Aberrant Hippocampal Network Connectivity Is Associated With Neurocognitive Dysfunction in Patients With Moderate and Severe Obstructive Sleep Apnea

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.

Aberrant Resting-State Functional Brain Connectivity of Insular Subregions in Obstructive Sleep Apnea

“…Zhang et al (2013) discovered impaired FC of the PreCG in OSA patients and confirmed structural and functional disruptions in the anterior DMN containing the SFG, and speculated these damages may be a probable candidate mechanism for cognitive and emotional disorders in patients with OSA. Furthermore, the increase in FC in the temporal gyrus of OSA patients has been associated with neurocognitive impairment, as affirmed by the study of Zhou et al (2020). The brain areas with abnormal FC in our study overlapped with those previously reported to show structural or functional aberrations in OSA, such as the cerebellum, frontal lobe and temporal lobe, which are distributed in the cognitive control circuit along with the dAI and are responsible for memory, attention, language and executive control (Park et al, 2016a;Caporale et al, 2021).…”

“…For example, Peng et al (2014) found that higher regional homogeneity (ReHo) occurred in the insula of male patients with severe OSA. In addition, altered limbic-striatalcortical functional connectivity was reported in studies of altered hippocampal resting-state functional networks in OSA (Song et al, 2018;Kang et al, 2020;Zhou et al, 2020). Although ReHo and resting-state functional connectivity (FC) are both based on resting-state fMRI, ReHo, a method for analyzing the coherence and similarities of intraregional spontaneous lowfrequency (0.01-0.08 Hz) signal fluctuations was used to detect unpredicted hemodynamic responses (Zang et al, 2004).…”

Frequency‑Specific Regional Homogeneity Alterations and Cognitive Function in Obstructive Sleep Apnea Before and After Short-Term Continuous Positive Airway Pressure Treatment

“… 48 It has been reported that FC abnormalities in the right hippocampus and right STG and MTG in OSA are negatively correlated with performance of information processing speed, which may probably contribute to the development of cognitive dysfunction. 38 Our previous study found an increase in rs-FC between the left IFG and bilateral ventrolateral amygdala in OSA patients, reflecting the potential adaptive compensation mechanism for the decline in emotion functions. 49 A study reported decreased mean diffusivity and increased functional anisotropy in the temporal lobes and fusiform gyrus, and increased CBF in the ITG was found in OSA with six weeks of CPAP treatment, suggesting that CPAP therapy can recover OSA-induced brain injury.…”

“… 37 One functional connectivity study demonstrated decreased functional connectivity between the left cerebellum and hippocampus. 38 Park et al found that OSA showed cerebellar network integration and cerebrocerebellar connectivity was impaired in OSA patients, which may participate in cognitive decline. 39 The cerebellum was susceptible to hypoxia or ischaemia.…”

You Cannot Hit Snooze on OSA: Sequelae of Pediatric Obstructive Sleep Apnea

“…Impaired attention is found in OSA children. Studies assessing polysomnograms and MRIs suggest that attention and vigilance are prominent neurocognitive functions that are impaired in children with OSA [ 65 ]. There are three components of attention, each of which can be compromised in patients with OSA.…”