You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
as depicted in figure 1a , the cortical activation necessary to maintain wakefulness is supported by an extensive network of subcortical structures and pathways .
major neurochemicals of this  ascending arousal system  include excitatory norepinephrine arising from the locus ceruleus ( lc ) , serotonin from the midline raphe nuclei , histamine from the tuberomammillary nucleus , dopamine from the ventral periacqueductal gray matter , acetylcholine from the pedunculopontine tegmentum , and the laterodorsal tegmentum of the pons and orexin from the perifornical area . despite their apparent redundancy , normal behavioral functioning may require all of these arousing systems .
for example , it is now clear that narcolepsy results from a selective loss of orexin - releasing neurons in the forebrain , accounting for the excessive daytime sleepiness , fragmented sleep , and cataplexy ( sudden muscle weakness without loss of consciousness ) associated with this disorder .
panel a depicts key elements of the ascending arousal systems , with diffuse excitatory projections to the cortex .
panel b shows pathways arising from the hypothalamus that inactivate the ascending arousal system during sleep .
ach , acetylcholine ; da , dopamine ; gaba , gamma amino - butyric acid ; gal , galanin ; ha , histamine ; ldt , laterodorsal tegmentum ; ne , norepinephrine ; orx , orexin ; pef , perifornical region ; ppt , pedunculopontine tegmentum ; tmn , tuberomammillary nucleus ; vpag , ventral periaqueductal gray matter ; 5-ht , 5-hydroxytryptamine . initiation and maintenance of sleep require suppression of activity in the ascending arousal systems .
this is accomplished by inhibitory neurons of the ventrolateral pre - optic area ( vlpo ; figure 1b ) , which remain active throughout sleep ( 3 ) .
the molecular  triggers  that activate the vlpo and initiate sleep onset have not been fully defined , but a substantial body of evidence points to extracellular adenosine as a candidate .
adenosine accumulates in basal forebrain during wakefulness and diminishes with ongoing sleep ( 4 ) .
adenosine receptors are expressed in the vlpo and adenosine activates vlpo neurons in vivo ( 5 ) , making it a reasonable candidate for the  sleep switch . 
caffeine and theophylline are potent adenosine receptor antagonists , which may form the basis for their well - known alerting effects . despite this evidence
, it is almost certain that other molecules also play important signaling roles controlling the initiation and maintenance of sleep . the monoaminergic arousal centers project to the vlpo and may serve to inhibit its activity ( 6 ) .
this creates the concept of  flip - flop  control of behavioral state , in which , at any given time , activity of either arousal - producing or sleep - producing neurons dominates and suppresses the other ( 3 ) .
in addition , the vlpo receives important circadian modulation from the suprachiasmatic nucleus  the central circadian clock ( 3 ) .
there exist two fundamentally distinct types of sleep : rapid eye movement ( rem ) sleep , which is associated with active dreaming , and non  rapid eye movement ( nrem ) sleep .
switches between nrem and rem sleep appear to be controlled by reciprocal inhibition between monoaminergic neurons and a specific subset of cholinergic neurons within the brainstem ( 7 ) .
these  rem - on  cholinergic neurons exhibit reciprocal inhibitory connections to noradrenergic ( lc ) and serotonergic ( raphe ) neurons ( 8) . when rem sleep is triggered , rem - on cholinergic neurons become maximally active , while noradrenergic and serotonergic neurons become virtually silent . the switching between activity and inhibition of these neurons results in a characteristic cycling between nrem and rem during the sleep period .
assessment of sleep / wake states can be made by behavioral observation , physiological monitoring , or a combination of the two .
behaviorally , sleep in adults is characterized by loss of consciousness and by relative immobility in a recumbent posture with the eyes closed . during nrem sleep , there is reduced tonus of large skeletal muscles that progresses to complete or near - complete atonia with a transition to rem sleep . throughout sleep , there is a relative sparing of activity among respiratory pump muscles .
visual , olfactory , auditory , somatosensory , and even nociceptive sensory responses all are diminished but not eliminated during sleep ( 9 ) .
