EEG Spectral Analysis in Primary Insomnia: NREM Period Effects and Sex Differences

TLDR: Women with PI, but not men, showed increased high-frequency and low-frequency EEG activity during NREM sleep compared to GSC, particularly in early NREM periods, which may moderate quantitative EEG differences between PI and GSC.

Abstract: THE ETIOLOGY AND PATHOPHYSIOLOGY OF INSOMNIA ARE UNKNOWN, BUT IT IS OFTEN CONSIDERED TO BE A DISORDER OF INCREASED PHYSIOLOGICAL and cognitive arousal.1–3 Evidence for physiological arousal includes elevated resting metabolic rate,4,5 increased heart rate and sympathovagal tone as indicated by heart rate variability (HRV),6,7 increased cortisol secretion in the evening and early sleep hours,8,9 increased beta EEG activity during NREM sleep,10–14 and increased glucose metabolic rate during NREM sleep.15 Evidence for increased arousal defined in cognitive terms is found in the pre-sleep thoughts of insomnia patients compared to good sleepers,16–19 which are often described as “racing,” unstoppable, and sleep-focused. Contemporary models of the pathophysiology of insomnia suggest that, in individuals predisposed on the basis of genetic or affective factors, the acute experience of sleep difficulty leads to a positive feedback loop of selective attention, conditioned arousal, poor sleep, and impaired waking function.20–23 Of the various indicators of hyperarousal in insomnia, quantitative EEG characteristics have been studied most carefully, usually through the use of power spectral analysis of the sleep EEG. Particular attention has been focused on high frequency activity in the range of 16–32 Hz, or “beta activity,” which is thought to reflect a form of cortical activation. This interpretation is based on waking EEG studies in healthy adults, where even higher frequency EEG activity (in the “gamma” range of 30–100 Hz) is thought to represent an analog of sensory processing, focused attention, learning, or memory.13,24–26 Most insomnia studies have focused on quantitative EEG obtained during NREM sleep, as opposed to REM sleep, in part because phasic eye movements and muscle activity can lead to EEG artifacts during REM, and in part because there is little specific evidence to implicate disturbances of REM sleep in chronic insomnia. Although increased fast frequency EEG activity during NREM sleep has been demonstrated in several samples of insomnia subjects relative to controls, methodologies have varied widely among these studies. For instance, increased beta activity in one study was observed in subjects with “sleep state misperception” (paradoxical insomnia), but not psychophysiological insomnia, relative to controls.14 Another study showed increased beta in primary insomnia relative to insomnia with comorbid depression and controls.12 In addition to examining high-frequency EEG activity as an indicator of hyperarousal, some studies have also used quantitative EEG to measure delta EEG activity (0.5–4 Hz) as an indicator of homeostatic sleep drive in insomnia. These studies have also yielded variable results, with some showing reduced delta activity,11 but others showing no difference between insomnia and control samples,12,27 or a reduction only in “subjective” insomnia, but not “objective” insomnia.14 Although it may appear logical that EEG correlates of hyperarousal and homeostatic drive would inversely correlate in PI, previous published reports have presented only qualitative evidence to support this hypothesis.11,27 Most studies showing insomnia-control differences have focused on all-night NREM EEG activity, but others have focused on the sleep-onset interval.10,28 Some studies have also examined the time course of EEG power in different bands across successive NREM periods,11,27 generally finding stable differences across the night. However, other types of physiological data, such as plasma cortisol levels, suggest that individuals with PI may have particular evidence of hyperarousal in the first part of the night.8,9 Sex differences in quantitative EEG during sleep have also been identified in healthy individuals from adolescence to older adulthood,29–32 and among individuals with conditions such as major depressive disorder.33–35 However, sex differences have not been extensively examined in chronic insomnia. One study found higher relative beta EEG power in men than women among an older adult sample of insomnia and control subjects,14 but several other studies did not specifically examine sex differences. Likewise, the relationship between quantitative EEG characteristics and subjective sleep characteristics has received little attention. If high-frequency EEG activity were indeed a correlate of hyperarousal, one might expect that this variable would correlate with insomnia severity or sleep self-reports. Krystal and colleagues14 found that delta and beta power differed between subjective insomnia subjects and controls regardless of the degree of subjective underestimation of sleep, but that subjective ratings of sleep quality, restedness, and sleep efficiency were related only to delta power, and only among subjective insomnia subjects. Perlis and colleagues12 found that subjective underestimation of sleep time was related to higher beta activity in a sample that included PI, GSC, and depressed subjects. Thus, whether quantitative EEG characteristics are related to overall insomnia severity or to specific features remains an unresolved issue. In summary, previous findings regarding quantitative EEG characteristics of insomnia have provided inconsistent results, particularly regarding differences across NREM periods, sex effects, and clinical correlations. Therefore, the goals of the present analysis were: (1) to compare EEG power across successive NREM periods in well-characterized samples of primary insomnia (PI) and good sleeper controls (GSC); (2) to compare these findings for men and women separately; and (3) to examine relationships between quantitative EEG characteristics, baseline characteristics of insomnia, and self-reports of sleep.