Neuroimaging of sleep disorders

Sleep Disorders

Updated 11.19.2023
Released 09.19.2021
Expires For CME 11.19.2026

Neuroimaging of sleep disorders

Authors: Florence Pomares PhD, Nathan Cross PhD, Aurore A Perrault PhD, Thien Thanh Dang-Vu MD PhD FAASM

See Contributor Disclosures

Editor: Antonio Culebras MD FAAN FAHA FAASM

Neuroimaging of sleep disorders

In This Article

Quick Link

Introduction

Overview

Sleep and its disorders are complex, and their mechanisms remain only partially understood. However, neuroimaging studies investigating 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.

Key points

	• 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.
	• 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.
	• 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.
	• 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 metabolites are difficult to quantify individually.

There are two 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, 20–30 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.

Description

Insomnia

	• In insomnia, brain anatomy alterations in the frontoparietal network have been reported but are not consistent across studies, perhaps reflecting the complexity and heterogeneity of insomnia disorder and suggesting that sleep-related symptoms in insomnia are reflected in functional rather than structural brain alterations.
	• Insomnia is characterized by 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.
	• Brain activity and connectivity during resting wakefulness is altered in insomnia, particularly within the default mode and salience networks and between the limbic network and other brain regions. These alterations may contribute to the state of hyperarousal and emotional dysregulation that are present in insomnia.
	• The overall activity decrease in the default mode network in the transition from wakefulness to sleep is less pronounced in insomnia and might reflect heightened arousal.

Definition of insomnia. Insomnia is characterized by difficulties falling asleep and maintaining sleep as well as waking up earlier than desired. It is associated with daytime function impairments, such as fatigue and reported cognitive impairments. The distinguishing features of insomnia have been associated with functional alterations that are, for the most part, in line with the hyperarousal theory of insomnia, which postulates that heightened physiological, cognitive, or emotional arousal observed in insomnia is the result of excessive central nervous system arousal that prevents and disturbs sleep.

Functional brain alterations during cognitive tasks in insomnia. Various cognitive and emotional tasks have been used to evaluate functional brain alterations in insomnia and 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 (45; 47; 55; 73; 85).

The relationship between emotion and hyperarousal has been investigated in several fMRI studies. In a study, greater activation in response to emotional stimuli was present in the amygdala in individuals with insomnia when trying to reinterpret the meaning of negative pictures (23). However, this hyperarousal might be specific to sleep and insomnia as only emotionally arousing stimuli that were related to sleep elicited greater amygdala activation in an emotional reactivity task in individuals with insomnia (05). In addition, the habituation to emotional images that was observed in good sleepers over successive trials was absent in individuals with insomnia (05).

The impairment of daytime functioning is a key feature of insomnia and mainly affects subjective cognitive functioning. Despite inconsistent evidence for objective cognitive impairments, brain cognitive processing as shown by fMRI seems to be altered. Individuals with insomnia had reduced activation of the left medial and inferior frontal gyri during a verbal fluency task involving the executive control network, without showing poorer performance (03). During a working memory task, lower activation in the frontal gyrus and motor and cingulate cortices was observed in individuals with insomnia; they also failed to deactivate the default mode network (21).

Functional brain alterations during resting wakefulness in insomnia. The growing literature on resting wakefulness in insomnia shows an altered brain activity and connectivity, particularly within the default mode and the salience networks and between the limbic network and other brain regions, which are thought to contribute to hyperarousal, emotional regulation, and cognitive alterations that are present in insomnia. Resting state fMRI functional connectivity was found to be lower in the salience and executive control networks and higher in the sensorimotor network (45). In the salience network, the activation of which is associated with negative internal and external stimuli, functional connectivity was associated with negative effect in individuals with insomnia (15; 73). In the limbic network, functional connectivity was decreased between the thalamus and left amygdala, parahippocampal gyrus, putamen, pallidum, and hippocampus (85) as well as between the amygdala and the insula, striatum, and thalamus in individuals with insomnia (37). The latter study also found increased connectivity between the amygdala and the premotor and sensorimotor cortices, which was associated with decreased sleep quality. Altered functional connectivity within the limbic network may be reflective of altered emotional processing in insomnia, and the increased functional connectivity between the amygdala and sensorimotor cortices may support a model of excessive hyperarousal. Additionally, altered functional connectivity between the locus coeruleus, which is involved in the transition between sleep and wake, and other brain networks was associated with poorer sleep quality and greater insomnia symptoms (26; 52).

In the default mode network, a large study from the UK Biobank reported an association between frequent insomnia symptoms (n = 9210) and increased connectivity within the default mode network (33). In addition, an increased negative connectivity between the default mode network and the frontoparietal network, and decreased connectivity between the salience network and a node of the default mode network, were reported. However, inconsistent alterations of functional connectivity and regional brain activity in the cingulate cortex, left insula, left cuneus, and left fusiform gyrus were also observed in smaller studies. Indeed, some studies showed increased connectivity and activation in the default mode network, whereas other showed decreased activity (45). Altered functional connectivity in the default mode network was often associated with subjective sleep disturbances. Additionally, decreased functional connectivity between the medial prefrontal cortex and middle temporal lobe and between the left temporal lobe and left inferior parietal cortex was found in individuals with insomnia (60). Because these regions play an important role in cognitive functioning and sleep physiology, these findings suggest that decreased connectivity may underlie the alteration in cognitive functioning, whereas increased activity at rest might reflect a hyperarousal state in individuals with insomnia. The reduction in brain activation during resting wakefulness has been confirmed using FDG-PET, showing an overall reduction in glucose metabolism in individuals with insomnia. More specifically, an altered engagement of the limbic, default mode, and executive control networks might be reflected by lower middle frontal, fusiform, lingual gyri, precuneus/posterior cingulate, and frontoparietal cortex glucose metabolism in insomnia (46).

Functional brain alterations during sleep and sleep-wake transitions in insomnia. Significant brain activity changes occur during sleep: the overall level of activity decreases in the default mode network, and there is a disconnection (functional connectivity decrease) between its posterior and anterior parts. More specifically, the posterior cingulate cortex and inferior parietal lobe disconnect from the medial prefrontal cortex and anterior cingulate cortex during sleep (35). This disconnection becomes more pronounced as sleep deepens and reaches its lowest level during slow-wave sleep. In individuals with insomnia, this overall activity decrease that happens during sleep seems less pronounced as the decline in regional brain glucose metabolism from wakefulness to sleep is smaller in the medial prefrontal cortex, anterior cingulate, insula, thalamus, hippocampus, amygdala, hypothalamus, and brainstem (61). This was confirmed by another FDG-PET study in a larger sample of individuals showing a smaller decline in brain glucose metabolism during NREM sleep in the default mode network (46). Alterations in other networks are present during sleep in individuals with insomnia as fMRI functional connectivity between the thalamus and left amygdala, parahippocampal gyrus, putamen, pallidum, and hippocampus was decreased across all threec NREM sleep stages.

