ABSTRACT
Obstructive sleep apnea (OSA), a common respiratory sleep disorder, is often associated with mild cognitive impairment (MCI), which is a precursor stage to Alzheimer's disease (AD). However, the neuroimaging changes in patients with OSA with/without MCI are still under discussion. This study aimed to investigate the temporal variability of spontaneous brain activity in OSA. Fifty-two OSA patients (26 with OSA with MCI (OSA-MCI), 26 OSA without MCI (OSA-nMCI), and 26 healthy controls (HCs) underwent MRI scans and scale questionnaires. A dynamic amplitude of low-frequency fluctuation (dALFF) evaluation was performed to examine the time-varying nature of OSA-MCI and OSA-nMCI. Compared with OSA-MCI, OSA-nMCI had increased dALFF in the posterior cerebellar and right superior frontal gyrus; compared with HCs, OSA-nMCI patients showed increased dALFF in the right posterior cerebellum. A positive correlation between the bilateral posterior cerebellar lobes and right superior frontal gyrus was observed in OSA-MCI patients; however, in OSA-nMCI patients, a positive correlation was observed only between the bilateral posterior cerebellar lobes. The dALFF value of the left posterior cerebellar lobe was positively correlated with the apnea-hypopnea index (AHI), epworth sleepiness scale (ESS) score, and arousal index in OSA-nMCIs, while the dALFF value of the right posterior cerebellum was positively correlated with the AHI and negatively correlated with the lowest oxygen saturation (SaO2). This study argues that OSA-nMCIs and OSA-MCIs exhibit different temporal variabilities in dynamic brain functions, OSA-nMCIs may have variable intermediate states. We concluded that the functional abnormalities of the cerebellar-prefrontal cortex pathway in OSA-MCIs may cause cognitive impairment with OSA.
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Objective: The purpose of this study was to investigate the dynamic functional network connectivity (FNC) and its relationship with cognitive function in obstructive sleep apnea (OSA) patients from normal cognition (OSA-NC) to mild cognitive impairment (OSA-MCI). Materials and methods: Eighty-two male OSA patients and 48 male healthy controls (HC) were included in this study. OSA patients were classified to OSA-MCI (n = 41) and OSA-NC (n = 41) based on cognitive assessments. The independent component analysis was used to determine resting-state functional networks. Then, a sliding-window approach was used to construct the dynamic FNC, and differences in temporal properties of dynamic FNC and functional connectivity strength were compared between OSA patients and the HC. Furthermore, the relationship between temporal properties and clinical assessments were analyzed in OSA patients. Results: Two different connectivity states were identified, namely, State I with stronger connectivity and lower frequency, and State II with lower connectivity and relatively higher frequency. Compared to HC, OSA patients had a longer mean dwell time and higher fractional window in stronger connectivity State I, and opposite result were found in State II, which was mainly reflected in OSA-MCI patients. The number of transitions was an increasing trend and positively correlated with cognitive assessment in OSA-MCI patients. Compared with HC, OSA patients showed extensive abnormal functional connectivity in stronger connected State I and less reduced functional connectivity in lower connected State II, which were mainly located in the salience network, default mode network, and executive control network. Conclusion: Our study found that OSA patients showed abnormal dynamic FNC properties, which was a continuous trend from HC, and OSA-NC to OSA-MCI, and OSA patients showed abnormal dynamic functional connectivity strength. The number of transformations was associated with cognitive impairment in OSA-MCI patients, which may provide new insights into the neural mechanisms in OSA patients.
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Purpose: Previous studies found abnormal low-frequency spontaneous brain activity related to cognitive impairment in patients with obstructive sleep apnea (OSA). However, it is unclear if low-frequency spontaneous brain activity is related to specific frequency bands in OSA patients. In this study, we used the amplitude of low-frequency fluctuation (ALFF) method in patients with OSA to explore characteristics of spontaneous brain activity in the classical (0.01-0.1 Hz) and five sub-frequency bands (slow-2 to slow-6) and analyzed the relationship between spontaneous brain activity and clinical evaluation was analyzed. Patients and methods: Resting-state magnetic resonance imaging data and clinical assessments were collected from 52 newly-diagnosed OSA patients and 62 healthy controls (HCs). We calculated the individual group ALFF values in the classical and five different sub-frequency bands. A two-sample t-test compared ALFF differences, and one-way analysis of variance explored interactions in frequency bands between the two groups. Results: ALFF values in the OSA group were lower than those in the HC group in the bilateral precuneus/posterior cingulate cortex, bilateral angular gyrus, left inferior parietal lobule, brainstem, and right fusiform gyrus. In contrast, ALFF values in the OSA group were higher than those in the HC group in the bilateral cerebellum posterior lobe, bilateral superior frontal gyrus, bilateral middle frontal gyrus, left inferior frontal gyrus, left inferior temporal gyrus, and left fusiform gyrus. Some ALFF values in altered brain regions were associated with body mass index, apnea-hypopnea index, neck circumference, snoring history, minimum SaO2, average SaO2, arousal index, oxygen reduction index, deep sleep period naming, abstraction, and delayed recall in specific frequency bands. Conclusion: Our results indicated the existence of frequency-specific differences in spontaneous brain activity in OSA patients, which were related to cognitive and other clinical symptoms. This study identified frequency-band characteristics related to brain damage, expanded the cognitive neuroimaging mechanism, and provided additional OSA neuroimaging markers.
