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Clin Neurophysiol. 2006 September ; 117(9): 1885–1901. doi:10.1016/j.clinph.2006.01.017.
Vigilance, alertness, or sustained attention: physiological basis

and measurement
B.S. Okena,b,*, M.C. Salinskya, and S.M. Elsasa

aDepartment of Neurology, Oregon Health & Science University (OHSU), CR120, 3181 SW Sam
Jackson Park Road, Portland, OR 97239, USA

bDepartment
of Behavioral Neuroscience, CR120, Oregon Health & Science University (OHSU),
3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
Abstract
Vigilance is a term with varied definitions but the most common usage is sustained attention or tonic
alertness. This usage of vigilance implies both the degree of arousal on the sleep–wake axis and the
level of cognitive performance. There are many interacting neural and neurotransmitter systems that
affect vigilance. Most studies of vigilance have relied on states where the sleep–wake state is altered,
e.g. drowsiness, sleep-deprivation, and CNS-active drugs, but there are factors ranging from
psychophysics to motivation that may impact vigilance. While EEG is the most commonly studied
physiologic measure of vigilance, various measures of eye movement and of autonomic nervous
system activity have also been used. This review paper discusses the underlying neural basis of
vigilance and its assessment using physiologic tools. Since, assessment of vigilance requires
assessment of cognitive function this aspect is also discussed.
Keywords
Arousal; Attention; Sleep deprivation; EEG; Evoked potentials; Cognition; Vigilance
1. Introduction
There are activation states of cerebral cortex that impact the ability to process information
where the activation itself contains no specific information. These activation states can be tonic
or phasic and may be relatively global or more localized. Terms that have been used to describe
these states include arousal, alertness, vigilance, and attention. Unfortunately, no terms are
ideal to describe these states of cortical activation since most terms are in broad use with varied
associations and there are not perfect physiological markers. The term vigilance, in particular,
has unfortunately been used in different ways by different groups of scientists. Psychologists
and cognitive neuroscientists use the term to describe an ability to sustain attention to a task
for a period of time (Davies and Parasuraman, 1982; Parasuraman, 1998). They often
specifically refer to a vigilance decrement, the decline in attention-requiring performance over
an extended period of time (Mackworth, 1964). Animal behavior scientists and psychiatric
clinicians use the term vigilance similarly but more specifically referring to attention to
potential threats or dangers, with hypervigilance being one of the symptoms of post-traumatic
stress disorder (American Psychiatric Association, 1994). This usage of vigilance is probably
closest to the common lay usage and to the English dictionary primary definitions of vigilance,
© 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
*Corresponding author. Tel.: + 1 503 494 8873; fax: + 1 503 494 9520. oken@ohsu.edu (B.S. Oken).
Oken et al. Page 2
e.g. ‘state of being alertly watchful, especially to avoid danger’ (Merriam-Webster [online],
2005). A third group of scientists are clinical neurophysiologists who sometimes use the term
vigilance level to refer more narrowly to arousal level on the sleep–wake spectrum without
any mention of cognition or behavioral responsiveness. This is partly related to the EEG’s
exquisite sensitivity to the activity of the corticothalamic networks underlying the sleep–wake
dimension (Steriade, 1999). It also may relate to the lack of lay usage of the term vigilance in
languages other than English, the translation of the English word arousal into a more medically
used term vigilance in French and Vigilanz in German, and to a less common English definition
of the term vigilance. Most would consider arousal or wakefulness an aspect of vigilance
(Parasuraman et al., 1998) and in many cases the two are very closely related, e.g. with sleep-
deprivation. For this discussion, vigilance will mean sustained attention, the most common
scientific usage.
Arousal is another term that is used differently by different groups of scientists but more
consistently refers to non-specific activation of cerebral cortex in relation to sleep–wake states.
While vigilance as we have defined it is conceptually distinct from arousal, most research on
vigilance has, in fact, studied alterations in arousal through the use of subjects who are sleep-
deprived, have sleep disorders, or are taking sedative medications. This problem is
compounded by the fact that relative sleep-deprivation is common in the overtly healthy
population (Bonnet and Arand, 1995b; Levine et al., 1988) contributing to healthy subjects
becoming drowsy during performance of a prolonged, often tedious task. Thus, the aspect of
vigilance distinct from arousal that requires a normally awake person to attend to a task for a
prolonged period has not been as well-studied physiologicially. Attention usually refers to a
more focused activation of cerebral cortex that enhances information processing (Mesulam,
1990; Mountcastle, 1978; Parasuraman, 1998; Posner and Petersen, 1990) but one aspect,
sustained attention, is used synonymously with the most common usage of vigilance
(Parasuraman, 1998b). While focused attention, divided attention, and shifting of attention, as
well as executive control of attention, are all important, sustained attention is the aspect closely
related to the alertness systems and the only attentional aspect that will be discussed in detail.
Alertness is another term that overlaps with arousal but more specifically includes some
cognitive processing. Some researchers use the terms phasic and tonic alertness (Nebes and
Brady, 1993; Posner and Petersen, 1990). Phasic alertness relates to the orienting response
(Sokolov, 1963) and tonic alertness will be used synonymously to vigilance and sustained
attention.
This review paper of the biologic bases and physiologic correlates of vigilance, perhaps better
referred to as tonic alertness or sustained attention, encompasses an extremely large field. The
paper focuses on the basic underlying mechanisms including animal studies and on physiologic
measurements that have been related to these states, including EEG, event-related potentials,
eye movements, and measures of autonomic nervous system activity. The human
electrophysiology section focuses on just several conditions associated with altered alertness:
the normal wake–sleep transition, sleep-deprivation and sleep fragmentation, as well as
declines on sustained continuous performance tasks. Some relevant topics such as drug effects
were omitted in the interest of space. Additionally, only a subset of excellent papers could be
cited.
2. Underlying mechanisms and physiology

Alertness and sustained attention to the environment have multiple underlying brain processes
and related psychological constructs. A very important aspect already referred to is the sleep–
wake state, dependent on multiple brain-stem–thalamo–cortical pathways. There are also many
modulatory systems that impact the sleep–wake state and alertness. These neural-based
systems include the suprachiasmatic nucleus–circadian rhythm (Dijk and Czeisler, 1995), the

Oken et al. Page 3
hypothalamo–pituitary–adrenal axis, and limbic system (including amygdala and nucleus

accumbens). Also, alertness may be modulated by metabolic systems and substrates such as
thyroid, glucose, oxygen and electrolytes. Additionally, to sustain attention there needs to be
motivation and cognitive processing.
2.1. Sleep–wake systems

The sleep–wake aspect is probably the most studied component of alertness and sustained
attention in terms of underlying mechanisms and physiological correlates and thus is the focus
of much of this discussion. The multiple brain structures and neurotransmitter systems
responsible for the sleep–wake state are highly interconnected and usually interact in
predictable ways, but may become dissociated in pathologic states. Even during the awake
state a person may be more or less engaged in processing or responding to environmental
stimuli. In catatonia there is intact wakefulness but a significantly reduced ability to interact
with the environment. Cataplexy is associated with conscious wakefulness but atonia related
to partial intrusions of REM sleep. Fatal familial insomnia (FFI) associated with thalamic
pathology produces marked decreases in total sleep and REM time with the awake state
characterized by increased slowing, decreased alpha and deficits in attention and vigilance
(Lugaresi, 1992; Sforza et al., 1995). In persistent vegetative state, severe dementia, or
minimally conscious states, there may be some preservation of sleep–wake cycles. However,
even though awake in some sense, i.e. EEG state change with eyes open, the alertness or
cognition of the person in a persistent vegetative state is essentially absent.
The brain systems underlying the sleep–wake state include both wakefulness-promoting and
sleep-promoting components which are interconnected and mutually inhibitory. The relevant
systems include: the hypothalamus (tuberomamillary histaminergic projections and preoptic
nuclei); the serotonin projection system from the raphe nuclei; the norepinephrine projection
system from the locus coeruleus; the cholinergic system including both thalamic projections
from the midbrain and cortical projections from basal forebrain regions; and several thalamic
nuclei. While a detailed understanding of the brain systems contributing sleep is well beyond
the scope of this paper, the systems are important for normal alertness and sustained attention
and are affected by pathologic states and medications altering alertness and sustained attention.
The first observation of a wake-related structure was that intact brain-stem structures above
the midpons were critical to maintaining arousal as evidenced by EEG recording in cats
(Moruzzi and Magoun, 1949). Originally termed the ascending reticular activating system,
critical constituents of this are thalamic projections from the upper brain-stem: the cholinergic
pedunculopontine and laterodorsal tegmental nuclei. Other components are the monoaminergic
systems projecting from the brain-stem. In addition, there are two wakefulness promoting
systems in the hypothalamus: the histamine projections from the tuberomammillary nucleus
and the hypocretin (orexin) projection system. The hypocretin neurons have widespread
projections to major nuclei related to sleep–wake state in brain-stem and thalamus and are
associated with neuroexcitatory activity (de Lecea et al., 1998). The declines in alertness and
increased sleep propensity that occur in narcolepsy are associated with hypocretin deficiency
(Mignot et al., 2002; Nishino et al., 2000).
In addition to systems to promote wakefulness there is at least one hypnogenic or sleep-

promoting system. Following the description by von Economo of persistent insomnia following
hypothalamic lesions (von Economo, 1930) it has become established that the preoptic area of
the hypothalamus is critical in inducing sleep, with lesions of the ventrolateral preoptic nucleus
region producing as much as a 50% sustained decrease in sleep (Lu et al., 2000; McGinty and
Szymusiak, 2001; Saper et al., 2001). Failure to sleep also occurs with the thalamic lesions
seen with fatal familial insomnia (Lugaresi, 1992). This disorder produces significant
neuropsychological deficits often centering around attentional deficits (Gallassi et al., 1992).

Oken et al. Page 4
Two distinct thalamocortical activity states related to alertness and attention are associated
with specific states of thalamic projection neurons: burst and tonic. The burst state results from
relative hyperpolarization and the tonic state from relative depolarization of the resting
membrane potential (McCormick and Bal, 1997; Steriade et al., 1993). During EEG
synchronized sleep when the thalamic neurons are hyperpolarized and in burst mode, there is
a diminished responsiveness of thalamic sensory neurons to stimuli within their receptive fields
with lowered signal-to-noise ratio (Livingstone and Hubel, 1981; McCormick and Feeser,
1990). The thalamic burst and tonic activity states are seen in thalamocortical relay and
thalamic reticular nucleus neurons. Sleep transition is associated with hyperpolarization of
thalamo-cortical neurons and disinhibition of thalamic reticular neurons. These changes alter
transmission of signals conveying information from external environment and help generate
sleep spindles (Steriade, 1999). During slow wave sleep, the thalamocortical activity consists
of synchronous rhythmic activity (EEG delta waves and sleep spindles) associated with burst
states in thalamic projection neurons (McCarley et al., 1983). During the awake state there is
some sort of cortical activation, presumably related to partial neuronal depolarization bringing
neurons closer to firing levels (Steriade, 2000). The tonic state produced during the awake and
REM sleep states, produces less rhythmic, less synchronous, lower amplitude thalamocortical
activity (McCormick and Bal, 1997; Steriade, 2000).
2.2. Neurotransmitter systems

There are several neurotransmitter systems that are relatively non-specific in that they do not
carry specific motor or sensory information but they modulate thalamic and cortical activation
(Robbins, 1997). The locus coeruleus– norepinephrine, raphe–serotonin, and
tuberomamillary– histamine systems are active while awake, decrease during slow wave sleep
and are decreased further during REM sleep. The cholinergic system is active while awake,
less active in non-REM sleep and increases during REM sleep to a similar level as awake.
Thus, the monoaminergic differences between the awake and REM state suggests that the
norepinephrine and other monoaminergic systems are necessary to direct attention or weight
of cortical processing to external sensory stimuli. This is in contrast to REM sleep where there
is significant cortical activation and even awareness to some degree (of dreams) but little
processing of external sensory stimuli. Changes in these neurotransmitter systems are critical
to state changes as further evidenced by firing rate changes in cholinergic and norepinephrine
neurons preceding state transitions as assessed by EEG or behavior (Aston-Jones and Bloom,
1981a; Steriade et al., 1982). All the systems related to alertness, including the
neutortransmitter specific systems, are highly interconnected with direct projections between
many of the relevant nuclei. This presumably contributes to the redundancy and compensatory
responses such that fairly extensive bilateral lesions of LC are necessary in animals before
there is background EEG slowing (Berridge et al., 1993). Additional neurotransmitters
impacting alertness via the sleep–wake state but not discussed further include glutamate,
gamma aminobutyric acid, nitric oxide, endorphins, and adenosine (Pace-Schott and Hobson,
2002).
2.2.1. Locus coeruleus–norepinephrine—The Locus coeruleus–norepinephrine (LC–

NE) system highlights the tonic and phasic aspects of alertness and attention. The concept that
NE output is modulatory is consistent with LC neurons being activated synchronously and
non-specifically via electronic coupling. In addition to the tonic sleep–wake state dependent
LC changes, there is phasic activation of the LC during the awake state (Aston-Jones and
Bloom, 1981b; Berridge and Waterhouse, 2003). This phasic activation improves network wide
enhancement of sensory processing of salient environmental stimuli and is thought to occur
through improvement of signal to noise ratios in neurons or altering receptor field properties
such that there is a decreased threshold for response (Berridge and Waterhouse, 2003). The
P3-like event-related potentials in monkeys are attenuated by lesions of the LC (Pineda et al.,