Summary findings on insomnia

(A) Summary of findings from fMRI studies in insomnia. Overall, there is an increased activation in response to sleep-related and emotional stimuli in the left temporal (including amygdala) and occipital lobes and right frontal...

Structural brain alterations in insomnia. Brain anatomy alterations are inconsistent in individuals with insomnia, potentially because insomnia is a complex and heterogeneous disorder. The discrepancy of results as well as the lack of large sample data make it difficult to draw a clear picture of structural alterations in insomnia and suggest that sleep-related symptoms in insomnia are reflected in functional brain alterations rather than structural brain alterations. A large sample study of 1053 patients with major depressive disorder from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) major depressive disorder consortium showed that insomnia severity was specifically related to smaller cortical surface area in the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus and was independent of major depressive disorder (51). In addition, cortical thinning was found in the anterior cingulate cortex, precentral cortex, and lateral prefrontal cortex in individuals with insomnia disorder (76). However, a subsequent study from the ENIGMA-Sleep consortium did not report any insomnia-specific brain alterations or any significant associations between insomnia symptoms and cortical or subcortical volumes (82).

Previous smaller sample studies had inconsistent findings regarding gray matter volume. Hippocampal gray matter volume was found to be reduced in individuals with insomnia in one study, but this finding was not replicated in other studies. The prefrontal regions (orbitofrontal and dorsolateral prefrontal cortex) were found to be smaller in individuals with insomnia in two studies, but this was not replicated in a latter study. Increased anterior cingulate cortex gray matter volume was found to be associated with increased insomnia severity in individuals with insomnia, but this was not replicated in a larger study.

Fewer studies have examined white matter alterations. Overall, white matter integrity was affected in frontostriatal, frontothalamic, and cortico-cortical networks as well as within the limbic network (mostly shown by reductions in fractional anisotropy or less restricted water diffusion) in individuals with insomnia (59). Lower tract strength, as a marker of poorer white matter integrity, was observed within the limbic network and was negatively correlated with sleep quality in individuals with insomnia (14), showing the importance of emotion regulation in insomnia.

Brain metabolite alterations in insomnia. In terms of neurochemistry, the main metabolite that has been investigated in insomnia is GABA, which is involved in sleep-wake regulation as demonstrated by the use of benzodiazepines (positive allosteric modulators of the GABAA receptor) for the short-term treatment of insomnia. Individuals with insomnia may present an overall reduced inhibitory tone as lower GABA levels have been found in the anterior cingulate and in parieto-occipital cortices. However, higher GABA levels have been found in the occipital cortex (45). Only a handful of studies have investigated other metabolite levels, without consistent results. Phosphocreatine was decreased in individuals with insomnia, suggesting altered cortical energetic demands (30). Aspartate, glutamine, and creatine were decreased in the lateral occipital cortex in individuals with insomnia and short sleep duration (57). Glutamate, an excitatory neurotransmitter, was increased in the parieto-occipital cortex and was associated with insomnia symptoms in patients with posttraumatic stress disorder (45).

Narcolepsy and idiopathic hypersomnia

	• 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.
	• Functional alterations in narcolepsy with cataplexy 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.
	• Idiopathic hypersomnia does not show similar structural alterations as compared to narcolepsy with cataplexy but seems to present a disruption of the default mode network, both at the structural level and at the level of functional connections within regions of the default mode network.

Definition of narcolepsy and idiopathic hypersomnia. Narcolepsy is characterized by excessive daytime sleepiness and abnormalities in REM sleep. Narcolepsy is categorized into two types: narcolepsy with cataplexy (type 1) and narcolepsy without cataplexy (type 2). Narcolepsy with cataplexy is associated with a deficiency in the hypothalamic neuropeptide orexin-A (hypocretin-1), which is involved in the abnormal sleep-wake patterns and cataplexy that are characteristic of narcolepsy. Idiopathic hypersomnia is primarily characterized by excessive daytime sleepiness, together with an often-prolonged total sleep time and difficulties waking up (sleep drunkenness), for which the pathophysiological mechanisms remain unclear. Individuals suffering from idiopathic hypersomnia do not present cataplexy, rapid REM sleep onset (at the multiple sleep latency test), or any consistent hypocretin-1 deficiency.

Functional brain alterations during cognitive tasks in narcolepsy. Based on clinical observations that cataplectic episodes in narcolepsy can be triggered by positive emotions, brain processing involved in emotion and reward have been studied (16). Two fMRI studies used humorous images to study emotional processing and showed alterations in the amygdala and hypocretin system. The first study found reduced hypothalamic activity and increased amygdala activity (74). The second study found enhanced activity in the hypothalamus and emotional network (67). Reward processing was altered in individuals with narcolepsy as they failed to show functional connectivity between the amygdala and medial prefrontal cortex (65). The investigation of other tasks, such as attention or working memory, suggest that narcolepsy is characterized by an imbalance of cognitive resources allocation in favor of monitoring and maintaining attention (27).

Functional brain alterations during resting wakefulness in narcolepsy. Investigation of resting wakefulness in narcolepsy suggests decreased activity in regions that are important targets of hypocretinergic projections (16). An example is decreased regional cerebral blood flow in the brainstem in individuals with narcolepsy (56). Another study found decreased perfusion in the hypothalamus, caudate nuclei, thalamus, cingulate gyrus, and frontoparietal cortex in individuals with narcolepsy with cataplexy (42). However, there have been inconsistent findings regarding glucose metabolism: a first study found hypometabolism in the bilateral hypothalami, thalamus, and frontal-parietal cortex (44) in individuals with narcolepsy, whereas a second study only found hypermetabolism in the cingulate and visual association cortices (19). Similarly, functional connectivity changes have been found in narcolepsy type 1. Increased functional connectivity was found in the left middle occipital gyrus, right inferior occipital gyrus, and lingual gyrus and between the amygdala and the inferior frontal gyrus, claustrum, insula, and putamen. In contrast, decreased functional connectivity was found in the posterior lobe of the cerebellum, left inferior temporal gyrus, and left dorsolateral superior frontal gyrus and between the lateral hypothalamus and the left superior parietal lobule, the hippocampus, and the parahippocampal gyrus, as well as between the amygdala and the post-central gyrus and several occipital regions (07). In addition, a new imaging technique investigating brain pulsation showed altered CSF dynamics in narcolepsy type 1, suggesting altered glymphatic process (41).

