The sleep EEG envelope: a novel, neuronal firing-based human biomarker

Abstract

Sleep EEG reflects instantaneous voltage differences relative to a reference, while its spectrum reflects the degree to which it is comprised of oscillations at various frequencies. In contrast, the envelope of the sleep EEG reflects the instantaneous amplitude of oscillations at specific frequencies, and its spectrum reflects the rhythmicity of the occurrence of these oscillations. The ordinary sleep EEG and its spectrum have been extensively studied and its individual stability and relationship to various demographic characteristics, psychological traits and pathologies is well known. In contrast, the envelope spectrum has not been extensively studied before. In two studies, we explored the generating mechanisms and utility of studying the envelope of the sleep EEG. First, we used human invasive data from cortex-penetrating microelectrodes and subdural grids to demonstrate that the sleep EEG envelope spectrum reflects local neuronal firing. Second, we used a large database of healthy volunteers to demonstrate that the scalp EEG envelope spectrum is highly stable within individuals, especially in NREM sleep, and that it is affected by age and sex. Multivariate models based on a learning algorithm could predict both age (r=0.6) and sex (r=0.5) with considerable accuracy from the EEG envelope spectrum. With age, oscillations characteristically shifted from a 4-5 second rhythm to higher rhythms. The envelope spectrum was not associated with general cognitive ability (IQ). Our results demonstrate that the sleep envelope spectrum is a promising, neuronal firing-based biomarker of various demographic and disease-related phenotypes.