Oken et al. Page 5
1989) even though the mean latency of the LC neuronal responses to the infrequent target
stimuli in this paradigm is 90 ms, which is much less than the latency of the P3-like potential.
The latency to LC response is correlated with behavioral performance such that LC responses
are longer during epochs with poor performance or lowered vigilance (Aston-Jones et al.,
1994).
2.2.2. Cholinergic systems—Brain-stem and basal forebrain cholinergic activity are

critical for sleep–wake state determination and the basal forebrain cholinergic projections to
cortex are important for modulation of cognitive function, with attention being an important
aspect (Everitt and Robbins, 1997; Szymusiak, 1995). There is some conflicting data on
whether there is a significant cholinergic effect on sustained attention (Dalley et al., 2004; Gill
et al., 2000; Grottick et al., 2003). The cholinergic system has a direct impact on EEG, with
cholinergic activity in cortex being related to wakefulness and desynchronization of the EEG
(Celesia and Jasper, 1966; Vanderwolf and Robinson, 1981). Nicotine increases some
measures of EEG alertness (Griesar et al., 2002) but its mechanism is not solely cholinergic
because nicotine acts presynaptically on neurons utilizing different neurotransmitters. Nicotine
has produced similar effects to hypocretin on sustained attention in rats (Lambe et al., 2005).
2.3. Other factors impacting sustained attention

In addition to the impact of overt sleep–wake systems, there are other brain systems that are
necessary for sustained attention to environmental stimuli. The attentional systems overlap in
part with some of the sleep–wake systems but there are differences. As already noted, the LC–
NE system is important for sleep–wake state changes but it is also phasically active for attention
to environmental stimuli while awake. To further consider the other brain systems, it is helpful
to recognize awake states where well-rested subjects may have low vigilance. Examples
include catatonia, apathy, and attention deficit disorder.
2.3.1. Motivation—One psychological construct with its underlying brain systems impacting
sustained attention is motivation. Based on animal as well as human lesion studies, the
motivational system includes portions of the frontal lobes (e.g. anterior cingulate) as well as
limbic and subcortical structures (striatum, nucleus accumbens, amygdala) and much of the
dopamine system (Robbins and Everitt, 1996). The dopamine system may be related to reward
but can also be thought of as relating to a stimulus’ predictive value of reward (Schultz,
2002). Subjects who are uninterested in the environment or apathetic will not be as vigilant as
those with high motivation. Performing a task with a high financial reward for performance
will engage the attentional system stronger and with longer duration than performing the same
task with no overt reward for performance. The P3 amplitude is increased with financial
incentives for performance (Begleiter et al., 1983; Hömberg et al., 1981). Conceptually, effort
(Kahneman, 1973) and motivation are related. The extensive literature on physiologic
correlates of mental effort generally does not encompass sustained attention. One physiologic
measure, frontal midline theta, has correlated with mental effort on working memory tasks and
may reflect activity of anterior cingulate cortex (Gevins et al., 1997; Ishii et al., 1999; Jensen
and Tesche, 2002; Onton et al., 1995). However, it is not clear if frontal midline theta represents
an activation or deactivation of anterior cingulate (Mizuhara et al., 2004).
2.3.2. Stress—Stress (or stressor) describes an event or condition that elicits a certain pattern
of physiologic and behavioral responses (McEwen, 2000), with chronic and acute stress
producing different responses. Stress has an impact on sustained attention task performance
(Hancock and Warm, 2003). The most studied physiologic responses to stress are activation
of the hypothalamic–pituitary–adrenal (HPA) axis and the LC–NE-sympathetic nervous
system pathway. The amygdala and parasympathetic system also interact with this latter
pathway (Bernston et al., 1991). The function of the amygdala impacts vigilance and is thought

Oken et al. Page 6
to be affected by post-traumatic stress disorder which is associated with hypervigilance,

difficulty concentrating, and sensitization of the startle response (Davis and Whalen, 2001).
Some of the interaction between stress and alertness is presumably mediated via the amygdala
and its corticotrophin-releasing factor inputs to the LC (Valentino et al., 1992). A mild
physiologic stress such as exercise may delay EEG measured sleep onset (Bonnet and Arand,
1998). Markers for stress and autonomic nervous system activity have included EEG (various
measures of percent alpha or slow wave frequencies), skin temperature, electrodermal activity,
heart rate and heart rate variability, breathing (rate, depth, pCO2 and pO2), and blood pressure.
Certain levels of stress may improve cognitive function, suggesting a U-shaped curve
relationship (see Section 2.4).
2.3.3. Cognitive aspects and habituation—Vigilance is affected by some cognitive

aspects of the stimuli in addition to the overt rewarding or motivational values. For example,
psychophysical variables of external stimuli that affect vigilance include signal modality,
intensity, duration, background, event rate, signal probability, and regularity (Parasuraman,
1998b). Executive attention as measured by working memory load or cognitive control are
other psychological parameters critical to the vigilance decrement (Caggiano and Parasuraman,
2004; Fisk and Schneider, 1981; Parasuraman, 1979). Decision-making response criteria may
also be impacted by vigilance tasks (Loeb and Alluisi, 1984; Parasuraman, 1979).
The brain has a network of changes in response to novel stimuli (Ranganath and Rainer,
2003). Novel stimuli elicit an orienting response as well as the novelty P3 or P3a (Oken,
1997; Squires et al., 1975). Novel stimuli may automatically engage the attentional system and
thereby produce improvements in sustained attention compared with more repetitive tasks.
Repeated presentations of the same stimuli often produce decreased responses especially of
the orienting response (Rockstroh et al., 1987). Many physiological measures including skin
conductance, event-related EEG desynchronization, and P3 show some degree of habituation
and the speed of habituation may relate to the vigilance decrement (Siddle, 1972). Most studies
of vigilance use tasks that involve significant repetition where there will be habituation to the
stimulus and decreased orienting.
One can presumably have intact sustained attention without an overt motor response but given
the usual experimental designs, the relationship of vigilance to motor systems may also be
important. Physiological measurements of motor fatigue have been evaluated, mostly using
some EMG measures with repetitive activity (Lou et al., 2003; Vollestad, 1997). However,
these have not been specifically evaluated in relationship to sustained attention. Mental fatigue
is presumably identical or very closely related to sustained attention and vigilance as defined
in this paper.
2.4. Physiologic correlates

Often there is a U-shaped curve relating performance to these various factors impacting cortical
activation, such that performance is maximal at arousal states that are neither very low nor very
high. This was first described almost 100 years ago with the use of mice that best learned a
task with intermediate levels of electric shock; mice receiving negligible or very high level
electric shock did not learn as well (Yerkes and Dodson, 1908). This U-shaped curve continues
to be relevant for many aspects of alertness and attention. In general, the phasic alerting and
attentional systems may be most critical when stimuli are near threshold (Reynolds et al.,
2000).
There are many physiologic signals that have been utilized to assess alertness and sustained
attention, only some of which are mentioned in this section. Overall there is increased slow
frequency activity on the EEG and decreased amplitude of event-related potentials with
decreasing vigilance. Additionally, during maximal attention, some awake frequencies, e.g.

Oken et al. Page 7
alpha, are attenuated. This was initially described as event-related desynchronization

(Pfurtscheller and Aranibar, 1977). However, event-related attenuation may be a better term
because synchrony was often not directly measured and it has become clearer that the
maximally alert state is associated with synchronous activity recorded from cortex, just at faster
frequencies, e.g. gamma frequencies (Kaiser and Lutzenberger, 2004; Steriade et al., 1996).
These gamma frequencies are difficult to reliably discern in scalp EEG because the skull acts
as a low pass filter and EMG artifact contains much activity in the gamma frequencies.
There are several EEG measures used to relate activity in two locations. Neuronal synchrony
is a recently developed technique derived from the decomposition of the oscillatory EEG
signals in a defined frequency band into amplitude and phase (Lachaux et al., 1999). Large-
scale neuronal synchrony has been proposed as a functional link between separate brain regions
(Varela et al., 2001). The observation that event-related potentials may dynamically arise from
partial phase resetting rather than from amplitude responses in an otherwise silent system
(Makeig et al., 2002, 2004) underscores the functional significance of neuronal phase
synchrony. This method of obtaining EEG synchrony information differs from the related
measure, coherence. While coherence is calculated using fast Fourier transformation,
synchrony is usually calculated using wavelet transformations (Le Van Quyen et al., 2001). A
significant advantage of synchrony over coherence for the study of attentional phenomena is
that by using wavelet analysis, synchrony can be calculated with higher temporal resolution
than FFT methods that require several seconds or more of EEG data to calculate coherence.
Using magneto-EEG to investigate the attentional blink phenomenon, neuronal synchrony in

the beta band locations was increased during successful detection (non-blink) and decreased
during missed letters (attentional blink) (Gross et al., 2004). Event-related covariance is another
measure of relationship between different locations and decreases in event-related covariance
have been related to performance decrements on sustained attention tasks (Gevins et al.,
1987).
3. Conditions associated with changes in alertness and sustained attention

To further understand the alertness and sustained attention systems, the physiology associated
with altered attentional conditions will next be discussed: the usual awake–sleep transition and
sleep deprivation. Due to space limitations of this review, declines in vigilance associated with
other conditions will not be discussed further, including attention-deficit hyperactivity disorder
(Barkley et al., 1992), sleep apnea (Engleman and Martin, 1994; Verstraeten and Cluydts,
2004) and narcolepsy (Valley and Broughton, 1983).
3.1. Drowsiness
3.1.1. Awake–sleep transition—When an awake, alert person gradually falls asleep there
is a transition from being fully awake to being clearly asleep. This transition is of great
importance to understanding clinically relevant changes in alertness and sustained attention
and is associated with well-established EEG changes (Dement and Kleitman, 1957; Matousek
and Petersen, 1983; Rechtschaffen and Kales, 1968; Santamaria and Chiappa, 1987b). Some
EEG changes in stage 1 sleep relate to the alpha rhythm: anteriorization, slowing by 0.5–2.0
Hz, fluctuations in amplitude and, eventually, loss of alpha activity. There is increased slow
wave activity more often in the frontal and central regions, brief runs of anterior beta activity
and vertex waves. Stage 2 is more clearly defined because of the appearance of sleep spindles
and/or K complexes. The transition into stage 1 is particularly difficult to judge from the EEG
in subjects with little or no alpha activity. The transition from awake to stage 2 sleep often
involves many transitions between awake and stage 1 prior to stage 2 sleep onset. While the
more precise EEG criterion of stage 2 sleep is often used to define sleep onset, it is apparent
there is actually a sleep onset period beginning while awake and extending to at least stage 2
(Ogilvie, 2001). Some have tried to expand the staging of this sleep onset period by including

Oken et al. Page 8
up to 9 substages (2 awake, 6 stage 1, 1 stage 2 (Hori et al., 1994)). However the temporal
pattern of EEG changes is not uniform across all subjects (Santamaria and Chiappa, 1987b) so
this classification based on many patterns is often difficult to implement accurately. In addition
to conventional EEG changes, there is decreased amplitude of long-latency evoked potentials

(Haider et al., 1964) and of the contingent negative variation (Naitoh et al., 1971; Tecce,
1979).
There are also developmental changes in the EEG during the sleep onset period associated with
decreased alertness. The transition from normal waking to sleep in children is associated with
runs of high voltage slow waves, also called hypnagogic hypersynchrony (Eeg-Olofsson,
1971). In adolescents and young adults, there may still be rhythmic frontal 5–7 Hz activity
during this transition. At the other end of the age spectrum, frontal delta slowing may be seen
during drowsiness in elders, although if the amplitude is over 100 micv it may suggest
pathology.
3.1.2. Sleep–wake transition—The transition from sleep to awake is similar

physiologically to falling asleep although the EEG transition is usually more rapid.
Behaviorally, there is a period referred to as sleep inertia following awakening from sleep,
during which the EEG reveals awake state but there is decreased cognition and responsiveness
to stimuli compared to an awake period compared to what is observed after several more
minutes, or even hours, of wakefulness (Simon and Emmons, 1956; Webb and Agnew,
1964). The duration of this decreased performance following arousal on a sustained attention
task may last an hour or more (Ferrara et al., 2000; Jewett et al., 1999), but more typically
dissipates in 5–35 min (Akerstedt et al., 1989). In fact, sleep inertia is paradoxical because
people immediately arising from sleep (when they should be most refreshed) consistently
perform more poorly than they did hours earlier, just before going to bed (when they should
have been most fatigued). Sleep inertia is not dependent on circadian rhythm (Naitoh et al.,
1993) but is partly dependent on the stage of sleep from which one is awakened, e.g. full
awakening typically is quicker from stage 1 than slow wave sleep.
3.1.3. Quantitative EEG measures—Using more quantitative measures for alertness,

there is an increase in slow frequencies and decrease in fast activities during the sleep onset
period, with different investigators advocating using various measures or ratios of theta and
delta with beta and alpha (Gevins et al., 1977; Matousek and Petersen, 1983; Merica and
Gaillard, 1992). The theta changes are more prominent frontally while the alpha changes may
be more generalized (Strijkstra et al., 2003). There are differences between drowsiness with
the eyes open and closed, e.g. decreased alertness may be associated with increasing alpha
band activity with eyes open but decreasing alpha activity with eyes closed. While reliabilities
and sensitivities for the quantitative EEG parameters using visual EEG scoring as the gold
standard may approach 90%, the conventional visual scoring of drowsy onsets and offsets
varied by more than 5 s in 29% of episodes judged by three scorers (Gevins, 1977). One
limitation of the usual quantitative approach is the intersubject variability of key parameters
denoting decreased alertness. For example, subjects with low amplitude awake alpha activity
have different EEG changes of sleep onset than those with high amplitude alpha. Additionally,
conventional EEG frequency analysis does not take advantage of specific patterns, such as
vertex waves and sleep spindles. For example, sleep spindle frequencies may overlap with
awake alpha frequencies. There is a circadian contribution to the EEG changes during non-
REM sleep (Dijk and Czeisler, 1995). Quantitative techniques using within subject parameter
provide additional benefit (Penzel and Petzold, 1989).
3.1.3.1. EEG-performance relationship: There is a very large literature concerning the

relationship of EEG measures and performance on sustained attention tests including simulated
driving as well as more conventional psychological tests. The intersubject correlation between