Functional brain alterations during sleep in narcolepsy. Findings during REM sleep are inconsistent: some studies report increased activity or an absence of decreased activity that is supposed to occur during sleep (16). A later study found decreased activity in the hypothalamus, caudate nuclei, thalamus, cingulate gyrus, and frontoparietal cortices in narcolepsy with cataplexy (42).

Summary findings on narcolepsy

(A) Summary of findings from fMRI studies in narcolepsy. During winning on a gambling task, activity is reduced in the bilateral nucleus accumbens and the ventromedial prefrontal cortex, and activity is increased in the putamen...

Functional brain alterations during cataplexy in narcolepsy. Because it is difficult to capture cataplectic episodes, only case studies have reported such results, and they show inconsistent findings. Hyperperfusion has been found in limbic areas (including the amygdala and orbitofrontal and anterior cingulate cortices), the thalamus, basal ganglia, brainstem, and parietal cortices (34), whereas hypoperfusion has been found in the prefrontal and occipital cortices (34) and precentral and primary somatosensory cortex (19). The latter observation was supported by an fMRI study that showed marked hypoactivation of the hypothalamus during a cataplectic attack (67).

Functional brain alterations in idiopathic hypersomnia. Only two neuroimaging studies have investigated functional alterations in idiopathic hypersomnia. Although these findings require replication, they suggest functional alterations in brain areas involved in the modulation of vigilance states rather than a loss of hypothalamic orexin neurons. One study found that glucose metabolism was increased in the insula, anterior and middle cingulate cortex, and caudate nucleus (20). Another study showed that regional cerebral blood flow was lower in the medial prefrontal cortex as well as in the posterior cingulate cortex, putamen, and cerebellum in individuals with idiopathic hypersomnia (10). Using fMRI, the same group showed lower functional connectivity within the anterior part of the default mode network (ie, medial prefrontal cortex), which was also associated with sleepiness (64).

Structural brain alterations in narcolepsy. Early structural studies of narcolepsy focused on the pontine tegmentum region in the brainstem as this structure controls the transition between vigilance states, but they found inconsistent results that may be due to heterogeneity in patient characteristics or neuroimaging techniques. Later, in line with evidence suggestive of a hypocretin deficiency, several studies investigated gray matter volume of the hypothalamus. Meta-analyses of those studies have shown inconsistent alterations of thalamic and hypothalamic structures in narcolepsy (28). However, consistent gray matter volume decreases in frontotemporal regions, which might be associated with cognitive complaints of memory and attention, have been observed in narcolepsy with cataplexy. Additionally, alterations in white matter integrity have been found in the hypothalamus-thalamus-orbitofrontal pathway and in the brainstem as well as in the inferior fronto-occipital fasciculus. However, no studies have specifically investigated structural brain alterations in narcolepsy without cataplexy.

Structural brain alterations in idiopathic hypersomnia. Fewer studies have investigated structural brain alterations in idiopathic hypersomnia, and those few reports show no global gray or white matter volume alterations. However, regional brain alterations have been found. Cortical thickness and gray matter volume are larger in the posterior default mode network and in the middle occipital gyrus in individuals with idiopathic hypersomnia. More specifically, the volume of the precuneus was positively associated with greater subjective daytime sleepiness (64).

Brain metabolite alterations in narcolepsy. The investigation of brain metabolite levels in narcolepsy suggests decreased N-acetylaspartate/creatine levels in the hypothalamic region, which is consistent with evidence that hypocretinergic neurons are selectively damaged in narcolepsy (77). However, the thalamus and parieto-occipital cortex, which are also innervated by those neurons, did not reveal any alterations in N-acetylaspartate/creatine levels (78). Finally, absolute GABA concentrations were found to be higher in the medial prefrontal cortex in individuals with narcolepsy, and this was positively associated with nocturnal sleep quality (49).

REM sleep behavior disorder

	• Because of the link between REM sleep behavior disorder and Parkinson disease, structural alterations were primarily investigated in the pons and midbrain as well as in the basal ganglia, all of which involve dopamine transmission. However, structural alterations in REM sleep behavior disorder also encompass temporal, frontal, and parietal cortices.
	• Functional alterations are widespread across the cortex and involve the limbic network, sensorimotor network, pons, and thalamus. More specifically, alteration of functional connectivity within the basal ganglia may be an important marker of basal ganglia network dysfunction.

Definition of REM sleep behavior disorder. REM sleep behavior disorder is a disorder characterized by the loss of muscle atonia during REM sleep, which leads to dream enactment that often results in dramatic movements, such as punching, flailing, or jumping out of the bed, as well as injuries and problems with the bed partner. There is increasing evidence that REM sleep behavior disorder is associated with the alpha-synucleinopathies, such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy; REM sleep behavior disorder is considered a risk factor for alpha-synucleinopathies (40).

Functional brain alterations in REM sleep behavior disorder. Decreased perfusion has been found in the frontal and temporoparietal cortices of individuals with REM sleep behavior disorder; decreased cerebral blood flow has been found in the parietal and occipital cortices as well as in the cerebellum and limbic network (16). Increased perfusion has been observed in the pons, putamen, and hippocampus. The hyperperfusion within the hippocampus predicted the development of dementia with Lewy bodies or Parkinson disease 3 years later, and this occurred in half of the patients (18). REM sleep behavior disorder, a risk factor for alpha-synucleinopathies (40), suggests a dysfunction in dopaminergic transmission, which might play a role in the process leading to neurodegeneration. In addition, decreased glymphatic system flow was associated with increased conversion risk to alpha-synucleinopathies (04). A few neuroimaging studies investigated the dopaminergic system and showed greater dopamine transporter density in individuals with REM sleep behavior disorder, whereas other studies showed no difference or lower dopamine transporter density (16). Longitudinal studies have shown that individuals who developed a neurodegenerative disorder had lower dopamine transporter at baseline (38).

