Abstract
Objectives: This work aims to explore the changes of functional connectivity (FC) within the hippocampus network in patients with moderate and severe obstructive sleep apnea (OSA) and its correlation with neurocognitive dysfunction to explore the potential neurophysiological mechanism.Methods: A total of 32 treatment-naïve patients with moderate or severe OSA and 26 healthy controls (HCs), matched in age, gender, and education, underwent the evaluations of Epworth Sleep Scale, neurocognitive function, full-night polysomnography, and resting-state functional magnetic resonance imaging. The FC map of the hippocampus to other brain areas was compared among 15 OSA patients and 15 HCs with little head motion. Finally, the correlation between hippocampus FC strength and respiratory sleep parameters and neurocognitive assessments was analyzed.Results: Compared with HCs, the right hippocampus showed a significantly decreased FC with the bilateral insular lobe, right thalamus, and right anterior cingulate gyrus (ACG) and an increased FC with the right superior and middle temporal gyrus, left posterior cingulate gyrus, and left angular gyrus in the patients with OSA. The left hippocampus presented a significantly decreased FC with the left anterior cerebellum in patients with OSA. In addition, the aberrant right hippocampal FC with the right ACG was significantly correlated with disease severity and disrupted sleep architecture in the OSA group. Furthermore, after adjusting the related confounding factors, the FC strength between the right hippocampus, right insular lobe, and right thalamus was positively associated with the scores of Stroop Color–Word Test (SCWT) or Hopkins Verbal Learning Test—Revised (HVLT-R), while the FC between the right hippocampus and the right middle temporal gyrus was negatively correlated with the scores of HVLT-R. The right hippocampus FC with right superior temporal gyrus, left angular gyrus, and ACG were all negatively related to the scores of the symbol coding test (r = −0.642, p = 0.045; r = −0.638, p = 0.047; r = −0.753, p = 0.012), respectively. The FC between the left hippocampal and the left anterior cerebellar lobe showed a positive relationship with the scores of HVLT-R (r = 0.757, p = 0.011) and CPT-3D (r = −0.801, p = 0.005).Conclusion: The hippocampus presented abnormal FC with the cerebral and cerebellar regions extensively in OSA, and the correlation between abnormal hippocampal network FC and neurocognitive dysfunction in OSA suggests a promising insight to explore the potential biomarker and pathophysiologic mechanism of neurocognitive dysfunction of OSA.
Highlights
Obstructive sleep apnea (OSA) syndrome is one of the commonest types of sleep disorder, of which the prevalence of moderate-to-severe OSA in the population is high, with up to 49.7% in men and 23.4% in women [1]
Resting-state functional magnetic resonance imaging (fMRI), an advanced fMRI technology to evaluate brain activity in the spontaneous state, has demonstrated abnormality in regional homogeneity [15], global and regional functional connectivity (FC) [16], and amplitude of low-frequency fluctuation [17] within individuals with OSA. rs-fMRI is a useful tool to detect the changes of brain functional activities in neurodegenerative diseases [18, 19], in which seed-based FC is a widely applied approach to evaluate the functional synchronicity between a specific region of interest and the rest of the brain voxels by calculating the correlation coefficients of blood oxygen level-dependent time series signals among these brain regions [20]
After adjusting the confounding factors of age, education, BMI, smoking, and alcohol drinking index, we found that the FC between the right hippocampus and the anterior cingulate gyrus was positively correlated with AHI and oxygen desaturation index (ODI) and negatively correlated with mean SaO2 among the OSA group, which indicated that chronic intermittent hypoxemia
Summary
Obstructive sleep apnea (OSA) syndrome is one of the commonest types of sleep disorder, of which the prevalence of moderate-to-severe OSA in the population is high, with up to 49.7% in men and 23.4% in women [1]. Repetitive partial or complete obstruction of the upper airway during sleep leads to two prominent pathophysiological characteristics of OSA: nocturnal intermittent hypoxia and sleep fragmentation/disruption [1]. The brain, especially the cerebral cortex and hippocampus, is extremely vulnerable to hypoxia and oxidative stress, and the above-mentioned pathophysiological changes in the brain of OSA patients could induce the overproduction of neuroinflammatory cytokines and cellular dysfunction, resulting in chronic damage and even apoptosis of neuronal cells, and eventually lead to neurocognitive dysfunction [3]. In the recent decades, neuroimaging technologies, including functional magnetic resonance imaging (fMRI), voxel-based morphometry, magnetic resonance spectroscopy, diffusion tensor imaging, etc., were introduced in studies of OSA to investigate the changes of brain function and structures and explore the potential neuropathologic mechanism of neurocognitive impairment in OSA [6,7,8,9]. Abnormal FC was found in multiple brain regions including the insula [16, 21], amygdala sub-regions [22], prefrontal cortex [23], and default-mode network [24,25,26] in OSA patients
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