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EEG and performance changes on a sustained attention task is not consistent or large, especially
in well-rested subjects (Belyavin and Wright, 1987; Boddy, 1971; Cajochen et al., 1999;
Kornfeld and Beatty, 1977; Otmani et al., 2005; Townsend and Johnson, 1979; Valentino et
al., 1993; Williams et al., 1962). The two measures that more often correlate with worse
performance are increasing theta and decreasing beta. Similar to the univariate EEG measures,
multivariate EEG changes do not correlate well with performance on a sustained attention task
until performance is markedly diminished, with decreased beta activity being the most useful
discriminant (Belyavin and Wright, 1987). This study also observed that the EEG correlated
greater with performance on a sustained attention task requiring working memory rather than
simply visual discrimination, reinforcing the observations regarding vigilance decrements and
working memory described in Section 2.3.3.
Intrasubject analyses have generally yielded better results with more consistent correlations
between performance and EEG changes, especially if subjects are drowsy (Makeig and Inlow,
1993; Torsvall and Akerstedt, 1987). While theta and alpha are more consistent markers related
to performance, one study reported decreased beta in the seconds prior to stimulus presentation
being a better marker than increased theta (Townsend and Johnson, 1979). Makeig and
colleagues, using a moving window with higher target presentation rates, observed a consistent
within subject correlation between increases in slow activity and decreases in fast activity with
performance on a vigilance task, often recording from just a central and a parieto-occipital
electrode (Fig. 1) (Jung et al., 1997; Makeig and Inlow, 1993; Makeig and Jung, 1995, 1996).
The EEG changes were somewhat different in tasks in which the eyes are open compared with
the eyes closed task, perhaps highlighting why alpha frequency activity may not be a very
reliable intersubject correlate of performance changes. The decreased performance and EEG
changes similar to drowsiness may cycle at lengths on the order of 15 s to many minutes (Conte
et al., 1995; Makeig and Inlow, 1993; Makeig and Jung, 1996). Not unsurprisingly, changes
in 14 Hz activity (presumably spindles) in the epochs preceding stimulus presentation were
associated with performance only when error rates were very high (Jung, 1997; Makeig and
Jung, 1996). Using the full EEG power spectrum to predict alertness as measured by reaction
time performance was slightly better than simply using EEG at 5 specific frequencies they had
previously shown to be sensitive to alertness changes (Jung, 1997).
3.1.3.2. Responsiveness: During the sleep onset period there is gradually decreased
responsiveness to environmental stimuli as assessed by either reaction time or the stimulus
intensity needed to elicit a response (Bonnet and Moore, 1982; Ogilvie and Wilkinson,
1984). More recently a standardized measure of behavioral responsiveness to light flashes, the
Oxford sleep resistance (OSleR) test, has been used (Bennett et al., 1997) and does correlate
strongly with the EEG-based maintenance of wakefulness test (see below) (Krieger et al.,
2004). On the OsleR test, sleep onset is considered to occur when a subject fails to press a
switch in response to 7 light emitting diode flashes that occur once every 3 s. Since many
control subjects have no loss of responsiveness on the time-limited OSleR (Mazza et al.,
2005), the lack of behavioral response in a clinical population is considered a marker for sleep
onset, rather than simply inattention. Of note, however, there is a significant intersubject
difference in terms of relationship of behavioral responsiveness and EEG sleep criteria such
that some subjects remain fairly responsive during stage 1 sleep and others do not (Ogilvie et
al., 1989).
3.1.3.3. Subjective measures: During the sleep transition, there is increased self-report of
sleepiness and increased self-report of being asleep if aroused. Subjective sleepiness has been
evaluated with the Stanford sleepiness scale, Profile of Mood States, visual analog scale,
Epworth sleepiness scale (Johns, 1991) or Karolinska sleepiness scale (Akerstedt and Gillberg,
1990), with some of the measures geared towards longer assessment time periods.

Oken et al. Page 10
While there are correlations between the self-rated sleepiness scales and the EEG, self-reports
may not relate precisely to CNS state. Subjects are often still able to respond and may, in fact,
not report being asleep when awakened from stage 1 or even stage 2 sleep (Ogilvie and
Wilkinson, 1984). In one study, 25% of subjects awakened from clear stage 2 sleep reported
they had been awake (Hori, 1994) while another study reported the threshold of subjective
sleep (50% reporting being asleep) was 2–4 min after stage 2 onset (Bonnet and Moore,
1982). Also, self-reports of sleep may be altered in clinical situations: insomniacs were more
likely to report themselves as awake when actually awoken from stage 2 sleep than controls
(Moore et al., 1981). In terms of subjective experiences, arousals during this sleep onset period
can produce self-reports of sensory experiences that would appear to represent dreaming
(Foulkes and Vogel, 1965; Hori, 1994).
3.1.3.4. Conventional EEG measures of sleepiness: The most commonly used clinical EEG
measures of sleepiness are the multiple sleep latency test (MSLT) (Carskadon et al., 1986) and
the maintenance of wakefulness test (Mitler et al., 1982; Sangal et al., 1992) which both report
the mean length of time to sleep onset at multiple time periods. The awake maintenance task
is a modification of the maintenance of wakefulness test using only a single 6 min period
(Salinsky et al., 1996). These tests are sensitive to alterations in alertness secondary to
hypersomnias, sleep-deprivation, circadian rhythm, and drugs (Arand et al., 2005). Of interest,
some patients have different results on the two tests simply based on the instructional difference
to fall asleep or to stay awake (Sangal, 1992) and these tests and the Epworth sleepiness scale
may be assessing different subject characteristics (Johns, 2000). Sleepiness as assessed on these
tests correlates with performance on sustained attention tasks (Carskadon and Dement,
1979). However, the correlations are not great (George et al., 1996; Harrison and Horne,
1996), in part related to the lack of ideal definition of sleep onset, varying from a relatively
long, 3 consecutive 10-s epochs of stage 1 sleep to an epoch of stage 1 lasting several to 15 s
sometimes referred to as a microsleep (Doghramji et al., 1997; Salinsky, 1996; Valley and
Broughton, 1983). The lack of a very high correlation between sleepiness and vigilance
performance is also because inattention is only partially related to sleepiness (Sangal and
Sangal, 2004).
3.1.3.5. Physiological changes other than EEG: The transition from wakefulness to NREM
sleep is associated with a number of physiologic changes besides the EEG. One physiologic
change associated with state 1 sleep and formally included in staging is the presence of slow
lateral eye movements (Dement and Kleitman, 1957; Ogilvie et al., 1988; Rechtschaffen and
Kales, 1968). These slow eye movements (SEMs) may be maximal in an EEG defined awake
state with alpha still present and may be the first sign of decreased alertness in up to 50% of
subjects (Shimazono et al., 1965; Santamaria and Chiappa, 1987b). SEMs have been associated
with decreased performance (Torsvall and Akerstedt, 1987). Of note, SEMs decline again
during transition into stage 2 sleep (De Gennaro et al., 2000). While awake with eyes closed
there are fast eye movements and miniblinks that decrease during transition into state 1 and
may precede standard EEG markers for drowsiness (Santamaria and Chiappa, 1987a).
Decreased blink rate correlates with decreased performance on a sustained attention task (Van
Orden et al., 2000). While this decline in blink rate has not been consistently observed, observed
differences may be related to circadian changes in blink rate (Cajochen, 1999) and an increase
in blink flurries during sustained attention tasks (Stern et al., 1994) that may even serve as
some self-alerting mechanism. There is a decline in blink amplitude and an increase in blink
duration during sustained attention tasks that correlate with decreased performance (Morris
and Miller, 1996). Declines in eye movements that are presumably associated with refixations
are correlated with vigilance decrements during visual task performance (Mackworth et al.,
1964; Schroeder and Holland, 1968). Pupil size also decreases during drowsiness (Lowenstein
et al., 1963; McLaren et al., 1992; Yoss et al., 1970) and with decreased performance on a
sustained attention task (Van Orden, 2000). Frontalis EMG activity does not decrease

Oken et al. Page 11
significantly during sleep onset (Hauri and Good, 1974) although pharyngeal dilator EMG does
decrease (Mezzanotte et al., 1996).
There are physiologic changes affecting respiration and the autonomic nervous system in the
awake–sleep transition. There is a decrease in heart rate and this decrease may be seen even
prior to onset of stage 1 (Pivik and Busby, 1996) although the heart rate changes during
drowsiness are not great (Torsvall and Akerstedt, 1987; Welch and Richardson, 1973). The
heart rate decrease during the sleep onset period appears to relate to decreased sympathetic and
increased parasympathetic tone (Zemaityte and Varoneckas, 1984). There are also physiologic
changes in respiration. While there may be more rhythmic respirations during onset of sleep,
there is also a relative fall in abdominal respiration compared to thoracic, a decrease in tidal
volume, an increase in pCO2, a decrease in ventilatory responsiveness to hypercapnia and
hypoxia, and an increase in airflow resistance (Colrain et al., 1987; Colrain et al., 1990; Naifeh
and Kamiya, 1981; Ogilvie and Wilkinson, 1984; Trinder et al., 1992). The rhythmic deeper
respiration during the sleep onset period produces the expected increase in heart rate variability
measures secondary to sinus arrhythmia. There is also a decline in core body temperature
associated with an increase in peripheral temperature prior to sleep onset (Van Den Heuvel et
al., 1998).
Skin potential level and skin potential fluctuations recorded from the palm of the hand, but not
the dorsum of the hand, are related to EEG alertness levels and change even prior to onset of
stage 1 sleep (Hori, 1982). However, it should be noted that overall there may be changes in
spontaneous skin potentials and conductance measures during sleep that do not appear to relate
to alertness since there may be high activity even during slow wave sleep (Johnson and Lubin,
1966). The amount of spontaneous skin potentials prior to stimulus presentation may be
correlated with performance on a vigilance task (Surwillo and Quilter, 1965), but there is high
spontaneous variability.
3.2. Sleep loss

Sleep loss is an extremely common problem that may be caused by sleep deprivation or sleep
fragmentation. There is an extensive recent review literature on sleep deprivation (Durmer and
Dinges, 2005; Kusida, 2004a,b) so only selected portions of the literature related to topics
already mentioned are highlighted.
Insufficient overnight sleep time (average sleep length of < 6.5 h) is estimated to occur in about
1/3 of healthy young adults and a similar percentage have been found to have MSLT values
of < 7 min (normal >10 min) (Bonnet and Arand, 1995b, 2005; Levine, 1988). Sleep
fragmentation is also part of upper airway resistance syndrome and results in excessive daytime
sleepiness (Black et al., 2000; Bonnet and Arand, 2003; Guilleminault et al., 1993). Chronic
sleep loss also occurs in nightshift workers, rotating shift workers, and on-call workers, and is
compounded by circadian rhythm disturbances (Humphrey et al., 1994; Torsvall and Akerstedt,
1987, 1988a) reviewed in (Akerstedt, 1988). These problems alone or in combination are
cumulative for up to a week and beyond (Van Dongen et al., 2003). A ‘sleep debt’ is incurred
which results in cognitive and performance deficits, particularly during the overnight and
midday circadian peaks of sleep pressure (Mitler et al., 1988).
Sleep loss and drowsiness contribute significantly to accidents and impaired work
performance. Drowsiness is known to be a major factor in automobile crashes (Mitler, 1988)
reviewed in (George, 2004), with the incidence of crashes over the day being coincident with
the expected nadirs in circadian rhythm (Garbarino et al., 2001; Horne and Reyner, 1995;
Mitler, 1988). Even minor amounts of sleep deprivation may impair simulated driving
performance (Arnedt et al., 2001). Work errors have been related to sleep deprivation and shift
work (Akerstedt, 1988; Mitler, 1988; Mitler et al., 1997; Torsvall and Akerstedt, 1987,