In addition, functional connectivity is altered in the basal ganglia network (68) and in the motor cortex and sublaterodorsal tegmental nucleus (24) in individuals with REM sleep behavior disorder. Lower within-network functional connectivity has been identified between the striatal and prefrontal regions, within the executive control network, between the midbrain and pallidum, within the basal ganglia network, and between motor and somatosensory regions as well as within the sensorimotor network (81). Finally, global basal ganglia resting state connectivity in REM sleep behavior disorder was similar to individuals with Parkinson disease, suggesting that activity within the basal ganglia network may be a marker of basal ganglia dysfunction (68).

Summary findings on REM sleep behavior disorder

Summary of findings from PET and SPECT studies in REM sleep behavior disorder. During episodes of REM behavior disorder, perfusion is increased within the supplementary motor cortex. At wakefulness, perfusion is decreased in th...

Structural brain alterations in REM sleep behavior disorder. REM sleep behavior disorder is characterized by smaller gray matter volume in the thalamus; pontomesencephalic tegmentum; and temporal, frontal, and parietal cortices (24). More severe reductions in volume have been found in Parkinson disease with associated REM sleep behavior disorder (50). Only a couple of studies found increased volume in the caudate nucleus (32). This lower volume in the pontomesencephalic tegmentum is of importance because it contains cholinergic, GABAergic, and glutamatergic neurons implicated in the promotion of REM sleep and muscle atonia (11). Idiopathic REM sleep behavior disorder has also been associated with higher perivascular space burden in the centrum semiovale, basal ganglia, substantia nigra, and brainstem compared to individuals with Parkinson disease, which correlates with REM sleep behavior disorder symptom severity (75). White matter alterations such as higher fractional anisotropy, a marker of more restricted water diffusion, have been found in the pons (80) and other regions known to be involved in REM sleep regulation, such as the pontine region, (72), cerebellar peduncles, and brainstem (32).

Brain metabolite alterations in REM sleep behavior disorder. REM sleep behavior disorder does not seem to involve detectable metabolite alterations in mesopontine regions. Only one case study revealed an increased choline/creatine ratio in the brainstem (58); others failed to replicate these findings (39).

Obstructive sleep apnea

	• Cognitive deficits observed in obstructive sleep apnea might be explained by lower resting state activity and functional connectivity in the frontoparietal, sensorimotor, and salience networks, which are involved in numerous cognitive processes.
	• In contrast, the pattern of structural alterations in obstructive sleep apnea is less consistent. Gray matter atrophy has been observed in the frontal and parietal cortex, temporal lobe, anterior cingulate, thalamus, hippocampus, and cerebellum. White matter alterations encompass the corpus callosum, sensorimotor cingulate cortex, corticospinal tract, insular cortex, basal ganglia, and limbic network.
	• Functional and structural changes may be partially reversible with continuous positive airway pressure treatment.

Definition of obstructive sleep apnea. Obstructive sleep apnea is characterized by recurrent episodes of partial or complete occlusion of the upper airway during sleep, which impedes breathing despite continued inspiratory efforts. The repetitive obstructive events that occur during sleep in obstructive sleep apnea result in variable changes in blood gas concentrations, which lead to hypoxemia (low blood oxygen) and hypercapnia (high blood carbon dioxide). Due to the body’s attempts to regain airflow, the apneic events are strongly correlated with arousals from sleep, leading to significant sleep fragmentation and a reduction in deeper sleep stages. It is well established that obstructive sleep apnea is associated with impairments in cognitive function, particularly in vigilance, attention, memory, and executive function domains. Importantly, obstructive sleep apnea can be controlled with treatments such as continuous positive airway pressure, which serves to maintain airway patency and prevent obstructions.

Functional brain alterations during cognitive tasks in obstructive sleep apnea. Because obstructive sleep apnea is associated with cognitive deficits, functional alterations are more easily detected while performing a cognitive task. A multimodal meta-analysis showed lower activation during various cognitive tasks in individuals with obstructive sleep apnea, specifically in the dorsolateral prefrontal and orbitofrontal cortices; higher activation was found in the insula, anterior cingulate cortex, amygdala, and hippocampus (36). This finding was based on small sample studies investigating different cognitive domains in which working memory, executive functioning, and attention performance were poorer in individuals with obstructive sleep apnea. Lower resting state functional connectivity in the sensorimotor network, salience (insula) network, and frontoparietal network and altered within-network coherence might explain the impaired cognitive and motor performance observed in individuals with obstructive sleep apnea (47). Continuous positive airway pressure treatment can reduce hypoxia and normalize blood oxygen saturation, thereby reducing sleep fragmentation and improving cognitive function. After continuous positive airway pressure treatment, restoration in abnormal baseline activation in the left inferior frontal gyrus, anterior cingulate cortex, and hippocampus (12) and an increase in task-related activation (66) were associated with a significant improvement in working memory performance.

Functional brain alterations during resting wakefulness in obstructive sleep apnea. Overall, studies show that there is a decrease in brain activity as indicated by decreased perfusion in the parietal cortex (22), bilateral parahippocampal gyri, and right lingual gyrus (43) in individuals with obstructive sleep apnea during resting wakefulness. Functional connectivity within dorsal and ventral attention networks as well as the default-mode network is decreased at rest, and this decrease is associated with worst cognitive performance (31). There is also decreased metabolism in the precuneus, middle and posterior cingulate gyrus, parieto-occipital cortex, and prefrontal cortex (84). These decreases might be due to compensatory mechanisms in response to blood flow alterations or blood gas changes in obstructive sleep apnea and are partly reversible with continuous positive airway pressure treatment (48; 54).

Summary findings on obstructive sleep apnea

(A) Summary of findings from fMRI studies in obstructive sleep apnea. During tasks, activation is reduced in the dorsolateral prefrontal cortex, anterior cingulate cortex, middle frontal gyrus, inferior frontal gyrus, cingulate...

Structural brain alterations in obstructive sleep apnea. Structural alterations in obstructive sleep apnea might correspond to neuronal damage resulting from intermittent hypoxia. Reduced cortical thickness has been found in individuals with obstructive sleep apnea in the precentral and postcentral gyri, ie, sensorimotor areas, corresponding to the upper airway musculature areas as well as temporal cortex and insula (53). Cortical thinning in the hippocampus and entorhinal cortex has been found to be related to disease severity and can be slowed down by continuous positive airway pressure treatment (63). In contrast, other studies reported greater cortical thickness in frontal regions (08; 17; 25), which were associated with obstructive sleep apnea severity and could, therefore, be reflective of edema and reactive cellular processes (08).