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White matter (WM) fiber alterations in patients with obstructive sleep apnea (OSA) is associated with cognitive impairment, which can be alleviated by continuous positive airway pressure (CPAP). In this study, we aimed to investigate the changes in WM in patients with OSA at baseline (pre-CPAP) and 3 months after CPAP adherence treatment (post-CPAP), and to provide a basis for understanding the reversible changes after WM alteration in this disease. Magnetic resonance imaging (MRI) was performed on 20 severely untreated patients with OSA and 20 good sleepers. Tract-based spatial statistics was used to evaluate the fractional anisotropy (FA), mean diffusion coefficient, axial diffusion coefficient, and radial diffusion coefficient (RD) of WM. To assess the efficacy of treatment, 20 patients with pre-CPAP OSA underwent MRI again 3 months later. A correlation analysis was conducted to evaluate the relationship between WM injury and clinical evaluation. Compared with good sleepers, patients with OSA had decreased FA and increased RD in the anterior thalamic radiation, forceps major, inferior fronto-occipital tract, inferior longitudinal tract, and superior longitudinal tract, and decreased FA in the uncinate fasciculus, corticospinal tract, and cingulate gyrus (P < 0.05). No significant change in WM in patients with post-CPAP OSA compared with those with pre-CPAP OSA. Abnormal changes in WM in untreated patients with OSA were associated with oxygen saturation, Montreal cognitive score, and the apnea hypoventilation index. WM fiber was extensively alteration in patients with severe OSA, which is associated with cognitive impairment. Meanwhile, cognitive recovery was not accompanied by reversible changes in WM microstructure after short-term CPAP therapy.
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Purpose: This study aimed to explore the alterations in spontaneous brain activity in obstructive sleep apnea (OSA) using percent amplitude of fluctuation (PerAF) and investigate the relationship between abnormal spontaneous brain activity and cognitive impairment in OSA. Patients and Methods: Overall, 52 patients with moderate to severe OSA and 61 healthy controls (HCs) were eventually enrolled in this study. All participants underwent resting-state functional magnetic resonance (rs-fMRI) and T1-weighted imaging. The PerAF was calculated and compared between patients with OSA and HCs, with voxel level P < 0.001 and cluster level P < 0.05 corrected with Gaussian Random Field was be considered statistically different. A partial correlation analysis was used to assess the relationship between altered PerAF and clinical assessments in patients with OSA. Results: Compared to HCs, patients with OSA had significantly lower PerAF values in the right rectal gyrus and left superior frontal gyrus, but higher PerAF values in the right cerebellum posterior lobe and left middle frontal gyrus. The PerAF values of some specific regions in patients with OSA correlated with sleep efficiency and Montreal Cognitive Assessment scores. Additionally, support vector machine analysis showed that PerAF values in all differential brain regions could differentiate patients with OSA from HCs with good accuracy. Conclusion: Specific brain areas in OSA patients may exhibit aberrant neuronal activity, and these anomalies may be linked to decreased cognitive performance. This discovery offers fresh perspectives on these patients' neurocognition.