Oken et al. Page 12
1988a). There are documented negative effects of sleep loss and shift work on medical
professionals (Cavallo et al., 2002; Friedman, 2004; Steele et al., 1999). Medical house staff
experience significant sleep deprivation and it is associated with EEG documented sleepiness
during eyes open periods during the night shift (Lockley et al., 2004; Richardson et al.,
1996). House staff have a significantly increased risk of motor vehicle accidents following a
night shift (Barger et al., 2005; Marcus and Loughlin, 1996; Steele, 1999).
3.2.1. Clinical effects—Overnight and partial night sleep deprivation are consistently
associated with excessive daytime sleepiness as measured by both subjective indices and the
MSLT (Beaumont et al., 2001; Bonnet and Arand, 1995a, 2003; Carskadon and Dement,
1982; Gillberg et al., 1994; Roehrs et al., 1989; Rosenthal et al., 1993). Sleepiness increases
in proportion to the total length of sleep deprivation (Rosenthal, 1993). There may be
differential effects based on the sleep stage of deprivation in that REM sleep deprivation does
not change MSLT scores (Nykamp et al., 1998). Sleep fragmentation (frequent brief
disruptions at regular intervals) similarly increases subjective daytime sleepiness, impairs
mood, and decreases MSLT times even when total sleep times are normal based on
conventional visual sleep scoring methods, and even if the arousals are subclinical (i.e. based
on EEG changes alone) (Bonnet and Arand, 2003; Cote et al., 2003; Kingshott et al., 2000;
Levine et al., 1987; Martin et al., 1996; Stepanski, 2002). Sleep interruptions may be as
infrequent as every 10 min yet still produce an effect on MSLT scores (Stepanski, 2002). The
effects of sleep deprivation are cumulative, up to a week and beyond of partial sleep deprivation
(Carskadon, 1981; Dinges et al., 1997; Van Dongen, 2003).
The effects of sleep deprivation on performance tests have been extensively studied,
particularly effects on reaction time (RT) and sustained attention tests including driving
simulation reviewed in (Dinges, 1992). RT lengthens with even partial sleep deprivation, and
there is a progressive lengthening of RT with longer deprivation periods (Beaumont, 2001;
Cochran et al., 1992; Dinges, 1997; Doran et al., 2001; Downey and Bonnet, 1987; Gauthier
and Gottesmann, 1983; Gillberg, 1994; Humphrey, 1994; Koslowsky and Babkoff, 1992;
Lorenzo et al., 1995; Magill et al., 2003; Pilcher and Huffcutt, 1996; Smith et al., 2002;
Wesenten et al., 2002; Wilkinson, 1965). Similar findings are seen with classic tests of
vigilance using long, repetitive tasks in which there is a signal detection component (Akerstedt,
1988; Gillberg, 1994; Magill, 2003; Strauss et al., 1984; Van Dongen et al., 2001, 2004;
Wilkinson, 1965). Vigilance tasks show longer RTs and increased errors of omission at longer
time intervals, consistent with the results of the shorter duration RT tests. The effect of sleep
deprivation on RT and vigilance tasks represents both an increase in average RT and a
lengthening of the right tail of the RT distribution with an increased coefficient of variability
(Smith, 2002; Wilkinson, 1965). The latter effect has been thought to represent brief lapses in
attention which lead to errors of omission or very long RTs (gaps or lapses), and may be related
to brief sleep episodes lasting several to 15 s (microsleeps) (Johnson et al., 1990; Koslowsky
and Babkoff, 1992; McCarthy and Waters, 1997; Wilkinson, 1965). Both task duration and
length of sleep deprivation have significant effects on performance (Gillberg, 1994; Lorenzo,
1995; Smith, 2002; Steyvers and Gaillard, 1993; Wilkinson, 1965). For example, Lorenzo et
al. (1995) demonstrated a linear trend of increased RT and increased omissions (lapses) over
a 40 h period of sleep deprivation (Lorenzo, 1995). Also, there is an interaction between the
task duration and length of sleep deprivation on performance such that shorter task durations
may not be as sensitive to equivalent lengths of sleep deprivation (Caldwell and Ramspott,
1998).
Several factors modify the effects of sleep deprivation on RT and vigilance task performance.
Long, simple, low-interest, self-paced RT tests are most affected by sleep loss (Wilkinson,
1965). The effects of sleep deprivation on RT are partially reversed when there is feedback
provided, when the task is shorter or more challenging, or when there is a reward used as

Oken et al. Page 13
incentive for performance, suggesting that increased motivation or interest can at least partially
compensate for the effects of sleep deprivation (Steyvers and Gaillard, 1993; Wilkinson,
1965). This motivational effect may be similar to the improvement in vigilance performance
that occurs when subjects know they are approaching the end of the task (end-spurt effect)
(Bergum and Lehr, 1963). The increase in RT is greater when there is a relatively long interval
between a warning signal and the imperative stimulus, less if the interval is short, suggesting
that phasic arousal or alertness deteriorates quickly under sleep deprivation (Cochran, 1992).
RT performance in overnight sleep deprived subjects is slowed when seated, but normal when
standing (Caldwell et al., 2002). The effects of sleep deprivation are complicated by the
interaction of diurnal variation (circadian phase) with monotonic effects (length of sleep
deprivation), consistent with the two-process model proposed by Borbely (Achermann and
Borbely, 2003; Babkoff et al., 1991; Cajochen, 1999). Also, effects of sleep deprivation on
performance are not uniform and there is considerable intersubject variability, likely
representing individual characteristics (Bonnet and Arand, 2005; Van Dongen, 2004).
The effects of sleep deprivation on other cognitive tasks have been less consistent than effects
on RT and vigilance tasks. To some extent this lack of consensus is due to different
experimental conditions and study designs (length of sleep deprivation, length of testing
battery, difficulty of the task, etc.). For example, Stroop performance change was affected by
the pattern of sleep deprivation (Beaumont, 2001; Binks et al., 1999; Herscovitch et al.,
1980). Variable effects on memory may be related to task difficulty (Cajochen, 1999; Harrison
et al., 2000; Humphrey, 1994; Linde and Bergstrom, 1992; McCarthy and Waters, 1997; Smith,
2002). Significant effects have also been demonstrated on the Sternberg working memory task
and were correlated with decreased fMRI activation in multiple brain areas, particularly the
bilateral parietal cortices (Mu et al., 2005). Sleep deprivation effects on Raven’s matrices
(Linde and Bergstrom, 1992), verbal fluency (Horne, 1988), Tower of London (non-verbal
planning) (Horne, 1988), Paced auditory serial addition test (Martin, 1996), and Trails B
(Martin, 1996), have been reported. The effect of sleep fragmentation on cognitive abilities is
generally less pronounced than the effects of sleep deprivation, despite similar effects on MSLT
scores (Cote, 2003; Kingshott, 2000; Philip et al., 1994; Stepanski, 2002).
Measures of subjective sleepiness (the Karolinska sleepiness scale or the Stanford sleepiness
scale) are generally sensitive to decreased alertness and performance decrements during sleep
deprivation but are poorly correlated to performance on RT, vigilance and cognitive tasks in
individuals (Binks, 1999; Gillberg, 1994; Herscovitch and Broughton, 1981). A meta-analysis
emphasized that although motor and cognitive tasks are generally affected by sleep deprivation,
subjective mood measures showed the greatest effects (Pilcher and Huffcutt, 1996).
3.2.2. Electrophysiological measures

3.2.2.1. EEG: As already described, the transition from the awake to the sleep state involves
several EEG changes including slowing and anteriorization of the dominant posterior rhythm,
an increase in fronto- central theta power, a reduction in eye blinks followed by increasing
amounts of slow eye movements, and eventually attenuation of the posterior dominant rhythm,
and development of vertex sharp waves. These features are also seen with sleep deprivation.
During and following sleep deprivation there is a progressive increase in absolute power and
in relative theta and delta power in the EEG background, accompanied by an increase in slow
eye movements, and correlated with subjective sleepiness (Caldwell, 2002; Cajochen et al.,
1995; Lorenzo, 1995; Smith, 2002; Torsvall and Akerstedt, 1988b). This EEG slowing
gradually increases until the sleep deprived subject dozes off (Torsvall and Akerstedt,
1988b). This phenomenon has been observed in train drivers on the job, with correlation to
subjective sleepiness and driving errors (Torsvall and Akerstedt, 1987). The increase in
absolute power is related to slowing of RT and increased errors on a vigilance task (Corsi-

Oken et al. Page 14
Cabrera, et al. 1996; Lorenzo, 1995). Standing upright attenuates the increase in theta activity
seen with sleep deprivation (along with RT changes; see above) (Caldwell, 2002). Awake EEG
changes are also seen following sleep fragmentation despite normal total sleep time. A decrease
in the alpha:theta ratio was observed following a single night of sleep fragmentation, increased
following a second night, and correlated with subjective complaints despite a lack of significant
effect on performance measures (Cote, 2003). Although sleep deprivation reliably produces
effects on the EEG power spectrum and task performance, there is no effect on task related
frontal midline theta activity (Smith, 2002).
The increase in EEG frontal slow wave activity following sleep deprivation appears to be
independent of circadian variation (Cajochen, 1999). However, in the same experiment
neurobehavioral measures (vigilance RT, short-term memory) showed circadian effects with
deterioration following melatonin secretion (after about 16 h of wakefulness). These
neurobehavioral changes correlated with an increase in slow eye movements, and changes in
the dominant posterior rhythm suggesting that some EEG components are phase locked to the
circadian cycle whereas others are not (Cajochen, 1999). Increased frontal slow activity is a
prominent feature in the sleep deprived EEG, lending some support to the hypothesis that
frontal regions are more susceptible to sleep deprivation effects than other brain regions
(Cajochen, 1999; Horne, 1993). During slow wave sleep cerebral blood flow (measured by
positron emission tomography) in the orbitofrontal and anterior cingulate cortex is negatively
correlated with EEG delta activity (Hofle et al., 1997).
EEG has also been used to study the dynamics of the decreased performance associated with
sleep deprivation. During an auditory vigilance task, there was a pattern of increased near 4
Hz (low) theta and decreased near 40 Hz gamma during missed targets (lapses) with the
opposite pattern during accurate target detections (hits) (Makeig and Jung, 1996). The increase
in low theta power with poor performance was subsequently confirmed in a more difficult
continuous performance task using subjects studied throughout 42 h of sleep deprivation
(Makeig et al., 2000). Both studies revealed a periodicity of about 18 s for both performance
and EEG low theta activity during periods of relatively poor performance related to drowsiness,
with the two measures correlated to one another (Makeig and Jung, 1996; Makeig, 2000).
Following overnight or diurnal sleep there is an increase in interhemispheric correlations as
compared to presleep baseline, with the opposite effect seen after a night of sleep deprivation
(Corsi-Cabrera et al., 1992). All of these EEG changes are associated with functional
impairment and therefore have potential practical applications for monitoring performance
(Corsi-Cabrera, 1992; Jung, 1997).
3.2.2.2. Event related potentials

3.2.2.2. Event related potentials: P3: Long latency ERPs have primarily been used as a
measure of phasic attention. The latency of the P3 potential increases, and the amplitude
decreases, progressively during overnight sleep deprivation, suggesting problems with
stimulus evaluation and attention (Humphrey, 1994; Lorist et al., 1994; Morris et al., 1992;
Smith, 2002). These changes can be seen even in the absence of RT changes (Morris, 1992).
However, the largest reductions in P3 amplitude correlated with increased RT, decreased
response accuracy, and increased response variability (Smith, 2002). It is unclear whether the
decrease in P3 amplitude and increase in latency are manifestations of a decreased magnitude
of response or a greater variability in response. Results with sleep fragmentation (preserving
total sleep time) are inconsistent, with one study showing a decrease in amplitude without
change in latency, and another showing no change in either parameter (Cote, 2003; Kingshott,
2000).

Oken et al. Page 15
VEP: Overnight sleep deprivation induced a progressive reduction in amplitude and increase
in latency of the late components of the visual evoked potential (P180 and beyond) obtained
during a visual vigilance task (Corsi-Cabrera et al., 1999). The late component was consistent
with the time window for the N2 potential which correlates with the decision process for RT
(Ritter et al., 1979). Early components (P100) were unchanged, suggesting that processes
affected were for sensory discrimination and target selection. In the course of a 100 min visual
vigilance task (light flashes), the amplitude of the N160 potential decreased and its latency
progressively increased in correlation with the number of detection failures (Haider, 1964).
Averages from the detection failures showed much greater attenuation, the electrophysiologic
correlate of behavioral ‘lapses’ as defined above. In an n-back visual working memory task
the N170 was slowed and attenuated by sleep deprivation suggesting an effect on ‘selective
focusing of attention onto particular stimulus attributes’ (Smith, 2002).
AEP (N1, P1): The latencies of the P1 and N1 auditory evoked potentials were increased, and
the N1 amplitude reduced, following 48 h of sleep deprivation, suggesting that there is a delay
in sensory encoding processes (Cote, 2003; Gauthier and Gottesmann, 1983). N1 amplitude
was also mildly reduced after 1 and 2 nights of sleep fragmentation, though P3 was unaffected
(Cote, 2003).
Twenty-four to thirty-six h of sleep deprivation also produces a mild but significant decrease
in the amplitude of auditory mismatch negativity (a potential related to deviant stimuli in a
non-attended train), while the N1 potential was preserved (Raz et al., 2001). This suggests that
while sensory encoding was intact a later process is affected, possibly one related to the
transient (reflexive) capture of attention.
Contingent negative variation. Contingent negative variation was reduced in amplitude and
increased in variability following 24–48 h of sleep deprivation (Gauthier and Gottesmann,
1983; Naitoh, 1971). It is unclear whether this is an effect on sleep deprivation on attention or
a non-specific effect on arousal (Gauthier and Gottesmann, 1983).
3.2.3. Sleep deprivation summary—In summary, there is extensive behavioral and

electro-physiologic evidence that sleep deprivation or fragmentation impairs brain function.
The effects are at least partly mediated by decreased arousal (represented by EEG) and
increased sleep pressure leading to inconsistent performance (greater response variability with
lapses on RT and sustained attention tests). The effects on performance are mirrored by brief
intrusions of drowsy features into the waking EEG (microsleeps), eventually building to a more
continuous drowsy pattern. There also appears to be a significant effect of sleep deprivation
on ERPs. These include effects on initial sensory encoding (auditory N1, in some studies), and
more consistent effects on later potentials believed to represent attentional processes involved
with stimulus discrimination (N2, N170, P3).
4. Conclusions
There are a number of neural and functional systems relatively directly affecting phasic and
tonic alertness. In addition, there are a number of systems that directly modulate these alertness
systems, such as the neural systems related to motivation and stress. The multiple constructs
and neural systems underlying the relatively non-specific phasic and tonic alertness activation
states imply that they are not unidimensional. Thus, one should rarely, if ever, simplify and
speak about vigilance or alertness on a unidimensional continuum, When studying these
activation states, one should try to experimentally control and report on as many parameters
and utilize as many specific physiologic or behavioral measurements as possible. Recruitment
strategies and performance incentives should be fully described. While there are discrete state