physiologically , the gold standard for assessment of sleep and wake states is the laboratory polysomnogram ( psg ) . to conduct a psg ,
these sensors include multiple skin electrodes , which record brain activity ( electroencephalogram [ eeg ] ) , eye movements , submental muscle tone , leg movements , and electrocardiogram ( ecg ) .
thoracic and abdominal strain gauges , oral and nasal airflow sensors , and a finger probe to measure arterial oxygen saturation are also attached to the subject to help monitor respiration during sleep .
in addition to wakefulness and rem sleep , current clinical guidelines for scoring psgs identify three stages of progressively deepening nrem sleep : stages n1n3 ( 10 ) .
these stages are recognized and scored based on characteristic rhythms and events observed in the psg waveforms , but a detailed presentation of the scoring process is beyond the scope of this article ( 11 ) .
briefly , alert wakefulness is associated with a low - amplitude mixed frequency eeg pattern . as illustrated in figure 2 ,
drowsy wakefulness is associated with alpha waves seen as a rhythm with peaks in the 8- to 13-hz range .
drowsiness also is associated with slow rolling eye movements that may persist into light sleep .
the lightest stage of nrem sleep ( n1 ) is characterized by a loss of alpha rhythm and presence of theta waves with a characteristic frequency of 47 hz .
stage n2 sleep is marked by the expression of spindles ( burst - like trains of waves in the 11- to 16-hz range with a total duration 0.5 seconds ) and k - complexes ( well - defined biphasic waves lasting 0.5 seconds and usually maximal over the frontal cortex ) .
deep nrem sleep ( stage n3 ) is associated with large ( 75 v ) slow ( 0.53 hz ) waves known as delta waves .
typically , skeletal muscle activity exhibits progressively decreasing amplitude with transitions from wakefulness to n1 , n2 , and n3 sleep
. rem sleep is associated with the lowest skeletal muscle tone and with either sharp theta waves ( sawtooth waves ) or wake - like eeg patterns ( figure 2 ) .
eeg features of sleep / wake stages ( left ) and typical temporal organization of healthy nocturnal sleep in an adult ( right ) . for scoring purposes
, an overnight psg recording is divided into 30-second epochs , and a stage score is assigned to each epoch . visualizing this sequence of stage scores graphically as
a  hypnogram  highlights the temporal structure of the sleep process ( figure 2 ) . during a normal night
, the sleep process is cyclical , with sleep onset being followed by a rapid descent to deep stage n3 sleep within the first hour .
this is followed by cyclical alternations between nrem and rem sleep occurring every 6090 minutes throughout the rest of the night .
typically , most n3 sleep occurs during the first half - night , whereas most rem sleep occurs during the second half - night ( figure 2 ) .
the full biological and clinical relevance of this  ultradian  cycling of sleep depth remains to be determined .
psg data also are amenable to quantitative and continuous analysis using various signal processing techniques .
because the eeg rhythms associated with differing  levels  of alertness and nrem sleep can be differentiated according to characteristic frequencies , eeg power spectrum analysis has become a very popular sleep research tool ( 12 ) .
sleep and sleep quality also can be assessed subjectively , by self - report of the individual patient or research subject .
various mobile phone application  based , web - based , or paper sleep and activity logs have been developed and can be useful adjuncts to laboratory or home testing for both clinical and research purposes . although numerous standardized survey instruments have been developed to assess sleep quality , two have been very widely used : the pittsburgh sleep quality index ( 13 ) and the functional outcomes of sleep questionnaire ( 14 ) . in -
home psg testing has been performed without monitoring ( 15 ) , with remote monitoring ( 16 ) , and with in - home monitoring by a trained technician ( 17 ) .
the frequency of technically unacceptable recordings using these approaches ranges from about 10% to about 30% , and it is unclear whether any consistent cost savings accrue .
numerous other methods for home sleep testing have been developed that do not incorporate eeg monitoring .
the simplest of these is actigraphy , in which the subject wears a device  typically the size and shape of a wristwatch  on the nondominant wrist .
the device contains multiple accelerometers and can record movements continuously for periods of up to several weeks .