Gray matter volume decreases seem to be more widespread and encompass the prefrontal, postcentral gyrus, temporal, and parietal cortices as well as the anterior cingulate cortex, posterior hippocampus (CA3/dentate), thalamus, and cerebellum. Most of these changes have been associated with cognitive deficits or disease severity, and smaller hippocampal volume has been associated with excessive daytime sleepiness (83; 36; 06). In contrast, increases in gray matter volume seem to be restricted to the CA1, subiculum, and uncus parts of the hippocampus (83).

White matter integrity is also affected in individuals with obstructive sleep apnea. Mean diffusivity is lower (ie, water diffusion is more restricted) in the corpus callosum, sensorimotor cingulate cortex, corticospinal tract, insular cortex, basal ganglia, and limbic network (13; 69) and might be reversible after treatment with continuous positive airway pressure (63). In some individuals with obstructive sleep apnea, white matter hyperintensities can be observed on MRI scans and might reflect vascular damage that is associated with aging or comorbid hypertension (69).

Brain metabolite alterations in obstructive sleep apnea. The cognitive deficits in obstructive sleep apnea may also be related to the metabolite alterations in specific cerebral regions. The level of N-acetylaspartate/creatine has been found to be decreased in periventricular and frontal white matter (16), possibly reflecting poorer neuronal integrity and glial dysfunction. In addition, choline/creatine levels were increased in the thalamus (01) and temporal cortex (71), which might indicate reactive gliosis or maladaptive changes in membrane metabolism in response to hypoxia. In contrast, other studies have found increased N-acetylaspartate/creatine and choline/creatine ratios in the hippocampus, which correlated with greater obstructive sleep apnea severity (09; 02). Finally, some metabolite ratio alterations were reversible with continuous positive airway pressure treatment (62), whereas others were not (79).

Clinical applications

	• Although structural alterations observed with neuroimaging can reflect evidence of a disturbance in specific neurotransmission systems (eg, REM sleep behavior disorder) or long-term consequences of a sleep disorder (eg, the consequences of hypoxia in obstructive sleep apnea), the structural and functional alterations are more subtle and less generalizable in other sleep disorders, such as insomnia.
	• More large-scale studies and multisite datasets are needed to better identify the more subtle structural and functional alterations that are present in sleep disorders.
	• Neuroimaging has generated valuable insights into the understanding of the neurologic bases and consequences of different sleep disorders, thereby helping to better delineate sleep disorders, refine diagnoses, and help in the development of treatment approaches.

Neuroimaging can help track the progression of sleep disorders; for example, in REM sleep behavior disorder, the level of dopamine neurotransmission appears to be related to the progression of REM sleep behavior disorder. Nuclear imaging studies have also shown that lower dopamine receptor density is observed in subclinical REM sleep behavior disorder and later transitions to synucleinopathies, such as Parkinson disease and Lewy body dementia. However, it is unclear whether such dopamine abnormalities are a causal factor or consequence of REM sleep behavior disorder. In addition, resting state functional connectivity in the basal ganglia, compared to norms in a healthy population, could also be a marker of disease progression. It has been shown to be similar in REM sleep behavior disorder and in individuals with Parkinson disease; these findings need to be replicated in longitudinal studies (68).

Further, neuroimaging can help refine diagnoses more specifically for central hypersomnia disorders. Neuroimaging can be an additional tool to better delineate narcolepsy with cataplexy from narcolepsy without cataplexy or idiopathic hypersomnia. Neuroimaging can also shed light on the interaction between sleep disorders and processes, such as the glymphatic system, which has a circadian rhythm and increases during sleep, offering the opportunity to investigate the link between neurodegenerative diseases and sleep disorders, such as REM sleep behavior disorder or narcolepsy (29; 70).

The growing neuroimaging literature shows that insomnia is a multifaceted disorder that exhibits differences in brain function that are subtle and region-specific as well as state-specific (sleep vs. wakefulness). Therefore, neuroimaging can help in understanding subtypes of insomnia by better characterizing this heterogenous population using multiple metrics. Individuals with insomnia might have different structural and functional characteristics depending on which process is more affected.

Finally, neuroimaging can help assess the effect of a treatment intervention. For example, the effect of the first-line treatment for chronic insomnia, cognitive behavioral therapy for insomnia, on brain activity can be assessed with neuroimaging. The effect of continuous positive airway pressure treatment has been assessed in individuals with obstructive sleep apnea and shows a partial normalization of both symptoms and structural alterations in the hippocampus (12).