Oken et al. Page 16
changes, when studying transitional and pathologic states it is apparent that these activation
states function on a continuum.
The field has been hindered by inconsistent or poorly defined terminology. Researchers should
be particularly careful about the usage of the term vigilance, understanding there are factors
contributing to vigilance other than just arousal on the sleep–wake dimension. Avoidance of
the term vigilance because of its varied definitions would be most helpful. The use of the term
tonic alertness may be preferable since it does not already have a confusing history. Whatever
terms are used should be operationally defined in order to avoid impeding progress in our
understanding of these important topics. Future studies should continue to incorporate analysis
of finer temporal aspects of physiologic-performance relationships, and not simpy averaging
both over many minutes. Other helpful research may include trying to better ascertain the
contributions of other neural systems that may impact on vigilance, including stress,
motivation, and novelty. It is likely that some of the variability of research results to date relates
to inadequate control of these aspects. Neural systems related to stress are important clinically
and studying the modulation of alertness and performance by stress may be particularly useful.
Acknowledgments
Supported in part by NIH AT002656 and AT01993.
References
Achermann P, Borbely A. Mathematical models of sleep regulation. Front Biosci 2003;6:683–693.
Akerstedt T. Sleepiness as a consequence of shift work. Sleep 1988;11:17–34. [PubMed: 3283910]
Akerstedt T, Gillberg M. Subjective and objective sleepiness in the active individual. Int J Neurosci
1990;52(1–2):29–37. [PubMed: 2265922]
Akerstedt, T.; Torsvall, L.; Gillberg, M. Shift work and napping. In: Dinges, DF.; Broughton, RJ., editors.
Sleep and alertness: chronobiological, behavioral, and medical aspects of napping. New York: Raven
Press; 1989. p. 205-220.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed..
Washington, D.C: American Psychiatric Association; 1994.
Arand D, Bonnett M, Hurwitz T, Mitler M, Rosa R, Sangal RB. The clinical use of the MSLT and MWT.
Sleep 2005;28:123–144. [PubMed: 15700728]
Arnedt J, Wilde G, Munt P, MacLean A. How do prolonged wakefulness and alcohol compare in the
decrements they produce on a simulated driving task? Accid Anal Prev 2001;33:337–344. [PubMed:
11235795]
Aston-Jones G, Bloom FE. Activity of norepinephrine-containing locus coeruleus neurons in behaving
rats anticipates fluctuations in the sleep-waking cycle. J Neurosci 1981a;1:876–886. [PubMed:
7346592]
Aston-Jones G, Bloom FE. Nonrepinephrine-containing locus coeruleus neurons in behaving rats exhibit
pronounced responses to non-noxious environmental stimuli. J Neurosci 1981b;1(8):887–900.
[PubMed: 7346593]
Aston-Jones G, Rajkowski J, Kubiak P, Alexinsky T. Locus coeruleus neurons in monkey are selectively
activated by attended cues in a vigilance task. J Neurosci 1994;14(7):4467–4480. [PubMed: 8027789]
Babkoff H, Caspy T, Mikulincer M, Sing H. Monotonic and rhythmic influences: a challenge for sleep
deprivation research. Psychological Bulletin 1991;109:411–428. [PubMed: 2062980]
Barger LK, Cade BE, Ayas NT, Cronin JW, Rosner B, Speizer FE, Czeisler CA. Harvard Work Hours,
Health, and Safety Group. Extended work shifts and risk of motor vehicle crashes among interns. N
Engl J Med 2005;352:125–134. [PubMed: 15647575]
Barkley RA, Grodzinsky G, DuPaul GJ. Frontal lobe functions in attention deficit disorder with and
without hyperactivity: a review and research report. J Abnorm Child Psychol 1992;20(2):163–188.
[PubMed: 1593025]

Oken et al. Page 17
Beaumont M, Batejat D, Pierard C, Coste O, Doireau P, Van Beers P, Chauffard F, Chassard D, Enslen
M, Denis JB, Lagarde D. Slow release caffeine and prolonged (64-h) continuous wakefulness: effects
on vigilance and cognitive performance. J Sleep Res 2001;10:265–276. [PubMed: 11903856]
Begleiter H, Porjesz B, Chou CL, Aunon JI. P3 and stimulus incentive values. Psychophysiology 1983;20
(1):95–101. [PubMed: 6828618]
Belyavin A, Wright NA. Changes in electrical activity of the brain with vigilance. Electroencephalogr
Clin Neurophysiol 1987;66(2):137–144. [PubMed: 2431878]
Bennett LS, Stradling JR, Davies RJ. A behavioural test to assess daytime sleepiness in obstructive sleep
apnoea. J Sleep Res 1997;6(2):142–145. [PubMed: 9377534]
Bergum BO, Lehr DJ. End-spurt in vigilance. J Exp Psychol 1963;66:383–385. [PubMed: 14051853]
Bernston GG, Caciollo JT, Quigley KS. Autonomic determinism. The modes of autonomic control, the
doctrine of autonomic space, and the laws of autonomic constraint. Psychol Rev 1991;98:459–487.
[PubMed: 1660159]
Berridge C, Waterhouse B. The locus coeruleus-noradrenergic system: modulation of behavioral state
and state-dependent cognitive process. Brain Res Rev 2003;42:33–84. [PubMed: 12668290]
Berridge CW, Page ME, Valentino RJ, Foote SL. Effects of locus coeruleus inactivation on
electroencephalographic activity in neocortex and hippocampus. Neuroscience 1993;55(2):381–393.
[PubMed: 8104319]
Binks P, Waters W, Hurry M. Short term total sleep deprivation does not slelctively impair higher cortical
functioning. Sleep 1999;22:328–334. [PubMed: 10341383]
Black J, Guilleminault C, Colrain I, Carrillo O. Upper airway resistance syndrome: central
electroencephalographic power and changes in breathing effort. Am J Respir Crit Care Med
2000;162:406–411. [PubMed: 10934061]
Boddy J. The relationship of reaction time to brain wave period. Electroencephalogr Clin Neurophysiol
1971;30:229–235. [PubMed: 4103145]
Bonnet M, Arand D. The consequences of a week of insomnia. Sleep Research 1995a;24:201.
Bonnet M, Arand D. We are chronically sleep deprived. Sleep 1995b;18:908–911. [PubMed: 8746400]
Bonnett MH, Arand DL. Sleepiness as measured by MSLT varies as a function of preceding activity.
Sleep 1998;21:477–483. [PubMed: 9703587]
Bonnet MH, Arand DL. Clinical effects of sleep fragmentation versus sleep deprivation. Sleep Med Rev
2003;7(4):297–310. [PubMed: 14505597]
Bonnet M, Arand D. Performance and cardiovascular measures in normal adults with extreme MSLT
scores and subjective sleepiness levels. Sleep 2005;28:685–693. [PubMed: 16477955]
Bonnet M, Moore S. The threshold of sleep: perception of sleep as a function of time asleep and auditory
threshold. Sleep 1982;5(3):267–276. [PubMed: 7134732]
Caggiano DM, Parasuraman R. The role of memory representation in the vigilance decrement. Psychon
Bull Rev 2004;11(5):932–937. [PubMed: 15732706]
Cajochen C, Brunner D, Krauchi K, Graw P, Wirz-Justice A. Power density in the theta/alpha frequencies
of the waking EEG progressively increases during sustained wakefulness. Sleep 1995;18:890–894.
[PubMed: 8746397]
Cajochen C, Khalsa SBS, Wyatt JK, Czeisler CA, Dijk D-J. EEG and ocular correlates of circadian
melatonin phase and human performance decrements during sleep loss. Am J Physiol
1999;277:R640–R649. [PubMed: 10484479]
Caldwell JA, Ramspott S. Effects of task duration on sensitivity to sleep deprivation using the multi-
attribute task battery. Behav Res Methods Instrum Comput 1998;30(4):651–660.
Caldwell J, Prazinko B, Caldwell J. Body posture affects electroencephalographic activity and
psychomotor vigilance task performance in sleep-deprived subjects. Clin Neurophysiol
2002;114:23–31. [PubMed: 12495760]
Carskadon M. Cumulative effects of sleep restriction on daytime sleepiness. Psychophysiology
1981;18:107–113. [PubMed: 6111825]
Carskadon M, Dement W. Nocturnal determinants of daytime sleepiness. Sleep 1982;5:s73–s81.
[PubMed: 7156657]

Oken et al. Page 18
Carskadon MA, Dement WC. Effects of total sleep loss on sleep tendency. Percept Mot Skills 1979;48
(2):495–506. [PubMed: 461051]
Carskadon MA, Dement WC, Mitler MM, Roth T, Westbrook PR, Keenan S. Guidelines for the multiple
sleep latency test (MSLT): a standard measure of sleepiness. Sleep 1986;9(4):519–524. [PubMed:
3809866]
Cavallo A, Jaskiewicz J, Ris M. Impact of night-float rotation on sleep, mood, and alertness: the resident’s
perception. Chronobiology International 2002;19:893–902. [PubMed: 12405552]
Celesia GG, Jasper HH. Acetylcholine release from cerebral cortex in relation to state of activation.
Neurology 1966;16(11):1053–1063. [PubMed: 5950916]
Cochran J, Thorne D, Penetar D, Newhouse P. Parsing attentional components during a simple reaction
time task using sleep deprivation and amphetamine intervention. Percept Mot Skills 1992;75:675–
689. [PubMed: 1454457]
Colrain IM, Trinder J, Fraser G, Wilson GV. Ventilation during sleep onset. J Appl Physiol
1987;63:2067–2074. [PubMed: 3693239]
Colrain IM, Trinder J, Fraser G. Ventilation during sleep onset in young adult females. Sleep 1990;13
(6):491–501. [PubMed: 2281248]
Conte S, Ferlazzo F, Renzi P. Ultradian rhythms of reaction times in performance in vigilance tasks. Biol
Psychol 1995;39(2–3):159–172. [PubMed: 7734628]
Corsi-Cabrera M, Ramos J, Arce C, Guevara M, Ponce-de Leon M, Lorenzo I. Changes in the waking
EEG as a consequence of sleep and sleep deprivation. Sleep 1992;15:550–555. [PubMed: 1475570]
Corsi-Cabrera M, Ramos C, Lorenzo I, Guevara M. Time course of reaction time and EEG while
performing a vigilance task during total sleep deprivation. Sleep 1996;19:563–569. [PubMed:
8899935]
Corsi-Cabrera M, Arce C, Del Rio-Portilla I, Perez-Garci E, Guevara M. Amplitude reduction in visual
evoked potentials as a function of sleep deprivation. Sleep 1999;22:181–189. [PubMed: 10201062]
Cote K, Milner C, Osip S, Ray L, Baxter K. Waking quantitative electroencephalogram and auditory
event-related potentials following experimentally induced sleep fragmentation. Sleep 2003;26:687–
694. [PubMed: 14572121]
Dalley JW, Theobald DE, Bouger P, Chudasama Y, Cardinal RN, Robbins TW. Cortical cholinergic
function and deficits in visual attentional performance in rats following 192 igg-saporin-induced
lesions of the medial prefrontal cortex. Cerebral Cortex 2004;14(8):922–932. [PubMed: 15084496]
Davies, DR.; Parasuraman, R. The psychology of vigilance. London: Academic Press; 1982.
Davis M, Whalen PJ. The amygdala: vigilance and emotion. Mol Psychiatry 2001;6(1):13–34. [PubMed:
11244481]
De Gennaro L, Ferrara M, Ferlazzo F, Bertini M. Slow eye movements and EEG power during wake-
sleep transition. Clin Neurophysiol 2000;111(12):2107–2115. [PubMed: 11090759]
de Lecea L, Kilduff TS, Peyron C, Gao X-B, Foye PE, Danielson PE, Fukuhara C, Battenberg ELF,
Gautvik VT, Bartlett IIFS, Frankel WN, van den pol AN, Bloom FE, Gautvik KM, Sutcliffe JG. The
hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA
1998;95(1):322–327. [PubMed: 9419374]

Dement W, Kleitman N. Cyclic variations in EEG during sleep and their relation to eye movements, body
motility, and dreaming. Electroencephalogr Clin Neurophysiol 1957;9(4):673–690. [PubMed:
13480240]
Dijk DJ, Czeisler CA. Contribution of the circadian pacemaker and the sleep homeostat to sleep
propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in
humans. J Neurosci 1995;15:3526–3538. [PubMed: 7751928]
Dinges, D. Sleep, arousal, and performance. Boston: Birkhauser; 1992. Probing the limits of functional
capability: the effects of sleep loss on short-duration tasks; p. 176-188.
Dinges D, Pack F, Williams K, Gillen KA, Powell JW, Ott GE, Aptowicz C, Pack AI. Cumulative
sleepiness, mood disturbance, and psychomotor vigilance performance decrements during a week of
sleep restricted to 4–5 hours per night. Sleep 1997;20:267–277. [PubMed: 9231952]
Doghramji K, Mitler MM, Sangal RB, Shapiro C, Taylor S, Walsleben J, Belisle C, Erman MK, Hayduk
R, Hosn R, O’Malley EB, Sangal JM, Schutte SL, Youakim JM. A normative study of the