these movement profile data are then used to discriminate sleeping and waking periods , and their overall agreement with psg - based determinations is good , although results of individual validation studies have varied ( 18 ) .
this approach has been popular in research studies , allowing collection of many days of sleep / wake patterns in a natural environment .
some actigraphic devices also contain light intensity meters and event - logging buttons , allowing subjects to note when they go to bed and when they arise . for clinical applications , 
cardiorespiratory monitoring devices based on a wide array of technologies increasingly are being employed , but a thorough review is beyond the scope of this article .
typically , these devices monitor heart rate and its variability , respiratory effort and airflow , and arterial oxygen saturation .
these systems are commonly used to screen for clinically significant sleep apnea syndrome ( 19 ) .
plasma levels of most hormones exhibit significant 24-hour rhythms ( 20,21 ) , pointing to the importance of both the circadian clock and sleep - specific influences on their release and/or metabolism .
some hormones are little influenced by sleep versus wakefulness , including adrenocortotropic hormone , cortisol , and melatonin ; some are strongly influenced by sleep , such as thyroid - stimulating hormone ( tsh ) and prolactin ; and some are affected by particular sleep stages , such as growth hormone ( 20 ) . under normal conditions ,
studies using daytime naps or sudden changes in sleep schedule have shown that sleep onset , regardless of time of day , is associated with a stimulation of prolactin release ( 22 ) .
it has been suggested that a negative association exists between eeg delta activity and pulsatile prolactin release ( 20 ) .
growth hormone also exhibits a strong sleep - dependent rhythm , with secretion being specifically associated with stage n3 sleep ( 20 ) .
there is a strong association between the power of eeg delta activity and the rate of growth hormone secretion during sleep ( 23 ) .
furthermore , when ritanserin ( a serotonin receptor antagonist ) was used to augment deep sleep , the drug - related increase in eeg delta activity was associated with a proportional increase in the rate of growth hormone secretion ( 22 ) .
these findings strongly suggest that the mechanisms regulating delta wave production and growth hormone secretion are closely coupled , but these mechanisms have not been fully defined .
this is of potential relevance to the pathogenesis and management of diabetes , because the sleep - related increase in growth hormone secretion relates directly to reduced insulin sensitivity and increased plasma glucose levels during sleep ( 24 ) .
cortisol also exhibits a significant 24-hour pattern , but , unlike growth hormone , this appears to be primarily a result of circadian influences rather than of sleep per se ( 20 ) .
also in contrast to growth hormone , which peaks early during the sleep period , cortisol is at its nadir early during a nocturnal sleep period and peaks toward the end of sleep or in the early morning hours ( 24 ) .
there is some evidence that the sleep process does exert some inhibitory effect on cortisol release , and this may contribute to its nadir early in the sleep period .
this cortisol pattern also may contribute to increased glucose levels late in the sleep period , as cortisol may inhibit insulin release ( 24 ) .
tsh exhibits low daytime values , increasing during the evening and peaking around the time of sleep onset .
sleep , and especially stage n3 sleep , appears to exert an inhibitory influence on tsh secretion ( 20 ) .
n3 sleep is consistently associated with falling tsh levels , whereas awakenings are associated with rising tsh levels ( 25 ) .
this may be significant in diabetes pathogenesis , as tsh level has been negatively associated with various measures of insulin sensitivity .
however , cause - and - effect relationships remain to be determined ( 26 ) .
in summary , sleep is an actively regulated process significantly modulated by homeostatic influences that accumulate during ongoing wakefulness and dissipate during sleep and by circadian effects entrained to the 24-hour day .
sleep has a typical underlying architecture characterized by a rhythmic alternation between nrem and rem stages , and the transitions among sleep / wake states are orchestrated by a well - defined subcortical network of brain structures .
sleep and wake states also are characterized by distinct hormonal patterns that exert potential significant influences on metabolism and glucose homeostasis .
in brief far from a simple absence of wakefulness , sleep is an active , regulated , and metabolically distinct state , essential for health and well - being . in this article , the authors review the fundamental anatomy and physiology of sleep and its regulation , with an eye toward interactions between sleep and metabolism .