Media

References

01: Algin O, Gokalp G, Ocakoglu G, Ursavas A, Taskapilioglu O, Hakyemez B. Neurochemical–structural changes evaluation of brain in patients with obstructive sleep apnea syndrome. Eur J Radiol 2012;81(3):491-5. PMID 21300501
02: Alkan A, Sharifov R, Akkoyunlu ME, et al. MR spectroscopy features of brain in patients with mild and severe obstructive sleep apnea syndrome. Clin Imaging 2013;37(6):989-92. PMID 23993754
03: Altena E, Van Der Werf YD, Sanz-Arigita EJ, et al. Prefrontal hypoactivation and recovery in insomnia. Sleep 2008;31(9):1271-6. PMID 18788652
04: Bae YJ, Kim JM, Choi BS, et al. Altered brain glymphatic flow at diffusion-tensor MRI in rapid eye movement sleep behavior disorder. Radiology 2023;307(5):e221848. PMID 37158722
05: Baglioni C, Speigelhalder K, Regen W, et al. Insomnia disorder is associated with increased amygdala reactivity to insomnia-related stimuli. Sleep 2014;37(12):1907-17. PMID 25325493
06: Baima CB, Fim NC, Alves KF, de Lima Resende LA, Fonseca RG, Betting LE. Analysis of patients with obstructive sleep apnea with and without pharyngeal myopathy using brain neuroimaging. Sleep 2020;43(2):zsz216. PMID 31552419
07: Ballotta D, Talami F, Pizza F, et al. Hypothalamus and amygdala functional connectivity at rest in narcolepsy type 1. Neuroimage Clin 2021;31:102748. PMID 34252875
08: Baril AA, Gagnon L, Brayet P, et al. Gray matter hypertrophy and thickening with obstructive sleep apnea in middle-aged and older adults. Am J Respir Crit Care Med 2017;195(11):1509-18. PMID 28060546
09: Bartlett DJ, Rae C, Thompson CH, et al. Hippocampal area metabolites relate to severity and cognitive function in obstructive sleep apnea. Sleep Med 2004;5(6):593-6. PMID 15511707
10: Boucetta S, Montplaisir J, Zadra A, et al. Altered regional cerebral blood flow in idiopathic hypersomnia. Sleep 2017;40(10). PMID 28958044
11: Boucetta S, Salimi A, Dadar M, Jones B, Collins DL, Dang-Vu TT. Structural brain alterations associated with rapid eye movement sleep behavior disorder in Parkinson’s disease. Sci Rep 2016;6:26782. PMID 27245317
12: Castronovo V, Canessa N, Strambi LF, et al. Brain activation changes before and after PAP treatment in obstructive sleep apnea. Sleep 2009;32(9):1161-72. PMID 19750921
13: Chen HL, Huang CC, Lin HC, et al. White matter alteration and autonomic impairment in obstructive sleep apnea. J Clin Sleep Med 2020;16(2):293-302. PMID 31992402
14: Chen L, Shao Z, Xu Y, et al. Disrupted frontostriatal connectivity in primary insomnia: a DTI study. Brain Imaging Behav 2021;15(5):1-8. PMID 33651331
15: Chen MC, Chang C, Glover GH, Gotlib IH. Increased insula coactivation with salience networks in insomnia. Biol Psychol 2014;97:1-8. PMID 24412227
16: Cross N, Dang-Vu TT. Imaging of the sleep-disordered brain. In: Dringenberg H, editor. Handbook of sleep research, Volume 30. Academic Press, 2019:569-91.**
17: Cross NE, Memarian N, Duffy S, et al. Structural brain correlates of obstructive sleep apnoea in older adults at risk for dementia. Eur Respir J 2018;52(1):1800740. PMID 29973356
18: Dang-Vu TT, Gagnon J, Vendette M, Soucy J, Postuma RB, Montplaisir J. Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder. Neurology 2012;79:2302-6. PMID 23115214
19: Dauvilliers Y, Comte F, Bayard S, Carlander B, Zanca M, Touchon J. A brain PET study in patients with narcolepsy-cataplexy. J Neurol Neurosurg Psychiatry 2010;81(3):344-8. PMID 19850578
20: Dauvilliers Y, Evangelista E, de Verbizier D, Barateau L, Peigneux P. [18F]Fludeoxyglucose-positron emission tomography evidence for cerebral hypermetabolism in the awake state in narcolepsy and idiopathic hypersomnia. Front Neurol 2017;8:350. PMID 28775709
21: Drummond SPA, Walker M, Almklov E, Campos M, Anderson D, Straus LD. Neural correlates of working memory performance in primary insomnia. Sleep 2013;36(9):1307-16. PMID 23997363
22: Ficker JH, Feistel H, Moller M, Dertinger S, Siegfried W, Hahn EG. Changes in regional CNS perfusion in obstructive sleep apnea syndrome: initial SPECT studies with injected nocturnal 99mTc-HMPAO. [Article in German] Pneumologie 1997;51(9):926-30. PMID 9411446
23: Franzen PL, Siegle G, Jones NP, Buysse DJ. Elevated amygdala activation during voluntary emotion regulation in primary insomnia. Sleep 2013;36:A194.
24: Gan C, Ma K, Wang L, et al. Dynamic functional connectivity changes in Parkinson’s disease patients with REM sleep behavior disorder. Brain Res 2021;1764:147477. PMID 33852889
25: Gao J, Cao J, Chen J, et al. Brain morphology and functional connectivity alterations in patients with severe obstructive sleep apnea. Sleep Med 2023;111:62-9. PMID 37722341
26: Gong L, Shi M, Wang J, et al. The abnormal functional connectivity in the locus coeruleus-norepinephrine system associated with anxiety symptom in chronic insomnia disorder. Front Neurosci 2021;15:678465. PMID 34093121
27: Gool JK, Cross N, Fronczek R, et al. Neuroimaging in narcolepsy and idiopathic hypersomnia: from neural correlates to clinical practice. Current Sleep Medicine Reports 2020a;6(4):251-66.**
28: Gool JK, van der Werf YD, Lammers GJ, Fronczek R. The sustained attention to response task shows lower cingulo-opercular and frontoparietal activity in people with narcolepsy type 1: an fMRI study on the neural regulation of attention. Brain Sci 2020b;10(7):419. PMID 32630358
29: Hablitz LM, Plá V, Giannetto M, et al. Circadian control of brain glymphatic and lymphatic fluid flow. Nat Commun 2020;11(1):4411. PMID 32879313
30: Harper DG, Plante DT, Jensen JE, et al. Energetic and cell membrane metabolic products in patients with primary insomnia: a 31-phosphorus magnetic resonance spectroscopy study at 4 tesla. Sleep 2013;36(4):493-500. PMID 23564996
31: He Y, Shen J, Wang X, Wu Q, Liu J, Ji Y. Preliminary study on brain resting-state networks and cognitive impairments of patients with obstructive sleep apnea-hypopnea syndrome. BMC Neurol 2022;22(1):456. PMID 36476321
32: Holtbernd F, Romanzetti S, Oertel WH, et al. Convergent patterns of structural brain changes in rapid eye movement sleep behavior disorder and Parkinson’s disease on behalf of the German rapid eye movement sleep behavior disorder study group. Sleep 2021;44(3):zsaa199. PMID 32974664
33: Holub F, Petri R, Schiel J, et al. Associations between insomnia symptoms and functional connectivity in the UK Biobank cohort (n = 29,423). J Sleep Res 2023;32(2):e13790. PMID 36528860
34: Hong SB, Tae WS, Joo EY. Cerebral perfusion changes during cataplexy in narcolepsy patients. Neurology 2006;66(11):1747-9. PMID 16769955
35: Horovitz SG, Braun AR, Carr WS, et al. Decoupling of the brain’s default mode network during deep sleep. Proc Natl Acad Sci USA 2009;106:11376-81. PMID 19549821
36: Huang X, Tang S, Lyu X, Yang C, Chen X. Structural and functional brain alterations in obstructive sleep apnea: a multimodal meta-analysis. Sleep Med 2019;54:195-204.** PMID 30580194
37: Huang Z, Liang P, Jia X, et al. Abnormal amygdala connectivity in patients with primary insomnia: evidence from resting state fMRI. Eur J Radiol 2012;81(6):1288-95. PMID 21458943
38: Iranzo A, Lomena F, Stockner H, et al. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 2010;9(11):1070-7. PMID 20846908
39: Iranzo A, Santamaria J, Pujol J, Moreno A, Deus J, Tolosa E. Brainstem proton magnetic resonance spectroscopy in idiopathic REM sleep behavior disorder. Sleep 2002;25(8):867-70. PMID 12489892
40: Iranzo A, Tolosa E, Gelpi E, et al. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol 2013;12(5):443-53.** PMID 23562390
41: Jarvela M, Kananen J, Korhonen V, Huotari N, Ansakorpi H, Kiviniemi V. Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy. Commun Med (Lond) 2022;2:122. PMID 36193214
42: Joo EY, Hong SB, Tae WS, et al. Cerebral perfusion abnormality in narcolepsy with cataplexy. NeuroImage 2005;28(2):410-6. PMID 16098766
43: Joo EY, Tae WS, Han SJ, Cho JW, Hong SB. Reduced cerebral blood flow during wakefulness in obstructive sleep apnea-hypopnea syndrome. Sleep 2007;30(11):1515-20. PMID 18041484
44: Joo EY, Tae WS, Kim JH, Kim BT, Hong SB. Glucose hypometabolism of hypothalamus and thalamus in narcolepsy. Ann Neurol 2004;56(3):437-40. PMID 15349874
