Examining neurophysiological markers of apathy and processing speed in late premanifest and early-stage manifest Huntington’s disease

Objective To find sensitive biological markers of non-motor symptoms in Huntington’s disease (HD), which are essential for the development and assessment of novel treatments. Methods We used resting state EEG to examine differences in oscillatory activity (analysing the isolated periodic as well as the complete EEG signal) and functional connectivity in 22 late premanifest and early stage people with HD and 20 neurotypical controls. We then assessed the correlations between these neurophysiological markers and clinical measures of apathy and cognitive functioning. Results Significantly lower theta and greater delta resting state power was seen in the HD group, as well as significantly greater delta connectivity. There was a significant positive correlation between theta power and processing speed, however there were no associations between the neurophysiological and apathy measures. Conclusions We speculate that these changes in oscillatory power and connectivity reflect ongoing, frontally concentrated degenerative and compensatory processes associated with HD. Significance Our findings support the potential utility of quantitative EEG as a proximate marker for non-motor symptoms in HD. Highlights We examined EEG oscillatory power and functional connectivity as a marker of non-motor symptoms in HD. The HD group had lower theta power, higher delta power and connectivity, and theta power was correlated with processing speed. Our findings support the use of quantitative EEG metrics as potential non-motor symptom markers for clinical research in HD.