Abstract
The present study was aimed to evaluate resting-state functional connectivity and topological properties of brain networks in narcolepsy patients compared with healthy controls. Resting-state fMRI was performed in 26 adult narcolepsy patients and 30 matched healthy controls. MRI data were first analyzed by group independent component analysis, then a graph theoretical method was applied to evaluate the topological properties in the whole brain. Small-world network parameters and nodal topological properties were measured. Altered topological properties in brain areas between groups were selected as region-of-interest seeds, then the functional connectivity among these seeds was compared between groups. Partial correlation analysis was performed to evaluate the relationship between the severity of sleepiness and functional connectivity or topological properties in the narcolepsy patients. Twenty-one independent components out of 48 were obtained. Compared with healthy controls, the narcolepsy patients exhibited significantly decreased functional connectivity within the executive and salience networks, along with increased functional connectivity in the bilateral frontal lobes within the executive network. There were no differences in small-world network properties between patients and controls. The altered brain areas in nodal topological properties between groups were mainly in the inferior frontal cortex, basal ganglia, anterior cingulate, sensory cortex, supplementary motor cortex, and visual cortex. In the partial correlation analysis, nodal topological properties in the putamen, anterior cingulate, and sensory cortex as well as functional connectivity between these regions were correlated with the severity of sleepiness (sleep latency, REM sleep latency, and Epworth sleepiness score) among narcolepsy patients. Altered connectivity within the executive and salience networks was found in narcolepsy patients. Functional connection changes between the left frontal cortex and left caudate nucleus may be one of the parameters describing the severity of narcolepsy. Changes in the nodal topological properties in the left putamen and left posterior cingulate, changes in functional connectivity between the left supplementary motor area and right occipital as well as in functional connectivity between the left anterior cingulate gyrus and bilateral postcentral gyrus can be considered as a specific indicator for evaluating the severity of narcolepsy.
Highlights
Narcolepsy is a chronic sleep disorder with the main symptoms of excessive daytime sleepiness (EDS), accompanied by the occurrence of rapid eye-movements (REM) and daytime sleep attacks, especially in monotonous situations [1]
There were no significant differences between narcolepsy patients and healthy controls in age, gender, and body mass index (BMI)
Forty-eight components were obtained, 21 of which were selected as the resting-state network: 2 components in the language network, 3 in the default mode network (DMN), 3 in the visual network, 3 in the executive network, 3 in the sensorimotor network, 2 in the salience network, 4 in the attention network, and the remaining component in the cerebellum (Fig. S1)
Summary
Narcolepsy is a chronic sleep disorder with the main symptoms of excessive daytime sleepiness (EDS), accompanied by the occurrence of rapid eye-movements (REM) and daytime sleep attacks, especially in monotonous situations [1]. The pathology of narcolepsy is caused by the apoptosis of hypothalamic neurons producing hypocretin, a wake-promoting neurotransmitter that can be measured in the cerebrospinal fluid [2, 3]. Sleep-onset REM is a characteristic of the sleep architecture in narcolepsy patients due to the dysfunctional hypocretin [1]. It has been demonstrated that narcolepsy patients have an 85%–95% reduction in the number of hypocretin neurons [4, 5]. These neurons project extensively to most areas of the brain, and it has been demonstrated that hypocretin and its receptors play important roles in many physiological activities, such as feeding, energy homeostasis, the sleep-wake cycle, and neuroendocrine systems [2]
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