45: Kay DB, Buysse DJ. Hyperarousal and beyond: new insights to the pathophysiology of insomnia disorder through functional neuroimaging studies. Brain Sci 2017;7(3):23.** PMID 28241468
46: Kay DB, Karim HT, Soehner AM, et al. Sleep-wake differences in relative regional cerebral metabolic rate for glucose among patients with insomnia compared with good sleepers. Sleep 2016;39(10):1779-94. PMID 27568812
47: Khazaie H, Veronese M, Noori K, et al. Functional reorganization in obstructive sleep apnoea and insomnia: a systematic review of the resting-state fMRI. Neurosci Biobehav Rev 2017;77:219-31.** PMID 28344075
48: Kim JS, Seo JH, Kang MR, et al. Effect of continuous positive airway pressure on regional cerebral blood flow in patients with severe obstructive sleep apnea syndrome. Sleep Med 2017;32:122-8. PMID 28366323
49: Kim SJ, Lyoo IK, Lee YS, et al. Increased GABA levels in medial prefrontal cortex of young adults with narcolepsy. Sleep 2008;31(3):342-7. PMID 18363310
50: Kotagal V, Albin RL, Muller ML, et al. Symptoms of rapid eye movement sleep behavior disorder are associated with cholinergic denervation in Parkinson disease. Ann Neurol 2012;71(4):560-8. PMID 22522445
51: Leerssen J, Blanken TF, Pozzi E, et al. Brain structural correlates of insomnia severity in 1053 individuals with major depressive disorder: results from the ENIGMA MDD Working Group. Transl Psychiatry 2020;10(1):425. PMID 33293520
52: Li C, Liu Y, Yang N, et al. Functional connectivity disturbances of the locus coeruleus in chronic insomnia disorder. Nat Sci Sleep 2022;14:1341-50. PMID 35942365
53: Macey PM, Haris N, Kumar R, Thomas MA, Woo MA, Harper RM. Obstructive sleep apnea and cortical thickness in females and males. PLoS One 2018;13(3):e0193854. PMID 29509806
54: Maresky HS, Shpirer I, Klar MM, Levitt M, Sasson E, Tal S. Continuous positive airway pressure alters brain microstructure and perfusion patterns in patients with obstructive sleep apnea. Sleep Med 2019;57:61-9. PMID 30897457
55: Marques DR, Gomes AA, Caetano G, Castelo-Branco M. Insomnia disorder and brain’s default-mode network. Curr Neurol Neurosci Rep 2018;18(8):45. PMID 29886515
56: Meyer JS, Sakai F, Karacan I, Derman S, Yamamoto M. Sleep apnea, narcolepsy, and dreaming: regional cerebral hemodynamics. Ann Neurol 1980;7(5):479-85. PMID 7396426
57: Miller CB, Rae CD, Green MA, et al. An objective short sleep insomnia disorder subtype is associated with reduced brain metabolite concentrations in vivo: a preliminary magnetic resonance spectroscopy assessment. Sleep 2017;40(11). PMID 28958033
58: Miyamoto M, Miyamoto T, Kubo J, Yokota N, Hirata K, Sato T. Brainstem function in rapid eye movement sleep behavior disorder: the evaluation of brainstem function by proton MR spectroscopy (1H‐MRS). Psychiatry Clin Neurosci 2000;54(3):350-1. PMID 11186109
59: Moghaddam HS, Mohammadi E, Dolatshahi M, et al. White matter microstructural abnormalities in primary insomnia: a systematic review of diffusion tensor imaging studies. Prog Neuropsychopharmacol Biol Psychiatry 2021;105:110132. PMID 33049323
60: Nie X, Shao Y, Liu SY, et al. Functional connectivity of paired default mode network subregions in primary insomnia. Neuropsych Dis Treat 2015;11:3085-93. PMID 26719693
61: Nofzinger EA, Buysse DJ, Germain A, Price JC, Miewald JM, Kupfer DJ. Functional neuroimaging evidence for hyperarousal in insomnia. Am J Psychiatry 2004;161(11):2126-8. PMID 15514418
62: O’Donoghue FJ, Wellard RM, Rochford PD, et al. Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment. Sleep 2012;35(1):41-8. PMID 22215917
63: Owen JE, BenediktsdÓttir B, Gislason T, Robinson SR. Neuropathological investigation of cell layer thickness and myelination in the hippocampus of people with obstructive sleep apnea. Sleep 2018;42(1). PMID 30346595
64: Pomares FB, Boucetta S, Lachapelle F, et al. Beyond sleepy: structural and functional changes of the default-mode network in idiopathic hypersomnia. Sleep 2019;42(11):zsz156. PMID 31328786
65: Ponz A, Khatami R, Poryazova R, et al. Abnormal activity in reward brain circuits in human narcolepsy with cataplexy. Ann Neurol 2010;67(2):190-200. PMID 20225193
66: Prilipko O, Huynh N, Schwartz S, et al. The effects of CPAP treatment on task positive and default mode networks in obstructive sleep apnea patients: an fMRI Study. PLoS One 2012;7(12):e47433. PMID 23227139
67: Reiss AL, Hoeft F, Tenforde AS, et al. Anomalous hypothalamic responses to humor in cataplexy. PLoS One 2008;3(5):e2225. PMID 18493621
68: Rolinski M, Griffanti L, Piccini P, et al. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease. Brain 2016;139(Pt 8):2224-34. PMID 27297241
69: Rostampour M, Noori K, Heidari M, et al. White matter alterations in patients with obstructive sleep apnea: a systematic review of diffusion MRI studies. Sleep Med 2020;75:236-45. PMID 32861061
70: Sahu M, Tripathi R, Jha NK, Jha SK, Ambasta RK, Kumar P. Cross talk mechanism of disturbed sleep patterns in neurological and psychological disorders. Neurosci Biobehav Rev 2022;140:104767. PMID 35811007
71: Sarchielli P, Presciutti O, Alberti A, et al. A 1H magnetic resonance spectroscopy study in patients with obstructive sleep apnea. Eur J Neurol 2008;15(10):1058-64. PMID 18717729
72: Scherfler C, Frauscher B, Schocke M, et al. White and gray matter abnormalities in idiopathic rapid eye movement sleep behavior disorder: a diffusion‐tensor imaging and voxel‐based morphometry study. Ann Neurol 2011;69(2):400-7. PMID 21387382
73: Schiel JE, Holub F, Petri R, et al. Affect and arousal in insomnia: through a lens of neuroimaging studies. Curr Psychiatry Rep 2020;22(9):44. PMID 32661938
74: Schwartz S, Ponz A, Poryazova R, et al. Abnormal activity in hypothalamus and amygdala during humour processing in human narcolepsy with cataplexy. Brain 2008;131(Pt 2):514-22. PMID 18094020
75: Si XL, Gu LY, Song Z, et al. Different perivascular space burdens in idiopathic rapid eye movement sleep behavior disorder and Parkinson’s disease. Front Aging Neurosci 2020;12:580853. PMID 33250763
76: Suh S, Kim H, Dang-Vu TT, Joo E, Shin C. Cortical thinning and altered cortico-cortical structural covariance of the default mode network in patients with persistent insomnia symptoms. Sleep 2016;39(1):161-71. PMID 26414892
77: Thannickal TC, Moore RY, Nienhuis R, et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000;27(3):469-74. PMID 11055430
78: Tonon C, Franceschini C, Testa C, et al. Distribution of neurochemical abnormalities in patients with narcolepsy with cataplexy: an in vivo brain proton MR spectroscopy study. Brain Res Bull 2009;80(3):147-50. PMID 19463917
79: Tonon C, Vetrugno R, Lodi R, et al. Proton magnetic resonance spectroscopy study of brain metabolism in obstructive sleep apnoea syndrome before and after continuous positive airway pressure treatment. Sleep 2007;30(3):305-11. PMID 17425226
80: Unger MM, Belke M, Menzler K, et al. Diffusion tensor imaging in idiopathic REM sleep behavior disorder reveals microstructural changes in the brainstem, substantia nigra, olfactory region, and other brain regions. Sleep 2010;33:767-73. PMID 20550017
81: Wakasugi N, Togo H, Mukai Y, et al. Prefrontal network dysfunctions in rapid eye movement sleep behavior disorder. Parkinsonism Relat Disord 2021;85:72-7. PMID 33744693
82: Weihs A, Frenzel S, Bi H, et al. Lack of structural brain alterations associated with insomnia: findings from the ENIGMA-Sleep Working Group. J Sleep Res 2023;32(5):e13884. PMID 36944539
83: Weng HH, Tsai YH, Chen CF, et al. Mapping gray matter reductions in obstructive sleep apnea: an activation likelihood estimation meta-analysis. Sleep 2014;37(1):167-75. PMID 24470705
84: Yaouhi K, Bertran F, Clochon P, et al. A combined neuropsychological and brain imaging study of obstructive sleep apnea. J Sleep Res 2009;18(1):36-48. PMID 19250174
85: Zou G, Li Y, Liu J, et al. Altered thalamic connectivity in insomnia disorder during wakefulness and sleep. Hum Brain Mapp 2021;42(1):259-70. PMID 33048406
86: References especially recommended by the author or editor for general reading.

