Contents



Preface

Changes in daily living circumstances over several decades have significantly affected sleep quality, propelling two revolutions in health care: a treatment revolution, which has been directed to the care of sleep disturbances, chiefly through pharmacological methods, and a research revolution, which has produced a novel understanding of the role of sleep in cognition. High-paced social and employment practices, for instance, have notably combined to make insomnia a major dysfunction affecting both physical and mental health, with nearly 30%–40% of the adult population

The need to treat insomnia and other sleep disorders has been the stimulus for developing pharmacologic interventions that, historically, have pursued an empiric approach. This approach has yielded drug candidates capable of alleviating sleep disturbances, but often with accompanying undesirable effects. Benzodiazepines, the first group of sleep medications developed, exhibited significant adverse effects like cognitive and psychomotor impairment, anterograde amnesia, nextday hangover, and rebound insomnia. Because of these adverse effects, the use of benzodiazepines for treatment of insomnia became controversial. In their place the non-benzodiazepine drugs like zolpidem, zaleplon, and zopiclone that followed all had high affinity and selectivity for the a1-subunit of the GABAA receptor complex, which improved sleep maintenance shortly after administration but lost this effect, however, at later sleep stages. These drugs too had adverse effects, which included daytime drowsiness, dizziness, headache, and nausea. In like manner, empirical approaches have yielded other drug candidates such as the orexin blockers with their own suite of advantages and disadvantages. Following this empirical progression has thus altogether yielded an extensive, proliferating, and somewhat bewildering variety of sleep medications, with the current pharmacopeia now exhibiting a broad

Coincident with the revolution in sleep pharmacotherapy there has been a parallel revolution in the understanding of the nature of sleep. While motivated chiefly by the health needs of increasing numbers of individuals suffering sleep disturbances, the study of the physical reality of sleep also presented itself as a strikingly interesting, universal feature of cognition. All known mammalian species notably exhibit sleep. This universal physical feature led to numerous studies that attempted to explain sleep's biophysical basis. Dominating the hypothetical landscape was the fact that sleep's defining feature entailed a sensory disconnection from afferent input. Addressing the why and how of this feature has now yielded key insights into the nature of sleep with a growing body of data coalescing around several models. These models point to a global influence in the modulation of the neuroplastic events of cognition and thus of an influence likely to be exerted on neurological functions

The text presented here is a recognition of these twin revolutions, which have been driven by the need to address a common and increasingly prevalent class of health

suffering from its mild to severe forms.

range of biological properties affecting sleep.

throughout the brain.

and social impairments.
