β Oscillation during Slow Wave Sleep and Rapid Eye Movement Sleep in the Electroencephalogram of a Transgenic Mouse Model of Huntington’s Disease

Abstract

Study objectivesTo search for early abnormalities in electroencephalogram (EEG) during sleep which may precede motor symptoms in a transgenic mouse model of hereditary neurodegenerative Huntington’s disease (HD).DesignIn the R6/1 transgenic mouse model of HD, rhythmic brain activity in EEG recordings was monitored longitudinally and across vigilance states through the onset and progression of disease.Measurements and resultsMice with chronic electrode implants were recorded monthly over wake-sleep cycles (4 hours), beginning at 9–11 weeks (presymptomatic period) through 6–7 months (symptomatic period). Recording data revealed a unique β rhythm (20–35 Hz), present only in R6/1 transgenic mice, which evolves in close parallel with the disease. In addition, there was an unusual relationship between this β oscillation and vigilance states: while nearly absent during the active waking state, the β oscillation appeared with drowsiness and during slow wave sleep (SWS) and, interestingly, strengthened rather than dissipating when the brain returned to an activated state during rapid eye movement (REM) sleep.ConclusionsIn addition to providing a new in vivo biomarker and insight into Huntington's disease pathophysiology, this serendipitous observation opens a window onto the rarely explored neurophysiology of the cortico-basal ganglia circuit during SWS and REM sleep.

Sleep deficits but no metabolic deficits in premanifest Huntington's disease

“…Our study therefore is the first qEEG study performed during sleep in premanifest and manifest patients with HD and indicates alterations in the NREM‐ and particularly the REM‐dependent oscillatory activity of the brain associated with disease burden in gene carriers. Some of our findings such as the decrease in the 3 to 8Hz range and the increase in the high‐frequency (32–36Hz) range in the early HD group are somewhat similar to findings in transgenic animal studies reporting a progressive decrease in low‐frequency (delta) and increase in high‐frequency (beta–gamma) activity in sleep 11, 12, 58. The REM‐dependent increase in the 1 to 2Hz range is unexpected and could be related to increased REM intensity (density of REM), a hypothesis that remains to be tested.…”

“…These results are intriguing, because EEG activity reflects characteristics of cortical and subcortical neural activity and has the potential to become a biomarker for HD onset and progression in the future 56. Whereas there are a number of quantitative EEG (qEEG) studies of waking brain activity in HD (for a review see Nguyen et al56), there are only a couple of studies looking at spectral features of EEG during sleep, and only in transgenic animal models of HD,11, 12, 14, 57, 58 with no studies in humans. Our study therefore is the first qEEG study performed during sleep in premanifest and manifest patients with HD and indicates alterations in the NREM‐ and particularly the REM‐dependent oscillatory activity of the brain associated with disease burden in gene carriers.…”

Differential modulation of global and local neural oscillations in REM sleep by homeostatic sleep regulation

“…Beta is low in normal REM sleep but increases in animal models of motor diseases (57,58). Gamma is high in REM sleep, and yet its possible involvement in neuronal assembly formation has little experimental evidence.…”

Neurophysiological and Behavioral Effects of Anti-Orexinergic Treatments in a Mouse Model of Huntington's Disease

“…At the behavioral level, HD mice show disturbances in the sleep-wake architecture leading to sleep fragmentation and increased sleepiness during their active period. In the R6/1 model, sleep abnormalities appear as early as 2 months of age, whereas other behavioral deficits, such as cognitive impairments, are mostly still absent [10,[14][15][16]. Motor and cognitive disturbances arise at 3 months of age in this model.…”

“…In addition, electroencephalographic (EEG) recordings in several lines of HD mice have highlighted an excessive synchrony of neural activity in the frequencies between 20 and 40 Hz, which is absent in WT littermates [8,9,12,14,25]. This aberrant oscillatory activity, which is associated with HD, and which we have termed Bbeta activity^(low gamma activity by other authors), reaches, in R6/1 mice, its maximal intensity during the cortical desynchronized brain state of rapid eye movement (REM) sleep.…”