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 CPI-613 clinical trial epinephrine, norepinephrine, and leptin (Sheer

et al. 2009). Technological Inhibitors,research,lifescience,medical 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 Inhibitors,research,lifescience,medical 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 Inhibitors,research,lifescience,medical 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 Inhibitors,research,lifescience,medical not only a secondary phenomenon but possibly also a causal factor. Inhibitors,research,lifescience,medical 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 TCL 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.