Alteration in functional-structural connectivities of insula is associated with hypoxic ventilation

Background Hypoxia elicits ventilatory adaptation, and the anterior insula, a hub for interoceptive and exteroceptive integration, is highly vulnerable to hypoxic stress. We hypothesised that it mediates hypoxia-related ventilatory regulation.Methods Thirty-one college students completed 30 days of high altitude exposure. Respiratory function tests and multimodal MRI were conducted immediately at high altitude. Moreover, follow-up MRI scans were performed 7 days, 2 months, and 3 months after the students returned to sea level.Results Pulmonary function (peak expiratory flow (PEF), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC%, maximal mid-expiratory flow (MMF) and minute ventilation (MV)) significantly declined after high altitude exposure. The ALFF increased in the insular cortex, with enhanced FC with the thalamus, motor cortex and postcentral cortex. FC of the left anterior insula with the thalamus was negatively correlated with FEV1 predicted values, while right lateral prefrontal insula-thalamus connectivity was positively correlated with FEV1 and MMF. FC of the anterior insula with the motor cortex and postcentral cortex was negatively correlated with PEF%, FVC and FEV1, respectively. Moreover, fibre pathways linking the anterior insular cortex with the thalamus, motor cortex and postcentral cortex showed increased fibre numbers between these brain regions. Follow-up MRI studies showed that ALFF in the anterior insular cortex was significantly increased immediately after reoxygenation and then recovered to baseline level.Conclusion The anterior insula may serve as a potential hub for integrating hypoxic signals from the thalamus and modulating motor cortex activity, which may contribute to hypoxic ventilation.