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Abstract Introduction A low arousal threshold (LAT) is a pathophysiological trait of obstructive sleep apnea (OSA) that may be associated with ascending reticular activating system (ARAS)-cortical functional connectivity (FC) changes. We evaluated resting-state FC between the brainstem ARAS nuclei and 105 cortical/subcortical regions in OSA patients with or without a LAT and healthy controls. Methods Twenty-five patients with moderate to severe OSA with an apnea-hypopnea index between 20 and 40/hr (15 with and 10 without a LAT) and 15 age- and sex-matched controls were evaluated. Participants underwent functional magnetic resonance imaging after overnight polysomnography. Three ARAS nuclei—the locus coeruleus (LC), laterodorsal tegmental nucleus (LDTg), and ventral tegmental area (VTA)—associated with OSA in our previous study were used as seeds. Results FC values of the two ARAS nuclei (LC and LDTg) significantly differed among the three groups. FC of the LC with the precuneus was stronger in OSA patients than in controls regardless of the concomitant LAT. FC between the LDTg and the posterior cingulate cortex (PCC) was also stronger in OSA patients regardless of the LAT. Moreover, OSA patients without a LAT showed stronger LDTg-PCC FC than those with a LAT (post hoc p=0.013), and this FC was negatively correlated with the minimum oxygen saturation in OSA patients (r=-0.463, p=0.023). Conclusion The LAT in OSA patients was associated with altered LDTg-PCC FC, which was negatively correlated with the minimum oxygen saturation. This result suggested that cholinergic activity may play a role in the LAT in OSA patients. Support (if any)
Shin et al. (Sat,) studied this question.