3 - ENABLING TECHNOLOGY
Functional Neuroimaging of Sleep and Wake
Although the physiological
and adaptive functions of sleep remain to be clarified, it is
clear that sleep and wakefulness are neurologically mediated.
Sleep researchers have employed behavioral observations, clinicopathologic
observations, correlative studies with polysomnographic measures,
and extrapolations based on invasive research in non-human subjects
in order to characterize and understand the brain processes
mediating and constituting sleep and wakefulness. Each of these
approaches continue to yield new knowledge about sleep and the
brain, and each provides a unique view, or "level of analysis"
of sleep and brain functioning ranging from the behavior of
single neurons to the behavior of the entire organism. The ultimate
result of this multifaceted approach is likely to be a comprehensive
and coherent understanding of sleep.
imaging techniques (such as positron emission tomography (PET),
functional magnetic resonance imaging (fMRI), Magnetic Resonance
Spectroscopy (MRS), single photon emission computed tomography
(SPECT), magnetoelectroencephalography (MEG), and near-infrared
optical imaging (NIR) have enabled new and unique analyses in
the study of sleep and waking. These techniques allow measurement
of metabolic and neurochemical activity throughout the brain,
and can discern dynamic patterns of regional cerebral activity
during various brain states including stages of sleep and levels
of alertness during wakefulness or during functional challenge).
Furthermore, these techniques are likely to enhance identification
of both normal and abnormal sleep/wake processes.
In The Last 5 Years
- Functional neuroimaging
techniques (primarily PET) reveal that NREM sleep is associated
with deactivation of centrencephalic regions (brainstem, thalamus,
basal ganglia) and multimodal association cortices (e.g., prefrontal
and superior temporal/inferior parietal regions). REM sleep
is characterized by reactivation of all centrencephalic regions
deactivated during NREM sleep except the multimodal association
areas. Thus, deactivation of the multimodal association areas
has been shown to be a defining characteristic of sleep.
- PET studies during
sleep-deprived wakefulness reveal regional cerebral deactivations
that are especially prominent in prefrontal and inferior parietal/superior
temporal cortices, and in the thalamus. These patterns are similar
to that found during NREM sleep, but the deactivations are of
lesser magnitude than during NREM sleep). This pattern is consistent
with, and helps explain, the nature of cognitive performance
deficits that occur during sleep loss. Considered together with
results of sleep studies, this pattern suggests that NREM sleep
initiation and sleep-deprived wakefulness in healthy individuals
are manifestations of related neurobiological processes.
- Relative activation/deactivation
patterns revealed by fMRI techniques during performance of cognitive
tasks suggest that maintenance of performance following sleep
loss may be a function of the extent to which other cortical
brain regions can be recruited for task performance in the sleep-deprived
state. This is one of a number of possible ways that individual
differences may occur in the ability to maintain alertness and
performance following sleep loss.
- PET, SPECT and
fMRI studies reveal that a subset of depressed patients show
initially elevated activation in anterior cingulate and medial
orbital cortices. In these patients, sleep deprivation reduces
this regional hyper-activation, and improvements in mood are
a function of the extent to which this activity is reduced.
These studies suggest possible mechanisms by which antidepressant
drugs may exert their effects.
- PET scans reveal
that the midbrain reticular activating system remains relatively
active during stage 2 sleep-a finding that may account for the
relatively heightened arousability that characterizes this stage
- PET scans taken
at 5 vs. 20 minutes after awakening suggest that re-emergence
of conscious awareness upon awakening occurs as a function of
centrencephalic reactivation, and reestablishment of a specific
pattern of functional interconnectivity between brain regions.
These data also suggest that restoration of alertness (e.g.,
dissipation of sleep inertia effects) occurs as a function of
reactivation and reestablishment of functional interconnectivity
patterns involving prefrontal cortices. These findings could
constitute an important first step toward specification of the
physiological basis of post-sleep waking cognitive capability.
- Perform neuroimaging
studies that measure absolute as well as relative changes in
brain metabolic activity and neurotransmitter levels. Such studies
are needed to (1) determine the effects of sensory and cognitive
demands on subsequent levels and patterns of regional brain
activity during both sleep and wakefulness and as a function
of state changes, and (2) to establish the functional neuroanatomy
of sleep, wakefulness, alertness, and cognitive capability.
- Apply the enhanced
capabilities afforded by improved functional neuroimaging, including
greater temporal and spatial resolution, to study sleep and
sleep disorders. These applications will help to determine the
physiological correlates of phasic events like eye movements
during REM, sleep-dependent changes in activity levels of specific
thalamic nuclei, and brain changes subserving microsleeps and
lapses of attention.
- Utilize functional
neuroimaging techniques to determine the functional neuroanatomy
of REM sleep, NREM sleep, and waking in patients in sleep disorders
such as Narcolepsy, REM behavior disorder, and Restless Legs
Syndrome. Such studies will yield insight into the pathophysiology
of these disorders. Similar studies in patients with other disorders
known to impact sleep processes (e.g., depression, chronic pain
conditions) will yield insight into the pathophysiology of these
- The effects of
sleep and alertness-promoting pharmacological agents on patterns
of regional brain activation/deactivation and on occupancy/activation
at specific receptor sites should be determined. Such studies
will elucidate the mechanisms by which these agents impact sleep/wake
processes, and will facilitate the development of new agents
that might more specifically target sleep/wake-relevant sites
- Develop new approaches
to obtain polysomnographic measures and other physiological
signals during MRI scanning to facilitate the study of sleep
and alertness unaffected by electromagnetic interference from
the MRI scanner.