symptomatic (HD) group for the standard and deviant stimuli.

Figure 2.

Neurophysiological data (difference waves). A, Time course of the ERPs. For all electrodes shown, the time course from 200 ms before tone onset (twice) until 1100 ms beyond tone presentation is given. Red lines denote the ERP time course of the HD group, orange lines of the pHD group, and green lines of the control group. B, The scalp topography pattern of the different ERP components (i.e., MMN, P3a, and RON). These are separated for the HD, pHD, and control groups. Note the different scaling of the scalp topography maps.

Figure 3.

Neurophysiological data (original ERPs). A, ERPs on deviant and standard trials at electrodes FC3 and FC4. As can be seen, the N1, which contributes to the modulations of the MMN, does not differ between groups on standard trials, but on deviant trials. Here this was especially the case for the HD-group at electrode FC4, where the MMN was also maximal. B, ERPs on standard trials at electrodes Fz and FCZ. A N2 with clear topography is seen that was stronger in HDs, compared with the other groups. Note that the scaling in A is different from that in B.