Basal ganglia beta oscillations during sleep underlie Parkinsonian insomnia

Abstract

<jats:p>Sleep disorders are among the most debilitating comorbidities of Parkinson’s disease (PD) and affect the majority of patients. Of these, the most common is insomnia, the difficulty to initiate and maintain sleep. The degree of insomnia correlates with PD severity and it responds to treatments that decrease pathological basal ganglia (BG) beta oscillations (10–17 Hz in primates), suggesting that beta activity in the BG may contribute to insomnia. We used multiple electrodes to record BG spiking and field potentials during normal sleep and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in nonhuman primates. MPTP intoxication resulted in severe insomnia with delayed sleep onset, sleep fragmentation, and increased wakefulness. Insomnia was accompanied by the onset of nonrapid eye movement (NREM) sleep beta oscillations that were synchronized across the BG and cerebral cortex. The BG beta oscillatory activity was associated with a decrease in slow oscillations (0.1–2 Hz) throughout the cortex, and spontaneous awakenings were preceded by an increase in BG beta activity and cortico-BG beta coherence. Finally, the increase in beta oscillations in the basal ganglia during sleep paralleled decreased NREM sleep, increased wakefulness, and more frequent awakenings. These results identify NREM sleep beta oscillation in the BG as a neural correlate of PD insomnia and suggest a mechanism by which this disorder could emerge.</jats:p>

The Neurophysiology of Sleep in Parkinson's Disease

“…It remains unknown how this finding compares with control subjects and whether the presence or absence of an identifiable subcortical beta peak in NREM correlates with any sleep‐related symptoms. However, studies in primate models suggest that increased STN beta power in NREM sleep may be associated with insomnia severity 102 . In a 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine primate model, both a decrease in slow oscillatory activity and an increase in beta oscillations in the basal ganglia nuclei were seen during NREM sleep (Fig.…”

Disruption of neocortical synchronisation during slow‐wave sleep in the rotenone model of Parkinson’s disease

“…In the present study, we investigated whether the reduction in SWS was due to a decrease in the number and/or duration of the episodes, but no significant differences between the groups were observed. Also, we demonstrated that rotenone administration altered the power spectrum within different frequency bands, which was also observed with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) administration (Mizrahi‐Kliger, Kaplan, Israel, Deffains, & Bergman, 2020), but not in the 6‐hydroxydopamine (6‐OHDA) animal model (Cavelli et al., 2019).…”

Toward asleep DBS: Cortico basal-ganglia neural activity during interleaved propofol/ketamine sedation mimics NREM/REM sleep activity

“…Moreover, natural nocturnal sleep has been found to be markedly disturbed following surgical procedures 41 . Disturbances of sleep are highly prevalent in basal ganglia-related neurodegenerative disorders, particularly PD [42][43][44] . Enabling a more restful sedation could greatly benefit these patients who already suffer from sleep difficulties.…”

“…The EOG, EMG and EEG were sampled at 2750 Hz. Detailed polysomnography methods can be found here 44 .…”