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

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.

Altered Regional Cerebral Blood Flow in Idiopathic Hypersomnia.

Study Objectives: Idiopathic hypersomnia is characterized by excessive daytime sleepiness, despite normal or long sleep time. Its pathophysiological mechanisms remain unclear. This pilot study aims at characterizing the neural correlates of idiopathic hypersomnia using single photon emission computed tomography. Methods: Thirteen participants with idiopathic hypersomnia and 16 healthy controls were scanned during resting wakefulness using a high-resolution single photon emission computed tomography scanner with 99mTc-ethyl cysteinate dimer to assess cerebral blood flow. The main analysis compared regional cerebral blood flow distribution between the two groups. Exploratory correlations between regional cerebral blood flow and clinical characteristics evaluated the functional correlates of those brain perfusion patterns. Significance was set at p < .05 after correction for multiple comparisons. Results: Participants with idiopathic hypersomnia showed regional cerebral blood flow decreases in medial prefrontal cortex and posterior cingulate cortex and putamen, as well as increases in amygdala and temporo-occipital cortices. Lower regional cerebral blood flow in the medial prefrontal cortex was associated with higher daytime sleepiness. Conclusions: These preliminary findings suggest that idiopathic hypersomnia is characterized by functional alterations in brain areas involved in the modulation of vigilance states, which may contribute to the daytime symptoms of this condition. The distribution of regional cerebral blood flow changes was reminiscent of the patterns associated with normal non-rapid-eye-movement sleep, suggesting the possible presence of incomplete sleep-wake transitions. These abnormalities were strikingly distinct from those induced by acute sleep deprivation, suggesting that the patterns seen here might reflect a trait associated with idiopathic hypersomnia rather than a non-specific state of sleepiness.