Oken et al. Page 19
maintenance of wakefulness test (MWT). Electroencephalogr Clin Neurophysiol 1997;103(5):554–

562. [PubMed: 9402886]
Doran S, Van Dongen H, Dinges D. Sustained attention performance during sleep deprivation: evidence
of state instability. Arch Ital Biol 2001;139:253–267. [PubMed: 11330205]

Downey R, Bonnet M. Performance during frequent sleep disruptions. Sleep 1987;10:354–363. [PubMed:
3659733]
Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation. Seminars Neurology
2005;25:117–129.
Eeg-Olofsson O. The development of the electroencephalogram in normal children and adolescents from
the age 1 through 21 years. Acta Paediatr Scand 1971;208:1–46.
Engleman H, Martin S. Effect of continuous positive airway pressure treatment on daytime function in
sleep apnoea/hypopnoea syndrome. Lancet 1994;343(8897):572–575. [PubMed: 7906330]
Everitt BJ, Robbins TW. Central cholinergic systems and cognition. Annu Rev Psychol 1997;48:649–
684. [PubMed: 9046571]
Ferrara M, De Gennaro L, Bertini M. Time-course of sleep inertia upon awakening from nighttime sleep
with different sleep homeostasis conditions. Aviat Space Environ Med 2000;71:225–229. [PubMed:
10716166]
Fisk A, Schneider W. Control and automatic processing during tasks requiring sustained attention: a new
approach to vigilance. Human Factors 1981;23(6):737–750.
Foulkes D, Vogel G. Mental activity at sleep onset. J Abnorm Psychol 1965;70:231–243. [PubMed:
14341704]
Friedman W. Resident duty hours in neurosurgery. Neurosurgery 2004;54:925–931. [PubMed:

15046659]
Gallassi R, Morreale A, Montagna P, Gambetti P, Lugaresi E. Fatal familial insomnia:
neuropsychological study of a disease with thalamic degeneration. Cortex 1992;28(2):175–187.
[PubMed: 1499304]
Garbarino S, Nobili L, Beelke M. The contributing role of sleepiness in highway vehicle accidents. Sleep
2001;24:203–206. [PubMed: 11247057]
Gauthier P, Gottesmann C. Influence of total sleep deprivation on event-related potentials in man.
Psychophysiology 1983;20:351–355. [PubMed: 6867228]
George C. Driving and automobile crashes in patients with obstructive sleep apnea/hypopnea syndrome.
Thorax 2004;59:804–807. [PubMed: 15333860]
George CF, Boudreau AC, Smiley A. Comparison of simulated driving performance in narcolepsy and
sleep apnea patients. Sleep 1996;19(9):711–717. [PubMed: 9122558]
Gevins A, Smith M, McEvoy L, Yu D. High resolution EEG mapping of cortical activation related to
working memory: effects of task difficulty, type of processing, and practice. Cerebral Cortex 1997a;
7:374–385. [PubMed: 9177767]
Gevins AS, Zeitlin GM, Ancoli S, Yeager CL. Computer rejection of EEG artifact. Ii. Contamination by
drowsiness. Electroencephalogr Clin Neurophysiol 1977b;43(1):31–42. [PubMed: 68870]
Gevins AS, Morgan NH, Bressler SL, Cutillo BA, White RM, Illes J, Greer DS, Doyle JC, Zeitlin GM.
Human neuroelectric patterns predict performance accuracy. Science 1987;235:580–585. [PubMed:
3810158]
Gill TM, Sarter M, Givens B. Sustained visual attention performance-associated prefrontal neuronal
activity: evidence for cholinergic modulation. J Neurosci 2000;20:4745–4757. [PubMed: 10844044]
Gillberg M, Kecklund G, Akerstedt T. Relations between performance and subjective ratings of sleepiness
during a night awake. Sleep 1994;17(3):236–241. [PubMed: 7939123]
Griesar WS, Zajdel DP, Oken BS. Nicotine effects on alertness and spatial attention in non-smokers.
Nicotine Tob Res 2002;4:185–194. [PubMed: 12028851]
Gross J, Schmitz F, Schnitzler I, Kessler K, Shapiro K, Hommel B, Schnitzler A. Modulation of long-
range neural synchrony reflects temporal limitations of visual attention in humans. PNAS
2004;101:1350–1355. [PubMed: 14745017]

Oken et al. Page 20
Grottick AJ, Haman M, Wyler R, Higgins GA. Reversal of a vigilance decrement in the aged rat by
subtype-selective nicotinic ligands. Neuropsychopharmacology 2003;28(5):880–887. [PubMed:
12637951]
Guilleminault C, Stoohs R, Clerk A, Cetel M, Maistros P. A cause of excessive daytime sleepiness: the
upper airway resistance syndrome. Chest 1993;104:781–787. [PubMed: 8365289]
Haider M, Spong P, Lindsley DB. Attention, vigilance, and cortical evoked-potentials in humans. Science
1964;145:180–182. [PubMed: 14171563]
Hancock PA, Warm JS. A dynamic model of stress and sustained attention. Human Factors 2003;31(5):
519–537. [PubMed: 2625347]
Harrison Y, Horne JA. High sleepability without sleepiness. The ability to fall asleep rapidly without
other signs of sleepiness. Neurophysiol Clin 1996;26(1):15–20. [PubMed: 8657094]
Harrison Y, Horne J, Rothwell A. Prefrontal neuropsychological effects of sleep deprivation in young
adults—a model for healthy ageing? Sleep 2000;23:1–7.
Hauri P, Good R. Frontalis muscle tension and sleep onset. Sleep Res 1974;4:222.
Herscovitch J, Broughton R. Sensitivity of the stanford sleepiness scale to the effects of cumulative partial
sleep deprivation and recovery oversleeping. Sleep 1981;4:83–92. [PubMed: 7232973]
Herscovitch J, Stuss D, Broughton R. Changes in cognitive processing following short-term cumulative
partial sleep deprivation and recovery oversleeping. J Clin Neuropsychol 1980;2:301–319.
Hofle N, Paus T, Reutens D, Hofle N, Paus T, Reutens D, Fiset P, Gotman J, Evans AC, Jones BE.
Regional cerebral blood flow changes as a function of delta and spindle activity during slow wave
sleep in humans. J Neurosci 1997;17:4800–4808. [PubMed: 9169538]
Hömberg V, Grnewald G, Grnewald-Zuberbier E. The variation of p300 amplitude in a money winning

paradigm in children. Psychophysiology 1981;18(3):258–262. [PubMed: 7291442]
Hori T. Electrodermal and electro-oculographic activity in a hypnagogic state. Psychophysiology 1982;19
(6):668–672. [PubMed: 7178384]
Hori, T.; Hayashi, M.; Morikawa, T. Topographic EEG changes and the hypnagogic experience. In:
Ogilvie, R.; Harsh, J., editors. Sleep onset: normal and abnormal processes. Washington, DC:
American Psychological Association; 1994. p. 237-254.
Horne J. Sleep loss and "divergent" thinking ability. Sleep 1988;11:528–536. [PubMed: 3238256]
Horne J. Human sleep, sleep loss and behaviour: implications for the prefrontal cortex and psychiatric
disorder. Br J Psychiatry 1993;162:413–419. [PubMed: 8453439]
Horne J, Reyner L. Sleep related vehicle accidents. Br Med J 1995;310:565–567. [PubMed: 7888930]
Humphrey D, Kramer A, Stanny R. Influence of extended wakefulness on automatic and nonautomatic
processing. Human Factors 1994;36:652–669. [PubMed: 7875692]
Ishii R, Shinosaki K, Ukai S, Inouye T, Ishihara T, Yoshimine T, Hirabuki N, Asada H, Kihara T,
Robinson SE, Takeda M. Medial prefrontal cortex generates frontal midline theta rhythm. Cogn
Neurosci 1999;10:657–679.
Jensen O, Tesche C. Frontal theta activity in humans increases with memory load in a working memory
task. Eur J Neurosci 2002;15:1395–1399. [PubMed: 11994134]
Jewett M, Wyatt J, Ritz-De Cecco A, Bir Khalsa S, Dijk D, Czeisier C. Time course of sleep inertia
dissipation in human performance and alertness. J Sleep Res 1999;8:1–8. [PubMed: 10188130]
Johns MW. A new method for measuring daytime sleepiness: the epworth sleepiness scale. Sleep 1991;14
(6):540–545. [PubMed: 1798888]
Johns MW. Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of
wakefulness test and the epworth sleepiness scale: failure of the MSLT as a gold standard. J Sleep
Res 2000;9(1):5–11. [PubMed: 10733683]
Johnson LC, Lubin A. Spontaneous electrodermal activity during waking and sleeping.
Psychophysiology 1966;3(1):8–17. [PubMed: 5942878]
Johnson L, Spinweber C, Gomez S. Benzodiazepines and caffeine: effect on daytime sleepiness,
performance, and mood. Psychophysiology 1990;101:160–167.
Jung TP, Makeig S, Stensmo M, Sejnowski TJ. Estimating alertness from the EEG power spectrum. IEEE
Trans Biomed Eng 1997;44(1):60–69. [PubMed: 9214784]
Kahneman, D. Attention and effort. Englewood Cliffs, NJ: Prentice-Hall; 1973.

Oken et al. Page 21
Kaiser J, Lutzenberger W. Human gamma-band activity: a window to cognitive processing. Neuroreport

2004;16:207–211. [PubMed: 15706221]
Kingshott R, Cosway R, Deary I, Douglas N. The effect of sleep fragmentation on cognitive processing
using computerized topographic brain mapping. J Sleep Res 2000;9:353–357. [PubMed: 11386203]
Kornfeld C, Beatty J. EEG spectra during a long-term compensatory tracking task. Bull Psychon Soc
1977;10(1):46–48.
Koslowsky M, Babkoff H. Meta-analysis of the relationship between total sleep deprivation and
performance. Chronobiol Int 1992;9:132–136. [PubMed: 1533178]
Krieger AC, Ayappa I, Norman RG, Rapoport DM, Walsleben J. Comparison of the maintenance of
wakefulness test (MWT) to a modified behavioral test (osler) in the evaluation of daytime
sleepiness. J Sleep Res 2004;13(4):407–411. [PubMed: 15560775]
Kusida, CA. Sleep deprivation: basic science, physiology, and behavior. New York: Marcel Dekker;
2004a.
Kusida, CA. Sleep deprivation: clinical issues, pharmacology, and sleep loss effects. New York: Marcel
Dekker; 2004b.
Lachaux J-P, Rodriguez E, Martinerie J, Varela F. Measuring phase synchrony in brain signals. Human
Brain Mapping 1999;8:194–208. [PubMed: 10619414]
Lambe EK, Olausson P, Horst NK, Taylor JR, Aghajanian GK. Hypocretin and nicotine excite the same
thalamocortical synapses in prefrontal cortex: correlation with improved attention in rat. J Neurosci
2005;25:5225–5229. [PubMed: 15917462]
Le Van Quyen M, Foucher J, Lachaux J-P, Rodriguez E, Lutz A, Martinerie J, Varela FJ. Comparison
of hilbert transform and wavelet methods for the analysis of neuronal synchrony. J Neurosci
Methods 2001;111:83–98. [PubMed: 11595276]
Levine B, Roehrs T, Stepanski E, Zorick F, Roth T. Fragmenting sleep diminishes its recuperative value.
Sleep 1987;10:590–599. [PubMed: 3432859]
Levine B, Roehrs T, Zorick F, Roth T. Daytime sleepiness in young adults. Sleep 1988;11:39–46.
[PubMed: 3363268]
Linde L, Bergstrom M. The effect of one night without sleep on problem-solving and immediate recall.
Psychol Res 1992;54:127–136. [PubMed: 1620796]
Livingstone MS, Hubel DH. Effects of sleep and arousal on the processing of visual information in the
cat. Nature 1981;291(5816):554–561. [PubMed: 6165893]
Lockley SW, Cronin JW, Evans EE, Cade BE, Lee CJ, Landrigan CP, Rothschild JM, Katz JT, Lilly CM,
Stone PH, Aeschbach D, Czeisler CA. for the Harvard Work Hours, Health and Safety Group. Effect
of reducing interns’ weekly work hours on sleep and attentional failures. N Engl J Med
2004;351:1829–1837. [PubMed: 15509816]
Loeb, M.; Alluisi, E. Theories of vigilance. In: Warm, JS., editor. Sustained attention in human
performance. London: Wiley; 1984. p. 179-205.
Lorenzo I, Ramos J, Arce C, Guevara M, Corsi-Cabrera M. Effect of total sleep deprivation on reaction
time and waking EEG activity in man. Sleep 1995;18:346–354. [PubMed: 7676168]
Lorist M, Snel J, Kok A, Mulder G. Influence of caffeine on selective attention in well-rested and fatigued
subjects. Psychophysiology 1994;31:525–534. [PubMed: 7846213]
Lou J-S, Kearns G, Benice T, Oken B, Sexton G, Nutt J. Levodopa improves physical fatigue in
parkinson’s disease: a double-blind, placebo-controlled, cross-over study. Mov Disord
2003;18:1108–1114. [PubMed: 14534913]
Lowenstein O, Feinberg R, Lowenfeld IE. Pupillary movements during acute and chronic fatigue. Invest
Ophthalmol 1963;2:138–157.
Lu J, Greco MA, Shiromani P, Saper CB. Effect of lesions of the ventrolateral preoptic nucleus on nrem
and rem sleep. J Neurosci 2000;20(10):3830–3842. [PubMed: 10804223]
Lugaresi E. The thalamus and insomnia. Neurology 1992;42(7 Suppl):28–33. [PubMed: 1630636]
Mackworth JF. Performance decrement in vigilance, threshold, and highspeed perceptual motor tasks.
Can J Psychol 1964;18:209–223. [PubMed: 14216122]
Mackworth NH, Kaplan IT, Metlay W. Eye movements during vigilance. Percept Mot Skills
1964;18:397–402. [PubMed: 14166028]

