Beyond sleepy: structural and functional changes of the default-mode network in idiopathic hypersomnia

Abstract

Idiopathic hypersomnia (IH) is characterized by excessive daytime sleepiness but, in contrast to narcolepsy, does not involve cataplexy, sleep-onset REM periods, or any consistent hypocretin-1 deficiency. The pathophysiological mechanisms of IH remain unclear. Because of the involvement of the default-mode network (DMN) in alertness and sleep, our aim was to investigate the structural and functional modifications of the DMN in IH. We conducted multimodal magnetic resonance imaging (MRI) in 12 participants with IH and 15 good sleeper controls (mean age ± SD: 32 ± 9.6 years, range 22-53 years, nine males). Self-reported as well as objective measures of daytime sleepiness were collected. Gray matter volume and cortical thickness were analyzed to investigate brain structural differences between good sleepers and IH. Structural covariance and resting-state functional connectivity were analyzed to investigate changes in the DMN. Participants with IH had greater volume and cortical thickness in the precuneus, a posterior hub of the DMN. Cortical thickness in the left medial prefrontal cortex was positively correlated with thickness of the precuneus, and the strength of this correlation was greater in IH. In contrast, functional connectivity at rest was lower within the anterior DMN (medial prefrontal cortex) in IH, and correlated with self-reported daytime sleepiness. The present results show that IH is associated with structural and functional differences in the DMN, in proportion to the severity of daytime sleepiness, suggesting that a disruption of the DMN contributes to the clinical features of IH. Larger volume and thickness in this network might reflect compensatory changes to lower functional connectivity in IH.

Keywords: brain imaging; cortical activation; functional brain imaging; narcolepsy; neuroimaging; sleep and the brain.