The Effect of Single-Night Continuous Positive Airway Pressure on Spontaneous Brain Activity in Patients with Severe Obstructive Sleep Apnea

Research Background

Obstructive sleep apnea (OSA) is a common chronic sleep-related breathing disorder characterized by partial or complete closure of the airway during sleep. This condition leads to repeated intermittent hypoxia, carbon dioxide retention, and sleep fragmentation. It has been reported that the prevalence of severe OSA is approximately 20% among adult males and 10% among postmenopausal females. Additionally, a study involving 38,000 Russian citizens showed that 48.9% of participants exhibited an apnea-hypopnea index (AHI) ≥ 5, 18.1% had an AHI ≥ 15, and 4.5% had an AHI ≥ 30. OSA can cause serious health complications including heart disease, hypertension, and gastroesophageal reflux. However, the specific mechanisms underlying brain dysfunction in OSA patients remain unclear.

Continuous positive airway pressure (CPAP) is the preferred treatment for moderate to severe OSA patients. Even a single night of CPAP treatment can quickly correct intermittent hypoxia, significantly reduce sleep fragmentation, and markedly increase the proportions of slow-wave and rapid eye movement (REM) sleep. Additionally, some severe OSA patients experience a disappearance of daytime sleepiness symptoms and a significant improvement in their mental state after a single night of CPAP treatment. However, there are relatively few studies on the effects of a single night of CPAP treatment on brain function in OSA patients. Therefore, we hypothesize that a single night of CPAP treatment may also significantly improve brain function in OSA patients.

Source of Research

This study was authored by Yuanfeng Sun, Fei Lei, Lian Luo, Ke Zou, and Xiangdong Tang from the Sleep Medicine Center of the Southwest University Affiliated Huaxi Hospital and was published in the journal “Scientific Reports” in 2023.

Research Content

Research Workflow

The purpose of this study was to investigate the effect of single-night CPAP treatment on spontaneous brain activity in patients with severe OSA and the potential neuropathological mechanisms involved. The study involved 30 severe OSA patients and 19 healthy controls (HC). To assess the spontaneous brain activity of all participants, we used fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) methods.

The specific research workflow is as follows:

1. Subject Recruitment and Basic Information Collection:

   • A total of 30 newly diagnosed, untreated severe OSA male patients and 19 healthy controls (HC) were recruited.
   • Subjects with a history of respiratory, neuropsychiatric, or neurological diseases, or substance or alcohol abuse were excluded.
   • Polysomnography (PSG) and resting-state functional magnetic resonance imaging (rs-fMRI) data were collected at the Southwest University Affiliated Huaxi Hospital.

2. CPAP Treatment:

   • After PSG assessment, single-night (22:30–6:30) CPAP treatment was administered, with the equipment monitoring breathing levels and automatically adjusting pressure.

3. Data Collection and Processing:

   • Structural and functional MRI scans were performed on all participants the next morning between 7:30-8:30 following PSG or CPAP treatment.
   • rs-fMRI data collection parameters included repetition time = 2000ms, echo time = 30ms, flip angle = 90°, slice thickness = 5.0mm, among others.

4. Data Analysis:

   • ReHo and fALFF values were calculated using DPABI software, employing Kendall concordance coefficient and amplitude calculation methods, respectively.
   • Statistical analysis was performed on the generated data, comparing differences before and after treatment and between the treatment group and the healthy control group.

Research Results

Clinical Characteristics

The study found no significant differences between OSA patients and healthy control group in terms of age, educational level, sleep latency, bedtime, total sleep time, and sleep efficiency. However, OSA patients showed significantly higher Epworth Sleepiness Scale (ESS) scores, AHI index, and N1 sleep time, and lower average sleep time oxygen saturation (SaO2), and T90% time during REM and NREM stages.

After a single night of CPAP treatment, OSA patients had significantly increased REM sleep time, N3 sleep time, and SaO2, while AHI and T90% during REM, NREM stages, and total sleep time significantly decreased.

ReHo and fALFF Analysis

Compared to the healthy control group, all patients had significantly reduced ReHo values in the bilateral caudate nucleus regions, and increased fALFF values in the bilateral cerebellum area 8. After a single night of CPAP treatment, ReHo values increased in the bilateral caudate nucleus while ReHo values decreased in the right superior frontal gyrus. fALFF values increased in the left middle frontal gyrus orbital part (frontal_mid_orb_l) and right inferior frontal gyrus orbital part (frontal_inf_orb_r), but decreased in the left superior medial frontal gyrus (frontal_sup_medial_l) and right inferior parietal lobule (parietal_inf_r).

Pearson Correlation Analysis

Based on whole-brain ReHo and fALFF analyses, six regions of interest (ROIs) were identified. The mean ReHo values showed no significant correlation with the polysomnography data. However, the changes in fALFF in the right inferior frontal gyrus orbital part (frontal_inf_orb_r) were positively correlated with changes in REM sleep time (r = 0.437, p = 0.016).

Discussion

This study found that ReHo values in the bilateral caudate nucleus regions of OSA patients were reduced, indicating that local neuronal activity became more disordered over time, and local neuronal connectivity was weakened. The caudate nucleus is a major component of the brain’s learning and memory systems. Previous studies have also shown that untreated OSA patients exhibited structural damage and metabolic changes in the caudate nucleus and hippocampus. This study also showed that ReHo values in the caudate nucleus recovered after one night of CPAP treatment, suggesting that its function was restored.

Additionally, the study found increased fALFF signals in the bilateral cerebellum area 8 in OSA patients, which were significantly negatively correlated with SaO2 and AHI. Related studies have shown that intermittent hypoxia exposure causes dose-dependent damage to neurons in the cerebellum, leading to cerebellar dysfunction. After CPAP treatment, changes were observed in fALFF and ReHo values in multiple brain regions, particularly in the prefrontal cortex, and these changes were related to changes in REM sleep time.

Conclusion

Abnormal changes in fALFF and ReHo were observed in OSA patients before and after single-night CPAP treatment, providing deeper insight into the neural mechanisms of OSA. This study provides important imaging evidence for further research on the neuropathological mechanisms of OSA. Furthermore, the study suggests that single-night CPAP treatment can significantly improve brain function in OSA patients, particularly in the prefrontal cortex, and is associated with the restoration of sleep and cognitive functions.

Research Significance

This study not only reveals the specific brain function impairments caused by OSA but also demonstrates the positive impact of CPAP treatment on brain function recovery. By using advanced fMRI technology and precise fALFF and ReHo analysis methods, the research provides valuable imaging evidence and offers new perspectives for the clinical treatment of OSA and its neural mechanism research. This has significant implications for improving the quality of life of OSA patients, developing new treatment methods, and promoting related basic scientific research.