Oken et al. Page 22
Magill RA, Waters WF, Bray GA, Volaufova J, Smith SR, Lieberman HR, McNevin N, Ryan DH. Effects
of tyrosine, phentermine, caffeine d-amphetamine, and placebo on cognitive and motor performance
deficits during sleep deprivation. Nutr Neurosci 2003;6(4):237–246. [PubMed: 12887140]
Makeig S, Inlow M. Lapses in alertness: coherence of fluctuations in performance and EEG spectrum.
Electroencephalogr Clin Neurophysiol 1993;86(1):23–35. [PubMed: 7678388]
Makeig S, Jung TP. Changes in alertness are a principal component of variance in the EEG spectrum.
Neuroreport 1995;7(1):213–216. [PubMed: 8742454]
Makeig S, Jung TP. Tonic, phasic, and transient EEG correlates of auditory awareness in drowsiness.
Brain Res Cogn Brain Res 1996;4(1):15–25. [PubMed: 8813409]
Makeig S, Jung T-P, Sejnowski T. Awareness during drowsiness: dynamics and electrophysiological
correlates. Can J Exp Psychol 2000;54:266–273. [PubMed: 11195717]
Makeig S, Westerfield M, Jung T-P, Enghoff S, Townsend J. Dynamic brain sources of visual evoked
responses. Science 2002;295:690–694. [PubMed: 11809976]
Makeig S, Delorme A, Westerfield M, Jung T-P, Townsend J, Courchesne E, Sejnowski TJ.
Electroencephalographic brain dynamics following manually responded visual targets. PLoS Biol
2004;2(6):e176. [PubMed: 15208723]
Marcus C, Loughlin G. Effects of sleep deprivation on driving safety in housestaff. Sleep 1996;19:763–
766. [PubMed: 9085483]
Martin S, Engleman H, Deary I, Douglas N. The effect of sleep fragmentation on daytime function. Am
J Respir Crit Care Med 1996;153:1328–1332. [PubMed: 8616562]
Matousek M, Petersen I. A method for assessing alertness fluctuations from EEG spectra.
Electroencephalogr Clin Neurophysiol 1983;55:108–113. [PubMed: 6185295]

Mazza S, Pepin JL, Naegele B, Plante J, Deschaux C, Levy P. Most obstructive sleep apnoea patients
exhibit vigilance and attention deficits on an extended battery of tests. Eur Respir J 2005;25(1):75–
80. [PubMed: 15640326]
McCarley RW, Benoit O, Barrionuevo G. Lateral geniculate nucleus unitary discharge in sleep and
waking: state- and rate-specific aspects. J Neurophysiol 1983;50(4):798–818. [PubMed: 6631464]
McCarthy M, Waters W. Decreased attentional responsivity during sleep deprivation: orienting response
latency, amplitude, and habituation. Sleep 1997;20:115–123. [PubMed: 9143071]
McCormick DA, Bal T. Sleep and arousal: thalamocortical mechanisms. Annu Rev Neurosci
1997;20:185–215. [PubMed: 9056712]
McCormick DA, Feeser HR. Functional implications of burst firing and single spike activity in lateral
geniculate relay neurons. Neuroscience 1990;39(1):103–113. [PubMed: 2089273]
McEwen BS. The neurobiology of stress: from serendipity to clinical relevance. Brain Res 2000;886(1–
2):172–189. [PubMed: 11119695]
McGinty D, Szymusiak R. Brain structures and mechanisms involved in the generation of nrem sleep:
focus on the preoptic hypothalamus. Sleep Med Rev 2001;5(4):323–342. [PubMed: 12530996]
McLaren JW, Erie JC, Brubaker RF. Computerized analysis of pupillograms in studies of alertness. Invest
Ophthalmol Vis Sci 1992;33(3):671–676. [PubMed: 1544791]
Merica H, Gaillard J. The EEG of the sleep onset period in insomnia: a discriminant analysis. Physiol
Behav 1992;52(2):199–204. [PubMed: 1523243]
Merriam-Webster [online]. 2005 [cited 2005 August 17]. Available from:
http://www.m-w.com/cgi-bin/dictionary
Mesulam M. Large scale neurocognitive networks and distributed processing for attention, language and
memory. Ann Neurol 1990;19:597–613. [PubMed: 2260847]
Mezzanotte WS, Tangel DJ, White DP. Influence of sleep onset on upper-airway muscle activity in apnea
patients versus normal controls. Am J Respir Crit Care Med 1996;153(6 Pt 1):1880–1887. [PubMed:
8665050]
Mignot E, Lammers GJ, Ripley B, Okun M, Nevsimalova S, Overeem S, Vankova J, Black J, Harsh J,
Bassetti C, Shrader H, Nishino S, et al. The role of cerebrospinal fluid hypocretin measurement in
the diagnosis of narcolepsy and other hypersomnias. Arch Neurol 2002;59(10):1553–1562.
[PubMed: 12374492]

Oken et al. Page 23
Mitler MM, Gujavarty KS, Browman CP. Maintenance of wakefulness test: a polysomnographic
technique for evaluating efficacy in patients with excessive somnolence. Electroencephalogr Clin
Neurophysiol 1982;53:658–661. [PubMed: 6177511]
Mitler M, Carskadon M, Czeisler C, Dement W, Dinges D, Graeber R. Catastrophes, sleep, and public
policy: consensus report. Sleep 1988;11:100–109. [PubMed: 3283909]
Mitler MM, Miller JC, Lipsitz JJ, Walsh JK, Wylie CD. The sleep of long-haul truck drivers. N Engl J
Med 1997;337:755–761. [PubMed: 9287232]
Mizuhara H, Wang L-Q, Kobayashi K, Yamaguchi Y. A long-range cortical network emerging with theta
oscillation in a mental task. Neuroreport 2004;15:1233–1238. [PubMed: 15167540]
Moore S, Bonnet M, Warm J, Kramer M. Estimates of sleep latency in the morning and at sleep onset in
insomic and normal subjects. Sleep Res 1981;10:219.
Morris TL, Miller JC. Electrooculographic and performance indices of fatigue during simulated flight.
Biol Psychol 1996;42(3):343–360. [PubMed: 8652752]
Morris A, So Y, Lee K, Lash A, Becker C. The p300 event-related potential: the effects of sleep
deprivation. J Occup Med 1992;34:1143–1152. [PubMed: 1464782]
Moruzzi G, Magoun HW. Brain stem reticular formation and activation of the EEG. Electroencephalogr
Clin Neurophysiol 1949;1:455–473. [PubMed: 18421835]
Mountcastle VB. Brain mechanisms for directed attention. J R Soc Med 1978;71(1):14–28. [PubMed:
416210]
Mu Q, Nahas Z, Johnson K, Yamanaka K, Mishory A, Koola J, Hill S, Horner MD, Bohning DE, George
MS. Decreased cortical response to verbal working memory following sleep deprivation. Sleep
2005;28:55–67. [PubMed: 15700721]

Naifeh K, Kamiya J. The nature of respiratory changes associated with sleep onset. Sleep 1981;4(1):49–
59. [PubMed: 6785856]
Naitoh P, Johnson LC, Lubin A. Modification of surface negative slow potential (CNV) in the human
brain after total sleep loss. Electroencephalogr Clin Neurophysiol 1971;30:17–22. [PubMed:
4099532]
Naitoh P, Kelly T, Babkoff H. Sleep inertia: best time not to wake up? Chronobiol Int 1993;10:109–118.
[PubMed: 8500187]
Nebes RD, Brady CB. Phasic and tonic alertness in alzheimer’s disease. Cortex 1993;29(1):77–90.
[PubMed: 8472560]
Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E. Hypocretin (orexin) deficiency in human
narcolepsy. Lancet 2000;355(9197):39–40. [PubMed: 10615891]
Nykamp K, Rosenthal L, Folkerts M, Roehrs T, Guido P, Roth T. The effects of rem sleep deprivation
on the level of sleepiness/alertness. Sleep 1998;21:609–614. [PubMed: 9779520]
Ogilvie RD. The process of falling asleep. Sleep Med Rev 2001;5(3):247–270. [PubMed: 12530990]
Ogilvie RD, Wilkinson RT. The detection of sleep onset: behavioral and physiological convergence.
Ogilvie RD, mcDonagh D, Stone S, Wilkinson R. Eye movements and the detection of sleep onset.

Ogilvie RD, Wilkinson R, Allison S. The detection of sleep onset: behavioral, physiological and
subjective convergence. Sleep 1989;12:458–474. [PubMed: 2799219]
Oken, BS. Endogenous event-related potentials. In: Chiappa, KH., editor. Evoked potentials in clinical
medicine. 3rd ed.. Philadelphia: Lipplincott-Raven; 1997. p. 529-564.
Onton J, Delorme A, Makeig S. Frontal midline EEG dynamics during working memory. NeuroImage
1995;27:341–356. [PubMed: 15927487]
Otmani S, Pebayle T, Roge J, Muzet A. Effect of driving duration and partial sleep deprivation on
subsequent alertness and performance of car drivers. Physiol Behav 2005;84(5):715–724. [PubMed:
15885247]
Pace-Schott E, Hobson J. The neurobiology of sleep: genetics, cellular physiology and subcortical
networks. Nat Rev Neurosci 2002;3:591–605. [PubMed: 12154361]
Parasuraman. Memory load event rate control sensitivity decrements in sustained attention. Science
1979;205:924–927. [PubMed: 472714]

Oken et al. Page 24
Parasuraman, R. The attentive brain. Parasuraman, R., editor. Cambridge, MA: The MIT Press; 1998a.
Parasuraman, R.; Warm, JS.; See, JE. Brain systems of vigilance. In: Parasuraman, R., editor. The
attentive brain. Cambridge, MA: The MIT Press; 1998b. p. 221-256.
Penzel T, Petzold J. A new method for the classification of subvigil stages, using the fourier transform,
and its application to sleep apnea. Comput Biol Med 1989;19(1):7–34. [PubMed: 2917463]
Pfurtscheller G, Aranibar A. Event-related cortical desynchronization detected by power measurements
of scalp EEG. Electroencephalogr Clin Neurophysiol 1977;42:817–826. [PubMed: 67933]
Philip P, Stoohs R, Guilleminault C. Sleep fragmentation in normals: a model for sleepiness associated
with the upper airway resistance syndrome. Sleep 1994;17:242–247. [PubMed: 7939124]
Pilcher J, Huffcutt A. Effects of sleep deprivation on performance: a meta-analysis. Sleep 1996;19:318–
326. [PubMed: 8776790]
Pineda JA, Foote SL, Neville HJ. Effects of locus coeruleus lesions on auditory, long-latency, event-
related potentials in monkey. J Neurosci 1989;9:81–93. [PubMed: 2563282]
Pivik R, Busby K. Heart rate associated with sleep onset in preadolescents. J Sleep Res 1996;5:33–36.
[PubMed: 8795799]
Posner M, Petersen S. The attentional system of the human brain. Ann Rev Neurosci 1990;13:25–42.
[PubMed: 2183676]
Ranganath C, Rainer G. Neural mechanisms for detecting and remembering novel events. Nat Rev
Neurosci 2003;4:193–202. [PubMed: 12612632]
Raz A, Deouell L, Bentin S. Is pre-attentive processing compromised by prolonged wakefulness? Effects
of total sleep deprivation on mismatch negativity. Psychophysiology 2001;38:787–795. [PubMed:
11577902]
Rechtschaffen, A.; Kales, A. A manual of standardized terminology, techniques and scoring system for
sleep stages of human subjects. Bethesda: National Institute of Health; 1968.
Reynolds JH, Pasternak T, Desimone R. Attention increases sensitivity of v4 neurons. Neuron
2000;26:703–714. [PubMed: 10896165]
Richardson GS, Wyatt JK, Sullivan JP, Orav EJ, Ward AE, Wolf MA, Czeisler CA. Objective assessment
of sleep and alertness in medical house staff and the impact of protected time for sleep. Sleep
1996;19:718–726. [PubMed: 9122559]
Ritter W, Simson R, Vaughn H, Friedman D. A brain event related to the making of a sensory
discrimination. Science 1979;203:1358–1361. [PubMed: 424760]
Robbins TW. Arousal systems and attentional processes. Biol Psychol 1997;45:57–71. [PubMed:
9083644]
Robbins TW, Everitt BJ. Neurobehavioral mechanisms of reward and motivation. Curr Opin Neurobiol
1996;6:228–236. [PubMed: 8725965]
Rockstroh B, Johnen M, Elbert T, Lutzenberger W, Birbaumer N, Rudolph K, Ostwald J, Schnitzler HU.
The pattern and habituation of the orienting response in man and rats. Intern J Neurosci
1987;37:169–182.
Roehrs T, Timms V, Zwyghuizen-Doorenbos A, Roth T. Sleep extension in sleepy and alert normals.
Sleep 1989;12:449–457. [PubMed: 2799218]

