20th Annual Sleep and Health Benefit

Sleep Spindle Harmonics in Insomnia

Michael Goldstein, PhD

Beth Israel Deaconess Medical Center

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Clinical Implications
Sleep spindle harmonics may provide new insight into pathophysiology of insomnia and non-restorative sleep, such as dysfunction of specific thalamic nuclei that have been found in prior mathematical modeling work to be uniquely linked to spindle harmonics.
Research Narrative

‘Harmonics’ have been observed in EEG data as spectral peaks at multiples of a fundamental frequency associated with an event, so in the case of sleep spindles, a fundamental peak frequency (or ‘1st harmonic’) is say, 14Hz, and so a corresponding harmonic rhythm would be expected at 28Hz. Thus far, there has been very limited application of this idea of spectral harmonics to sleep spindles, even though these patterns can indeed be seen in some existing literature (e.g. Laventure et al., 2018; Lustenberger et al., 2018) and there is growing interest in cross-frequency coupling with spindles, linking them more broadly to beta or gamma EEG. Intriguingly, mathematical modeling work by two different groups (Abesuriya et al., 2014; Ferdousi et al., 2019) found that the harmonic peak, in contrast from the fundamental spindle peak, appears to be more prominently generated specifically by thalamic relay nuclei. Thus, there is the potential that spindle harmonics could provide not only a new EEG biomarker for insomnia, but also a link to specific mechanisms of dysfunction. So, for the first time to our knowledge, we applied this approach to a sample of 15 individuals with insomnia disorder (87% female, 18-32 yrs of age) and 15 matched good-sleeper controls. Consistent with prior studies, we found elevated sleep spindle density and 14-16Hz sigma power, corresponding to fast spindles. Despite no difference in beta/gamma power when averaged across NREM sleep, time-frequency analysis centered on the peaks of detected spindles revealed elevated spectral power surrounding the 28Hz harmonic peak in the insomnia group, especially for spindles coupled with slow waves. We also observed an overall pattern of time-locked delay in the 28Hz harmonic peak, occurring approximately 40 msec after spindle peaks. Furthermore, we observed a 42Hz ‘3rd harmonic’ peak, not yet predicted by the existing modeling work, which was also elevated for insomnia. Consistent with the notion of a thalamic dysfunction in insomnia, prior research (Bridoux et al., 2015) has documented that bilateral thalamic stimulation can induce insomnia in humans. Analyses are ongoing to explore correlations with measures of sleep disturbance, fatigue, etc., however we hope that this innovative lens on EEG data could spark new insights into the pathophysiology of insomnia and non-restorative sleep.

Research Category
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