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Background and purpose: Previous studies have found that abnormal local spontaneous brain activity in patients with obstructive sleep apnea (OSA) was associated with cognitive impairment, and dynamic functional connections can capture the time changes of functional connections during magnetic resonance imaging acquisition. The purpose of this study was to investigate the dynamic characteristics of regional brain connectivity and its relationship with cognitive function in patients with OSA and to explore whether the dynamic changes can be used to distinguish them from healthy controls (HCs). Methods: Seventy-nine moderate and severe male OSA patients without any treatment and 84 HCs with similar age and education were recruited, and clinical data and resting functional magnetic resonance imaging data were collected. The dynamic regional homogeneity (dReHo) was calculated using a sliding window technique, and a double-sample t-test was used to test the difference in the dReHo map between OSA patients and HCs. We explored the relationship between dReHo and clinical and cognitive function in OSA patients using Pearson correlation analysis. A support vector machine was used to classify the OSA patients and HCs based on abnormal dReHo. Result: Compared with HCs, OSA patients exhibited higher dReHo values in the right medial frontal gyrus and significantly lower dReHo values in the right putamen, right superior temporal gyrus, right cingulate gyrus, left insula and left precuneus. The correlation analysis showed that the abnormal dReHo values in multiple brain regions in patients with OSA were significantly correlated with nadir oxygen saturation, the oxygen depletion index, sleep period time, and Montreal cognitive assessment score. The support vector machine classification accuracy based on the dReHo difference in brain regions was 81.60%, precision was 81.01%, sensitivity was 81.01%, specificity was 82.14%, and area under the curve was 0.89. Conclusion: The results of this study suggested that there was abnormal dynamic regional spontaneous brain activity in patients with OSA, which was related to clinical and cognitive evaluation and can be used to distinguish OSA patients from HCs. The dReHo is a potential objective neuroimaging marker for patients with OSA that can further the understanding of the neuropathological mechanism of patients with OSA.
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The hippocampus is involved in various cognitive function, including memory. Hippocampal structural and functional abnormalities have been observed in patients with obstructive sleep apnoea (OSA), but the functional connectivity (FC) patterns among hippocampal subdivisions in OSA patients remain unclear. The purpose of this study was to investigate the changes in FC between hippocampal subdivisions and their relationship with neurocognitive function in male patients with OSA. Resting-state fMRI were obtained from 46 male patients with untreated severe OSA and 46 male good sleepers. The hippocampus was divided into anterior, middle, and posterior parts, and the differences in FC between hippocampal subdivisions and other brain regions were determined. Correlation analysis was used to explore the relationships between abnormal FC of hippocampal subdivisions and clinical characteristics in patients with OSA. Our results revealed increased FC in the OSA group between the left anterior hippocampus and left middle temporal gyrus; between the left middle hippocampus and the left inferior frontal gyrus, right anterior central gyrus, and left anterior central gyrus; between the left posterior hippocampus and right middle frontal gyrus; between the right middle hippocampus and left inferior frontal gyrus; and between the right posterior hippocampus and left middle frontal gyrus. These FC abnormalities predominantly manifested in the sensorimotor network, fronto-parietal network, and semantic/default mode network, which are closely related to the neurocognitive impairment observed in OSA patients. This study advances our understanding of the potential pathophysiological mechanism of neurocognitive dysfunction in OSA.
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Background and Objectives: Obstructive sleep apnea (OSA) is the most common sleep disorder and previous studies have shown that OSA patients suffer from brain network impairments associated with cognitive deficits, and continuous positive airway pressure (CPAP) treatment can improve clinical symptoms. However, the relationship between CPAP treatment and brain network changes remains unclear. This study explored the characteristics of brain network changes in OSA patients before (pre-CPAP) and after one month of CPAP treatment (post-CPAP). Methods: We collected data, including sleep monitoring, clinical assessment, and magnetic resonance imaging scans, from 21 OSA patients and 21 age-matched healthy controls (HCs). Voxel-level degree centrality (DC) was used to assess whole-brain network connectivity characteristics, a two-sample t-test was used to compare network differences between pre-CPAP OSA patients and HCs, and a paired sample t-test was used to compare the characteristics of brain network changes in OSA patients before and after treatment. The correlations between the DC value and each of the clinical variables were analyzed in the OSA patients. Results: Compared with HCs, pre-CPAP OSA patients showed increased DC values in the bilateral cerebellar posterior lobes (CPLs) and decreased DC values in the right superior temporal gyrus, left superior frontal gyrus and right middle frontal gyrus. Compared with pre-CPAP OSA patients, post-CPAP OSA patients showed reduced DC values in the bilateral CPL and increased DC values in several brain regions in the frontal, temporal, and insular lobes after CPAP treatment. The Montreal Cognitive Assessment MoCA (MoCA) scores were positively correlated with the DC value of the bilateral cerebellum posterior lobe, right middle temporal gyrus, left superior temporal gyrus, left paracentral lobule and left paracentral lobule. Also, Pittsburgh Sleep Quality Index (PSQI) scores were negatively correlated with the DC value of the right middle temporal gyrus in post-CPAP OSA patients. Conclusion: CPAP treatment can effectively reverse the compensatory response of the bilateral CPL and functional network damage brought about by OSA, which may provide potential neuroimaging biomarkers for CPAP treatment evaluation.