Rosenthal L, Roehrs T, Rosen A, Roth T. Level of sleepiness and total sleep time following various time
in bed conditions. Sleep 1993;16:226–232. [PubMed: 8506455]
Salinsky MC, Oken BS, Binder LM. Assessment of drowsiness in epilepsy patients receiving chronic
antiepileptic drug therapy. Epilepsia 1996;37:181–187. [PubMed: 8635429]
Sangal RB, Sangal JM. Rating scales for inattention and sleepiness are correlated in adults with symptoms
of sleep disordered breathing syndrome, but not in adults with symptoms of attention-deficit/
hyperactivity disorder. Sleep Med 2004;5(2):133–135. [PubMed: 15033132]
Sangal RB, Thomas L, Mitler MM. Maintenance of wakefulness test and multiple sleep latency test.
Measurement of different abilities in patients with sleep disorders. Chest 1992;101(4):898–902.
[see comments]. [PubMed: 1555459]
Santamaria, J.; Chiappa, KH. The EEG of drowsiness. New York: Demos Publications; 1987a.
Santamaria J, Chiappa KH. The EEG of drowsiness in normal adults. J Clin Neurophysiol 1987b;4(4):
327–382. [PubMed: 3316272]

Oken et al. Page 25
Saper C, Chou T, Scammell T. The sleep switch: hypothalamic control of sleep and wakefulness. Trends
Neurosci 2001;24(12):726–731. [PubMed: 11718878]
Schroeder SR, Holland JG. Operant control of eye movements during human vigilance. Science 1968;161
(838):292–293. [PubMed: 5657337]

Schultz W. Getting formal with dopamine and reward. Neuron 2002;36:241–263. [PubMed: 12383780]
Sforza E, Montagna P, Tinuper P, Cortelli P, Avoni P, Ferrillo F, Petersen R, Gambetti P, Lugaresi E.
Sleep–wake cycle abnormalities in fatal familial insomnia. Evidence of the role of the thalamus in
sleep regulation. Electroenceph Clin Neurophysiol 1995;94(6):398–405. [PubMed: 7607093]
Shimazono Y, Ando K, Sakamoto S, Tanaka T, Eguchi T, Nakamura H. Eye movements of waking
subjects with closed eyes. A comparison between normals and chronic schizophrenics. Arch Gen
Psychiatry 1965;13(6):537–543. [PubMed: 5841753]
Siddle DA. Vigilance decrement and speed of habituation of the gsr component of the orienting response.
Br J Psychol 1972;63(2):191–194. [PubMed: 5045587]
Simon CW, Emmons WH. EEG, consciousness, and sleep. Science 1956;124:1066–1069. [PubMed:
13380420]
Smith M, McEvoy L, Gevins A. The impact of moderate sleep loss on neurophysiologic signals during
working-memory task performance. Sleep 2002;25:56–66.
Sokolov, EN. Perception and the conditioned reflex. New York: Macmillan; 1963.
Squires NK, Squires KC, Hillyard SA. Two varieties of long-latency positive waves evoked by
unpredictable auditory stimuli in man. Electroenceph Clin Neurophysiol 1975;38:387–401.
[PubMed: 46819]
Steele M, John O, Watson W, Thomas H, Muelleman R. The occupational risk of motor vehicle collisions
for emergency medicine residents. Acad Emerg Med 1999;6:1050–1053. [PubMed: 10530665]
Stepanski E. The effect of sleep fragmentation on daytime function. Sleep 2002;25:268–276. [PubMed:
12003157]
Steriade M. Coherent oscillations and short-term plasticity in corticothalamic networks. Trends Neurosci
1999;22(8):337–345. [PubMed: 10407416]
Steriade M. Corticothalamic resonance, states of vigilance and mentation. Neuroscience 2000;101(2):
243–276. [PubMed: 11074149]
Steriade M, Oakson G, Ropert N. Firing rates and patterns of midbrain reticular neurons during steady
and transitional states of the sleep waking cycle. Exp Brain Res 1982;46:37–51. [PubMed: 7067790]
Steriade M, McCormick D, Sejnowski T. Thalamocortical oscillations in the sleeping and aroused brain.
Science 1993;262:679–685. [PubMed: 8235588]
Steriade M, Amzica F, Contreras D. Synchronization of fast (30–40 Hz) spontaneous cortical rhythms
during brain activation. J Neurosci 1996;16(1):392–417. [PubMed: 8613806]
Stern JA, Boyer D, Schroeder D. Blink rate: a possible measure of fatigue. Human Factors 1994;36(2):
285–297. [PubMed: 8070793]
Steyvers F, Gaillard A. The effects of sleep-deprivation and incentives on human performance. Psychol
Res 1993;55:64–70. [PubMed: 8480005]
Strauss J, Lewis JL, Klorman R, Peloquin LJ, Perlmutter RA, Salzman LF. Effects of methylphenidate
on young adults’ performance and event-related potentials in a vigilance and a paired-associates
learning test. Psychophysiology 1984;21(6):609–621. [PubMed: 6514938]
Strijkstra AM, Beersma DG, Drayer B, Halbesma N, Daan S. Subjective sleepiness correlates negatively
with global alpha (8–12 Hz) and positively with central frontal theta (4–8 Hz) frequencies in the
human resting awake electroencephalogram. Neurosci Lett 2003;340(1):17–20. [PubMed:
12648748]
Surwillo W, Quilter B. The relation of frequency of spontaneous skin potential responses to vigilance
and to age. Psychophysiology 1965;1(3):272–276. [PubMed: 14265423]
Szymusiak R. Magnocellular nuclei of the basal forebrain: substrates of sleep and arousal regulation.
Sleep 1995;18(6):478–500. [PubMed: 7481420]
Tecce JJ. A CNV. rebound effect. Electroenceph Clin Neurophysiol 1979;46:546–551. [PubMed: 88343]
Torsvall L, Akerstedt T. Sleepiness on the job: continuously measured EEG changes in train drivers.
Electroenceph Clin Neurophysiol 1987;66(6):502–511. [PubMed: 2438115]

Oken et al. Page 26
Torsvall L, Akerstedt T. Disturbed sleep while being on call: an EEG study of ships’ engineers. Sleep
1988a;11:35–38. [PubMed: 3363267]
Torsvall L, Akerstedt T. Extreme sleepiness: quantification of eog and spectral EEG parameters. Int J
Neurosci 1988b;38:435–441. [PubMed: 3372157]

Townsend RE, Johnson LC. Relation of frequency-analyzed EEG to monitoring behavior. Electroenceph
Clin Neurophysiol 1979;47(3):272–279. [PubMed: 90598]
Trinder J, Whitworth F, Kay A, Wilkin P. Respiratory instability during sleep onset. J Appl Physiol
1992;73(6):2462–2469. [PubMed: 1490959]
Valentino RJ, Page M, Van Bockstaele E, Aston-Jones G. Corticotropin-releasing factor innervation of
the locus coeruleus region: distribution of fibers and sources of input. Neuroscience 1992;48(3):
689–705. [PubMed: 1376457]
Valentino DA, Arruda JE, Gold SM. Comparison of qeeg and response accuracy in good vs poorer
performers during a vigilance task. Int J Psychophysiol 1993;15(2):123–133. [PubMed: 8244840]
Valley V, Broughton R. The physiological (EEG) nature of drowsiness and its relation to performance
deficits in narcoleptics. Electroenceph Clin Neurophysiol 1983;55:243–251. [PubMed: 6186455]
Van Den Heuvel C, Noone J, Lushington K, Dawson D. Changes in sleepiness and body temperature
precede nocturnal sleep onset: evidence from a polysomnographic study in young men. J Sleep Res
1998;7(3):159–166. [PubMed: 9785270]
Van Dongen H, Price N, Mullington J, Szuba M, Kapoor S, Dinges D. Caffeine eliminates psychomotor
vigilance deficits from sleep inertia. Sleep 2001;24:813–919. [PubMed: 11683484]
Van Dongen HPA, Maislin G, Mullington JM, Dinges DF. The cumulative cost of additional wakefulness:
dose–response effects on neurobehavioral functions and sleep physiology from chronic sleep
restriction and total sleep deprivation. Sleep 2003;26(2):117–126. [PubMed: 12683469]
Van Dongen HP, Baynard MD, Maislin G, Dinges DF. Systematic interindividual differences in
neurobehavioral impairment from sleep loss: evidence of trait-like differential vulnerability. Sleep
2004;27(3):423–433. [PubMed: 15164894]
Van Orden KF, Jung TP, Makeig S. Combined eye activity measures accurately estimate changes in
sustained visual task performance. Biol Psychol 2000;52(3):221–240. [PubMed: 10725565]
Vanderwolf C, Robinson T. Reticulo-cortical activity and behavior: a critique of the arousal theory and
a new synthesis. Behav Brain Sci 1981;4:459–514.
Varela F, Lachaux J-P, Rodriguez E, Martinerie J. The brainweb: phase synchronization and large scale
integration. Nat Rev Neurosci 2001;2:229–239. [PubMed: 11283746]
Verstraeten E, Cluydts R. Executive control of attention in sleep apnea patients: theoretical concepts and
methodological considerations. Sleep Med Rev 2004;8(4):257–267. [PubMed: 15233954]
Vollestad NK. Measurement of human muscle fatigue. J Neurosci Methods 1997;74:219–227. [PubMed:
9219890]
von Economo C. Sleep as a problem of localization. J Nerv Ment Dis 1930;71(3):249–259.
Webb W, Agnew H. Reaction time and serial response efficiency on arousal from sleep. Percept Mot
Skills 1964;18:783–784. [PubMed: 14172528]
Welch AJ, Richardson PC. Computer sleep stage classification using heart rate data. Electroenceph Clin
Neurophysiol 1973;34(2):145–152. [PubMed: 4119527]
Wesenten N, Belenky G, Kautz M, Thorne D, Reichardt R, Balkin T. Maintining alertness and
performance during sleep deprivation: modafanil versus caffeine. Psychopharmacology
2002;159:238–247. [PubMed: 11862356]
Wilkinson, R. Sleep deprivation. In: Edholm, E.; Bacharach, A., editors. The physiology of human
survival. 1965. p. 399-430.
Williams HL, Tepas DI, Morlock HC Jr. Evoked responses to clicks and electroencephalographic stages
of sleep in man. Science 1962;138:685–686. [PubMed: 14000871]
Yerkes R, Dodson J. The relation of strength of stimulus to rapidity of habit-formation. J Comp Neurol
Psychol 1908;18:459–482.
Yoss RE, Moyer NJ, Hollenhorst RW. Pupil size and spontaneous pupillary waves associated with
alertness, drowsiness and sleep. Neurology 1970;20:545–554. [PubMed: 5463609]

Oken et al. Page 27
Zemaityte D, Varoneckas G. Heart rhythm control during sleep. Psychophysiology 1984;21(3):279–289.

[PubMed: 6739669]

Oken et al. Page 28
Fig. 1.
Error rate and EEG spectral power for a single subject during a 28-min continuous performance
task. The local error rate is plotted to the left of the spectra. Note the relationship between
changes in the EEG spectrum (decreases in alpha frequency and increases in theta frequency
activity) and increasing error rate over time. From Makeig et al. (1993).

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Clin Neurophysiol. 2006 September ; 117(9): 1885–1901. doi:10.1016/j.clinph.2006.01.017.

Vigilance, alertness, or sustained attention: physiological basis

B.S. Okena,b,*, M.C. Salinskya, and S.M. Elsasa

Jackson Park Road, Portland, OR 97239, USA

2. Underlying mechanisms and physiology

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

hypothalamo–pituitary–adrenal axis, and limbic system (including amygdala and nucleus

motivation and cognitive processing.

2.1. Sleep–wake systems

In addition to systems to promote wakefulness there is at least one hypnogenic or sleep-

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

2.2. Neurotransmitter systems

2.2.1. Locus coeruleus–norepinephrine—The Locus coeruleus–norepinephrine (LC–

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

2.2.2. Cholinergic systems—Brain-stem and basal forebrain cholinergic activity are

2.3. Other factors impacting sustained attention

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

to be affected by post-traumatic stress disorder which is associated with hypervigilance,

2.3.3. Cognitive aspects and habituation—Vigilance is affected by some cognitive

2.4. Physiologic correlates

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

alpha, are attenuated. This was initially described as event-related desynchronization

Using magneto-EEG to investigate the attentional blink phenomenon, neuronal synchrony in

3. Conditions associated with changes in alertness and sustained attention

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

to conventional EEG changes, there is decreased amplitude of long-latency evoked potentials

3.1.2. Sleep–wake transition—The transition from sleep to awake is similar

3.1.3. Quantitative EEG measures—Using more quantitative measures for alertness,

3.1.3.1. EEG-performance relationship: There is a very large literature concerning the

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

3.2. Sleep loss

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

(Carskadon, 1981; Dinges et al., 1997; Van Dongen, 2003).

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

3.2.2. Electrophysiological measures

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

3.2.2.2. Event related potentials

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

3.2.3. Sleep deprivation summary—In summary, there is extensive behavioral and

with stimulus discrimination (N2, N170, P3).

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

1998;95(1):322–327. [PubMed: 9419374]

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

maintenance of wakefulness test (MWT). Electroencephalogr Clin Neurophysiol 1997;103(5):554–

of state instability. Arch Ital Biol 2001;139:253–267. [PubMed: 11330205]

Friedman W. Resident duty hours in neurosurgery. Neurosurgery 2004;54:925–931. [PubMed:

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

Hömberg V, Grnewald G, Grnewald-Zuberbier E. The variation of p300 amplitude in a money winning

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

Kaiser J, Lutzenberger W. Human gamma-band activity: a window to cognitive processing. Neuroreport

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

Electroencephalogr Clin Neurophysiol 1983;55:108–113. [PubMed: 6185295]

Clin Neurophysiol. Author manuscript; available in PMC 2010 May 6.

2005;28:55–67. [PubMed: 15700721]