Insomnia is the most prevalent sleep disorder and is associated with significant psychosocial and somatic pathology. Up to 50% of the U.S. adult population reports symptoms of insomnia on a weekly basis and approximately 12% meets criteria for insomnia disorder (Ohayon 2002
). Cross-sectional studies demonstrate that 40–60% of individuals with insomnia exhibit depressive symptoms (Foley et al. 1995
; Ohayon et al. 1998
), 10–25% may have clinical depression, and 20–30% have anxiety disorder (Ohayon and Roth 2003
; Taylor et al. 2005
). Chronic insomnia is associated with reduced quality of life, higher absenteeism, impaired job performance, and higher healthcare utilization (Kuppermann et al. 1995
; Simon and VonKorff 1997
). In a large population-based study, a linear relationship was demonstrated between insomnia prevalence and number of self-reported comorbid medical disorders (Budhiraja et al. 2011
). Insomnia severity has been correlated with suicidal thinking in a clinical trial population (McCall et al. 2010
Although these cross-sectional associations are often interpreted to suggest that a variety of pathologies can result in secondary insomnia, prospective studies have found insomnia to be a risk factor for acute myocardial infarction (Laugsand et al. 2011
) and depression (Jaussent et al. 2011
). In long-term follow-up of 1741 individuals who had undergone polysomnography, insomnia was found to confer an independent and significantly increased risk for mortality (Vgontzas et al. 2010
). The question of how or why insomnia should be a risk factor for other pathologies likely overlaps with the question of what processes are responsible for the pathogenesis of insomnia itself. To answer one or both of these questions, conceptualizations and data from several lines of inquiry may be helpful.
The “hyperarousal” theory (Perlis et al. 1997
) highlights interplay between psychological and physiological factors in the etiology and perpetuation of chronic insomnia, including increased autonomic activity (Monroe 1967
; Adam et al. 1986
); activation of neuroendocrine and neuroimmunological axes (Vgontzas et al. 2001
; Burgos et al. 2006
), and altered brain metabolism, especially during the night (Nofzinger et al. 2004
). For instance, compared with normal controls, insomnia patients show significantly increased ratio of low- to high-frequency spectral power (LF/HF, sympathetic activation) of heart rate variability (Bonnet and Arand 1998
), increased production of cortisol (activity of the hypothalamic–pituitary–adrenal axis) and interleukin-6 (IL-6, activation of neuroimmunological axes) (Riemann et al. 2009
), and increased power in higher frequencies as measured by spectral analysis of the sleep electroencephalogram (EEG) at sleep onset (Perlis et al. 2001a
) and during nonrapid eye movement (REM) sleep (Perlis et al. 2001b
). Greater amplitudes, as measured by event-related EEG potentials, were observed in several latency ranges prior to, during, and on awakening (Devoto et al. 2005
; Steiger 2007
; Yang and Lo 2007
; Bastien et al. 2008
). Taken together, these data suggest that heightened cortical arousal may be either part of the pathogenesis of chronic primary insomnia or a consequence of it, or both.
Disruption of biological rhythms is another way to model the etiology and sequelae of insomnia (Reid and Zee 2009
). Virtually all physiological systems function on a rhythmic basis, and timing of their cycles is entrained through the influences of ambient light, physical activity, and feeding. Forced desynchronization of these systems by prolongation of a normal “day” from 24 to 28 h has been shown to cause reversal of the usual pattern of diurnal cortisol release, increases of insulin and postprandial blood glucose, and alterations in levels of epinephrine, norepinephrine, and leptin (Sheer et al. 2009
). Technological advances with cultural and economic shifts encouraging round-the-clock stimulation may exacerbate or cause insomnia in susceptible individuals through desynchronization of physiological mechanisms from their otherwise endogenous rhythms. Individuals with shift-work sleep disorder, for example, have been found to have electrophysiological evidence of reduced sensory memory and hyperattention to novel sounds, compared with healthy day workers (Gumenyuk et al. 2010
In convergence with the hyperarousal theory, it is well established that sleep disturbances including insomnia are common sequelae of traumatic stress (Spoormaker and Montgomery 2008
; Charuvastra and Cloitre 2009
; Pigeon et al. 2011
). A review of polysomnographic studies found that individuals with post-traumatic stress disorder (PTSD) have reduced slow wave sleep (Kobayashi et al. 2007
). Furthermore, it appears that pretraumatic sleep disturbance is a predictor for development of psychiatric morbidity after a traumatic event (Bryant et al. 2010
). Thus, with respect to traumatic pathology as well, it appears that sleep disturbance may be not only a secondary phenomenon but possibly also a causal factor.
Fundamentally, the nature of what sleep itself “is,” has not been established with definitive consensus. A long tradition of investigation has conceptualized sleep as a global state under top–down, central regulatory control (e.g., Saper et al. 2005
). This model describes competing homeostatic drives for sleep versus wakefulness and focuses on biochemical mediators of sleep including “sleep regulatory substances.” In contrast, a view of sleep focusing on synchronization of activity in local neural networks has been recently proposed (Krueger et al. 2008
). In this model, local assemblies of neurons (individual cortical columns) synchronize with one another in an activity-dependent way (i.e., following a period of stimulation). Perhaps counterintuitively, some regions of the brain can be described as being in a “sleep-state” while other regions are “awake.” Global, whole-organism sleep is explained as an emergent property of the local networks.
Although the local network synchronization model does not exclude the role of metabolic factors (and pharmacological interventions) as primary initiators of local sleep states, it would appear that the model has potential to re-frame the approach to therapeutics in sleep medicine, given the physics of oscillatory synchronization (as well as the relative ease of measuring phenomena related to neural synchronization, e.g., through EEG). Therapeutic strategies that target neural oscillatory aspects of sleep, through nonpharmacological mechanisms, may be particularly attractive, in consideration of the risk of side effects and dependency associated with many pharmacological interventions for sleep disorders.
High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM™, Brain State Technologies, LLC, Scottsdale, AZ) is a noninvasive approach to enhancing neurodynamic self-regulation by giving the brain an opportunity to perceive its own oscillatory pattern. HIRREM, also known as Brainwave Optimization™, uses sound (musical tones) to reflect the brain's changing pattern of frequency-specific electrical activity back to itself. In essence, the individual is given an opportunity to “listen” to his or her own brain. HIRREM musical tones are chosen on the basis of pattern-recognition algorithms in HIRREM software. Because of the identity between the dominant EEG frequency and the frequency of the musical tone, the phenomenon of resonance occurs between the individual's brain and the musical tones. The operational theory is that neural-musical resonance may be a mechanism for autocalibration of neural networks. Because the technology does not rely on entraining the brain toward operator-defined norms for the neural energetic ratios, HIRREM is considered a procedure for autocalibration of neural oscillations. Provision of the technology does not depend on clients' active cognitive engagement.
Use of HIRREM has been anecdotally associated with amelioration of a variety of symptoms including sleep complaints (L. Gerdes, pers. comm.), and so the aim of this pilot clinical trial was to evaluate the efficacy of HIRREM for relieving symptoms of insomnia. Our primary hypothesis was that the addition of HIRREM to usual care would be superior to usual care alone, for reduction of self-reported insomnia severity.