344 Chapter 11 studies, incorporating a multitude of outcome measures and brain regions in each study, and blinding ourselves for group allocation whenever possible. It is also important to realize how unique the human postmortem dataset of narcolepsy type 1 is that we described in Chapter 6. Globally there is limited narcolepsy type 1 donor tissue available and multiple cases are rarely available in single studies. Besides including larger groups, it is important to also promote clinical diversity in future studies. Our neuroimaging and postmortem studies focussed on narcolepsy type 1, lacking cross-disorder comparisons and largely unknown neural correlates of narcolepsy type 2 and idiopathic hypersomnia. Across studies in section B, multiple individuals with narcolepsy type 1 used medication prior to inclusion which could have influenced brain morphology and/or functioning. In the MRI studies, seven individuals were treatmentnaïve, and five discontinued their stimulants at least two weeks prior to scan acquisition. With this substantial discontinuation period, we aimed to minimize possible effects on brain functioning during the vigilance and active sleep resistance tasks presented in Chapters 7 and 8, while chronic medication effects on white matter structure probably persisted in the results of Chapter 5. Most postmortem donors included in our analyses in Chapter 6 also used medication at time of passing (such as modafinil and sodium oxybate), which could have influenced white matter morphology. Future perspectives Box 2 – Research agenda Section B • Large-scale neuroimaging studies with cross-disorder comparisons • The relationship between brain structure and functioning in narcolepsy type 1 • The need for consistent implementation of objective sleep-wake monitoring • Brain clearance in central disorders of hypersomnolence Large-scale neuroimaging studies with cross-disorder comparisons Compared to many other neurological and psychiatric disorders, neuroimaging in narcolepsy and idiopathic hypersomnia remains in its early stages with few cross-disorder comparisons, limited multimodal perspectives and typically small sample sizes leading to inconsistent findings. Control groups of healthy individuals after sleep deprivation have also been lacking. Both technically advanced studies generating new hypotheses and large-scale international collaborations verifying these results are necessary to overcome these
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