346 Chapter 11 have pledged inclusion of 1000 individuals with narcolepsy type 1, 220 with narcolepsy type 2, 230 with idiopathic hypersomnia and 800 healthy controls. The analysis container for the first T1-weighted structural analyses has been developed within our team and will soon be distributed to participating sites. NICHY provides the global framework for international collaboration on neuroimaging in central disorders of hypersomnolence and in future projects we aim to extend to DWI-derived structural and fMRI connectivity measures. The relationship between brain structure and functioning in narcolepsy type 1 The exact relationship between the structural and functional differences observed in narcolepsy type 1 remains a chicken-or-egg debate as most studies included individuals with relatively long disease durations. Understanding whether structural distinctions directly contribute to altered brain activity or if they are an outcome of prolonged symptomatology remains ambiguous. A plausible perspective is that the observed structural effects are intricately tied to the chronic symptoms associated with hypocretin deficiency. Future studies should aim to include samples closer to disease onset to uncover this. Apart from the hypothalamus-seeded tractography, most of our MRI analyses shown in Chapters 5, 7 and 8 compared outcome measures from single regions between groups to identify localized differences in brain structure or activity. Graph theory approaches have recently garnered increased interest in neuroimaging studies, as the resulting structural and functional connectivity measures enable assessment of larger brain networks [444, 445]. Graph measures hereby provide holistic ways to conceptualize and understand what actually happens to the global status of the brain in individuals with central disorders of hypersomnolence, beyond less understood local increases or decreases in structure or functioning. Future investigations on our datasets or external samples should implement multimodal whole brain connectivity measures to gain a more comprehensive understanding of the intricate relationship between brain structure and functioning. The need for consistent implementation of objective sleep-wake monitoring We have been among the first to implement synchronous EEG-fMRI measurements of individuals with narcolepsy type 1 described in Chapter 8. Combining these two powerful neuroimaging techniques forms an important next step for this field as it allows for great spatial and temporal resolution that is particularly suitable for sleep-wake analyses. It provides the opportunity to
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