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Authors

Florence Pomares PhD

Dr. Pomares of Centre de Recherche de l'IUGM in Montreal has no relevant financial relationships to disclose.
See Profile
Nathan Cross PhD

Dr. Cross of Concordia University has no relevant financial relationships to disclose.
See Profile
Aurore A Perrault PhD

Dr. Perrault of Concordia University has no relevant financial relationships to disclose.
See Profile
Thien Thanh Dang-Vu MD PhD FAASM

Dr. Dang-Vu of Concordia University and CIUSSS du Centre-Sud-de-l’île-de-Montréal received speaker fees from Eisai, consultant fees from Idorsia, and research grants from Jass Pharmaceuticals and Paladin Labs as principal investigator.
See Profile

Editor

Antonio Culebras MD FAAN FAHA FAASM

Dr. Culebras of SUNY Upstate Medical University at Syracuse has no relevant financial relationships to disclose.
See Profile

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Neuroimaging of sleep disorders

Also Relevant

Environmental and behavioral sleep disorders
Idiopathic hypersomnia
Narcolepsy
Obstructive sleep apnea
Rapid eye movement sleep behavior disorder

Neuroimaging of sleep disorders

Neuroimaging of sleep disorders

Introduction

Overview

Key points

Historical note and terminology

Description

Insomnia

Narcolepsy and idiopathic hypersomnia

REM sleep behavior disorder

Obstructive sleep apnea

Clinical applications

Media

References

Contributors

Authors

Editor

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Brain death/death by neurologic criteria

Hypersomnolence

Hepatic encephalopathy

Bowel dysfunction in neurologic disorders

Coma due to primary brainstem and diencephalic lesions

Transient visual loss

Fatal familial insomnia

Sleep and mental disorders

Neuroimaging of sleep disorders

Introduction

Overview

Key points

Historical note and terminology

Description

Insomnia

Narcolepsy and idiopathic hypersomnia

REM sleep behavior disorder

Obstructive sleep apnea

Clinical applications

Media

References

Contributors

Authors

Editor

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Brain death/death by neurologic criteria

Hypersomnolence

Hepatic encephalopathy

Bowel dysfunction in neurologic disorders

Coma due to primary brainstem and diencephalic lesions

Transient visual loss

Fatal familial insomnia

Sleep and mental disorders

This is an article preview.
Start a Free Account
to access the full version.