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PURPOSE: Previous studies have demonstrated abnormal local spontaneous brain activity in the conventional frequency bands (0.01-0.08 Hz) in obstructive sleep apnea (OSA). However, it is not clear whether these abnormalities are associated with the specific frequency band of low-frequency oscillations or whether it can be improved with a continuous positive airway pressure (CPAP) treatment. This study aimed to investigate the regional homogeneity (ReHo) in specific frequency at baseline (pre-CPAP) and after one month of CPAP adherence treatment (post-CPAP) in OSA patients. METHODS: Twenty-one patients with moderate-to-severe OSA and 21 age- and sex-matched healthy controls (HCs) were included in the final analysis. ReHo was calculated in three different frequency bands (typical frequency band: 0.01-0.1 Hz; slow-5 band: 0.01-0.027 Hz; slow-4 band: 0.027-0.073 Hz), respectively. A partial correlational analysis was performed to assess the relationship between altered ReHo and clinical evaluation. RESULTS: OSA patients revealed increased ReHo in the brainstem, bilateral inferior temporal gyrus (ITG)/fusiform, and right-cerebellum posterior lobe (CPL), and decreased ReHo in the bilateral inferior parietal lobule (IPL), right superior temporal gyrus (STG), and left precentral gyrus (PG) compared to HC groups in different frequency bands. Significantly changed ReHo in the bilateral middle temporal gyrus (MTG), PG, medial frontal gyrus (MFG), supplementary motor area (SMA), CPL, IPL, left superior frontal gyrus (SFG), ITG, MTG, and right STG were observed between post-CPAP and pre-CPAP OSA patients, which was associated with specific frequency bands. The altered ReHo in specific frequency bands was correlated with Montreal cognitive assessment score, Epworth sleepiness scale, and apnea hypopnea index in pre-CPAP OSA patients. CONCLUSION: These findings indicate that OSA has frequency-related abnormalities of spontaneous neural activity before and after short-term CPAP treatment, which might contribute to a better understanding of local neural psychopathology and may serve as potential biomarkers for clinical CPAP treatment.
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The insular cortex is a cortical regulatory area involved in dyspnea, cognition, emotion, and sensorimotor function. Previous studies reported that obstructive sleep apnea (OSA) shows insular tissue damage and abnormal functional connections for the whole insula. The insula can be divided into different subregions with distinct functional profiles, including the ventral anterior insula (vAI) participating in affective processing, dorsal anterior insula (dAI) involved in cognitive processing, and posterior insula (PI) involved in the processing of sensorimotor information. However, the functional connectivity (FC) of these insular subregions in OSA has yet to be established. Hence, the purpose of this study was to explore the resting-state FC of the insular subregions with other brain areas and its relationship with clinical symptoms of OSA. Resting-state functional magnetic resonance imaging data from 83 male OSA patients and 84 healthy controls were analyzed by whole-brain voxel-based FC using spherical seeds from six insular subregions, namely, the bilateral vAI, dAI, and PI, to identify abnormalities in the insular subregions network and related brain regions. Ultimately, the Pearson correlation analysis was carried out between the dysfunction results and the neuropsychological tests. Compared with the healthy control group, the OSA patients exhibited disturbed FC from the dAI to areas relevant to cognition, such as the bilateral cerebellum posterior lobe, superior frontal gyrus, right middle frontal gyrus and middle temporal gyrus; decreased FC from the vAI to areas linked with emotion, such as the bilateral fusiform gyrus, superior parietal lobule, precuneus and cerebellum posterior lobe; and abnormal FC from the PI to the brain regions involved in sensorimotor such as the bilateral precentral gyrus, right superior/middle temporal gyrus and left superior frontal gyrus. The linear regression result showed that the apnea-hypopnea index was positively correlated with the increased FC between the right PI and the right precuneus (after Bonferroni correlation, P < 0.001) In conclusion, the abnormal FC between insular subregions and other brain regions were related to cognitive, emotional and sensorimotor networks in OSA patients. These results may provide a new imaging perspective for further understanding of OSA-related cognitive and affective disorders.
