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Although MBSR produced a clinically significant change in sleep and psychological outcomes, CBT-I was associated with rapid and durable improvement and remains the best choice for the nonpharmacologic treatment of insomnia.

Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO2 < 10 mmHg) after the termination of seizures. This event lasted over an hour, is mediated by hypoperfusion, generalizes to people with epilepsy, and is attenuated by inhibiting cyclooxygenase-2 or L-type calcium channels. Using inhibitors of these targets we separated the seizure from the resulting severe hypoxia and show that structure specific postictal memory and behavioral impairments are the consequence of this severe hypoperfusion/hypoxic event. Thus, epilepsy is much more than a disease hallmarked by seizures, since the occurrence of postictal hypoperfusion/hypoxia results in a separate set of neurological consequences that are currently not being treated and are preventable.DOI: http://dx.doi.org/10.7554/eLife.19352.001

Circadian rhythms in several species can be phase-shifted by procedures that stimulate locomotor activity ("exercise") during the usual sleep period. The role of arousal or sleep loss, independent of activity, in this effect has not been adequately resolved. We show here, using the sleep deprivation procedure of gentle handling, that comparably large phase shifts (up to 240 min advances) of the rest-activity cycle can be induced in Syrian hamsters by 3 hr of behavioral arousal, with minimal locomotion, beginning 6 hr before the usual active period. Horizontal distance traveled during the deprivation procedure averaged ϳ0.08 km, compared to 2.5 km typical in exercise studies. Hamsters requiring fewer interventions exhibited larger shifts, suggesting that the level or continuity of spontaneous arousal determines shift size. The circadian rhythm of light-induced c-fos expression in the suprachiasmatic nucleus (SCN) was used as a phase marker to further demonstrate that the clock is reset within 1 hr after a 3 hr deprivation. Sleep deprivation mimicked the effects of exercise on basal c-fos expression in two components of the circadian system, suppressing basal Fos immunoreactivity in the SCN, and increasing Fos in the intergeniculate leaflet. Sleep deprivation without exercise in hamsters can rapidly reset the circadian clock and alter gene expression within the circadian system.Key words: circadian rhythms; nonphotic entrainment; c-fos; wheel running; phase shifts; suprachiasmatic nucleus Forty years ago, it was first suggested that an animal's state of arousal or level of locomotor activity might affect properties of its circadian clock (Aschoff, 1960). Convincing evidence followed some 25 years later, when it was demonstrated that running in an activity wheel can alter the period (Yamada et al., 1986) or shift the phase (Reebs and Mrosovsky, 1989) of circadian rhythms in nocturnal rodents. Since then, it has been shown repeatedly, using a range of arousing stimuli applied during the usual rest phase of the circadian sleep-wake cycle, that substantial phase advance shifts (up to 4 hr) are induced if subjects run during or after the stimulus but usually not if running is absent or prevented (Hastings et al., 1998;. Both the magnitude and the direction of these shifts are gated by circadian phase, with maximal phase advance shifts evident when activity is stimulated near the middle of the rest period and small phase delays (Յ1 hr) when activity is stimulated during the latter half of the usual wake phase of the circadian cycle (Bobrzynska and Mrosovsky, 1998).Although these studies implicate high intensity locomotor activity (i.e., exercise) as the behavioral stimulus critical for phase resetting in response to at least some arousing stimuli, the contribution that sleep loss or nonspecific arousal makes to the phase shifting process, independent of locomotion, has not been adequately resolved. Animals that run little after an arousing stimulus may fail to shift because they do not stay awake, whereas the occasional...

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The suprachiasmatic nuclei (SCN) control circadian oscillations of physiology and behavior. Measurements of electrical activity and of gene expression indicate that these heterogeneous structures are composed of both rhythmic and nonrhythmic cells. A fundamental question with regard to the organization of the circadian system is how the SCN achieve a coherent output while their constituent independent cellular oscillators express a wide range of periods. Previously, the consensus output of individual oscillators had been attributed to coupling among cells. The authors propose a model that incorporates nonrhythmic "gate" cells and rhythmic oscillator cells with a wide range of periods, that neither requires nor excludes a role for interoscillator coupling. The gate provides daily input to oscillator cells and is in turn regulated (directly or indirectly) by the oscillator cells. In the authors' model, individual oscillators with initial random phases are able to self-assemble so as to maintain cohesive rhythmic output. In this view, SCN circuits are important for self-sustained oscillation, and their network properties distinguish these nuclei from other tissues that rhythmically express clock genes. The model explains how individual SCN cells oscillate independently and yet work together to produce a coherent rhythm.

In mammals, the suprachiasmatic nuclei (SCN) of the hypothalamus control endogenous circadian rhythms and entrainment to the environment. A core SCN region of calbindin (CalB)-containing cells is retinorecipient and the cells therein lack rhythmic expression of clock genes and electrical activity. The core is surrounded by a 'shell' of rhythmic oscillator cells. In the present experiments, we studied the spatial arrangement of oscillator cells by examining the spatial and temporal patterns of expression of the canonical clock genes Per1, Per2 and vasopressin mRNA, a clock-controlled gene. Surprisingly, in the SCN shell, the dorsomedial cells were the first to rhythmically express both Per1 and VP mRNA, with gene expression then spreading very slowly through much of the nucleus for the next 12 h then receding to baseline levels. Following a light pulse, Per expression increased after 1 h in the core SCN and after 1.5 h in the shell. Although expression in the shell occurred earlier in light-pulsed animals than in those housed in constant darkness, it still followed the same spatial and temporal expression pattern as was observed in constant darkness. The results suggest that not only is the SCN organized into light-responsive and rhythmic regions but also that the rhythmic region of the SCN itself has an ordered arrangement of SCN oscillator cells.