Sleep and its disorders are complex, and their mechanisms remain only partially understood. However, neuroimaging studies on specific aspects of several sleep disorders have shown that functional as well as structural brain alterations can be identified. Structural and functional alterations can inform us of the neural mechanisms underlying the nighttime and daytime manifestations of sleep disorders, including their impact on cognitive function. Therefore, neuroimaging may assist us in uncovering the physiological underpinnings of these conditions and the targets for the development or monitoring of sleep-related interventions. There is a wide range of sleep disorders, and the following sleep disorders are discussed in this article: insomnia, narcolepsy and idiopathic hypersomnia, REM sleep behavior disorder, and obstructive sleep apnea.
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In insomnia, a variety of cognitive and emotional tasks have been used to evaluate functional brain alterations. They generally point to a hyperactivation in response to sleep-related and negative emotional stimuli and a hypoactivation in response to other types of stimuli, such as tasks involving executive control. In contrast, structural brain alterations are inconsistent, perhaps reflecting the complexity and heterogeneity of insomnia and suggesting that sleep-related symptoms in insomnia are reflected in functional rather than structural brain alterations.
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In narcolepsy with cataplexy, structural alterations, such as smaller gray matter volume and altered white matter integrity, are widespread and encompass the hypothalamus and its projections, which is in line with the evidence for loss of hypocretin neurons in the hypothalamus. On the other hand, functional alterations are observed in the hypothalamus, which shows altered activation and regional blood flow during both resting wakefulness and while performing cognitive tasks, such as emotion regulation during positive emotions or cataplexy attacks.
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In REM sleep behavior disorder, functional alterations are widespread across the cortex and involve the limbic network, pons, and thalamus. Specifically, the basal ganglia and sensorimotor network show altered functional connectivity, which might be a predictor of disease progression from REM sleep behavior disorder to Parkinson disease.
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In obstructive sleep apnea, cognitive deficits might stem from lower resting state activity and functional connectivity in the frontoparietal, sensorimotor, and salience networks, which are involved in numerous cognitive processes. However, the pattern of structural alterations is less consistent. Both structural and functional alterations may be partially reversible with continuous positive airway pressure treatment.
Historical note and terminology
Important advances in the understanding of sleep and its disorders have been made using neuroimaging techniques, such as magnetic resonance imaging (MRI), positron emission tomography (PET), or single-photon emission computed tomography (SPECT), as they bring complementary information to electroencephalography (EEG). The understanding of sleep physiology and sleep disorders may, therefore, be improved by investigating structural and functional brain alterations during resting wakefulness, sleep, or while performing a task using these neuroimaging techniques.
MRI is used in clinical practice to investigate brain anatomy, but structural MRI can also provide measures of cortical thickness, regional gray or white matter volume, white matter integrity, and structural connectivity by looking at how water molecules diffuse in the brain. Functional MRI (fMRI) measures changes in cerebral blood flow through a blood-oxygen-level-dependent contrast. Regional brain activity is indirectly measured by measuring the increase of oxygen consumption and, therefore, blood flow resulting from neuronal activity. fMRI can also be used to assess brain activity patterns and functional connectivity. Brain activity can be measured when subjects perform a cognitive task, during sleep, or during resting wakefulness (ie, in the absence of any particular task or sleep). Functional connectivity looks at coactivated brain regions, ie, how different brain regions or networks may communicate with each other. Finally, with magnetic resonance spectroscopy (MRS), one can measure metabolites or neurotransmitter concentration in a specific brain region. Metabolite levels that can be measured include gamma-aminobutyric acid (GABA) and glutamate to assess excitatory and inhibitory neurotransmission. Other molecules can be measured and are used as markers of neuronal or glial integrity, such as N-acetylaspartate, choline, and creatine. In most cases, metabolite levels are measured relative to another metabolite as it is difficult to get quantitative measures.
There are 2 main types of nuclear imaging techniques. The first type is positron emission tomography (PET) imaging and involves injecting a radioactive tracer into the bloodstream, which is detectable within the brain. Depending on the tracer, it is possible to measure the density of neurotransmitter receptors or the regional brain metabolic rate. For example, [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) provides a measurement of regional glucose metabolism within the brain over a short timespan (eg, 2030 min). The second type is single-photon emission computed tomography (SPECT), a technique that also utilizes the injection of a tracer into the bloodstream and can be used to quantify regional cerebral perfusion (blood flow, rCBF) or neurotransmission (depending on the tracer used) in the brain.