Sleep EEG Predictors and Correlates of the Response to Cognitive Behavioral Therapy for Insomnia

PRIMARY INSOMNIA (PI) IS A COMMON CONDITION THAT HAS A SIGNIFICANT IMPACT ON PUBLIC HEALTH.1–3 BOTH PSYCHOLOGICAL/BEHAVIORAL AND medication treatments have proven to be effective for the treatment of PI in many instances but are all associated with significant limitations.4–9 As a result, there is a need to develop improved treatments for this condition. One factor limiting this effort is that there is limited understanding of the pathophysiology of PI and of the neurophysiologic changes associated with the treatment response. Improved understanding of the pathophysiology of PI and physiologic correlates of the response to treatments would be helpful to develop new therapies that are specifically targeted to the physiologic aberrations that underlie PI symptoms.4 Toward this end, we sought to study the neurophysiologic effects of cognitive behavioral insomnia therapy (CBT), a psychological and behavioral treatment with well-established efficacy.7–9 Only very limited data exist concerning CBT's effects on neurophysiology. One prior study examined the effects of a similar behavioral treatment on the frequency spectrum of the electroencephalogram (EEG) in the presleep period among 12 individuals with sleep-onset insomnia.10 This study showed that individuals with sleep-onset insomnia had greater 13- to 31-Hz relative spectral power (power in the 13- to 31-Hz band divided by the sum of power in all frequency bands) prior to sleep onset than did healthy subjects without subjective reports of sleep-onset difficulty. Following behavioral therapy, those with insomnia showed a decrease in 13- to 31-Hz relative power in their presleep EEG. Another open-label study evaluated the effects of CBT on non-rapid eye movement (NREM) EEG spectral indices in 9 psychophysiological insomnia patients.11 That study showed that CBT increased the power of delta (0.5-4.75 Hz) activity, reduced the power of sigma (12-16 Hz) and beta (16-30 Hz) and led to a more rapid decline in delta power over the night. Based on these findings, the authors hypothesized that CBT may increase the homeostatic pressure for sleep. In the current investigation we sought to further evaluate the neurophysiologic effects of CBT. This study builds on the studies discussed above, as well as our prior research comparing all night averaged NREM EEG spectral indices derived from PI patients with sleep maintenance difficulties and from healthy individuals without evidence of sleep difficulty based on subjective measures.4 In our previous study, we found that patients with PI who underestimated their polysomnography-measured sleep time by at least 10% had decreased NREM EEG delta (0.5-3.5 Hz) and elevated alpha-(8.5-12 Hz), sigma-(12.5-16 Hz), and beta-(16.5-30 Hz) power, compared with both noncomplaining control subjects and PI sufferers who more accurately estimated their sleep times. This finding was consistent with the results of a previous study that found an association between increased high-frequency beta and gamma (> 30-Hz) NREM EEG spectral power and underestimation of polysomnography-measured total sleep time (TST) in a PI sample.12 We also found that traditional polysomnographic indices (e.g., sleep-onset latency [SOL], TST, wake time after sleep onset [WASO], number of awakenings, and duration and percentage of sleep in each of the sleep stages) were correlated with subjective sleep measures only among a subset of PI patients who did not underestimate their sleep time. In contrast, the subjective sleep measures of those who underestimated sleep time by at least 10% were correlated with NREM EEG spectral indices and not with traditional polysomnography measures. These findings suggest that, in some individuals with PI, alterations in NREM EEG frequency content are associated with a perception of wakefulness and/or a sense of impaired sleep that goes undetected by the traditionally-scored polysomnogram. For other patients with PI, traditional polysomnographic indices more strongly reflect subjective measures of sleep. The study reported herein employed the same NREM EEG spectral indices as our prior study but, in addition, examined measures of the time course of sleep EEG delta (0.5-3.5 Hz) power over the night based on the study of Cervena and coworkers on the EEG effects of CBT described above.11 We did not analyze data from the presleep or perisleep onset periods because of the extreme variability of the EEG in drowsiness, the presence of slow-eye movements during drowsiness, and the absence of artifact-free, waking, eyes-closed, nondrowsy data in a large number of subjects.4,13 Furthermore, in our prior study, we did not find evidence that the EEG frequency content in those with PI differed from normal sleepers in stage 1 sleep.4 In addition to the study of Cervena and colleagues, further rationale for the inclusion of indices of the time course of EEG delta power over the night comes from investigations suggesting that these indices are affected by behaviors such as spending excessive time in bed (TIB) and napping, practices that are common among patients with insomnia and are thought to perpetuate PI.14–18 Moreover, the amount of delta power in the early part of the night and the rate of decline in delta power are putative indices of homeostatic “sleep drive” that have been shown to be responsive to the types of manipulations of sleep-disruptive behaviors implemented with CBT. This therapy, in fact, is designed to increase the time awake throughout the day and, thereby, increase “sleep drive.”14–24 As a result, we hypothesized that changes in these delta power indices would correlate with improvement in CBT and, further, that lower initial NREM EEG delta power and a more gradual decline in delta power over NREM episodes might predict a successful response to CBT. Thus, we sought to test whether (1) some individuals have a relative deficit in initial “sleep drive”, as manifested in lower initial NREM EEG delta power and less rapid decline of delta power over time that is associated with their insomnia and (2) this deficit is addressed with CBT. This study also allowed us the opportunity to replicate our previous finding showing that traditional polysomnography indices and all-night averaged NREM EEG relative power indices are not correlates of subjective measures of sleep when studied across all individuals with PI. Instead, the relationship of these indices with subjective measures of sleep is dependent on the degree to which patients with PI underestimate their sleep time compared with polysomnography-derived TST.4 In the present investigation, we sought to test the hypothesis that the subjective improvement with CBT might follow a similar pattern. To test these hypotheses, we analyzed traditional polysomnography indices, all-night averaged NREM EEG relative power indices, and measures of the time course of sleep EEG delta power in individuals with PI before and after receiving a 6-week course of CBT (n = 16) or a placebo control therapy (PC) (n = 14).