17 Introduction and disease severity [80]. Several other studies, however, have failed to find any structural differences in the hypothalamus [82-85] and a recent study reported hypothalamus volume increases in individuals that developed narcolepsy type 1 after Pandemrix vaccination [86]. Other structural findings in narcolepsy type 1 include a consistently reduced volume in frontotemporal regions of the cortex observed across cortical morphometry and thickness [7882, 84, 85, 87-90]. These may be related to typical narcolepsy type 1 complaints, including daytime impairments such as deficits in attention [6, 91-94] and subjective memory complaints [94-96]. These cognitive difficulties could be further explained by a lower volume of the (anterior) hippocampus that has been described by some studies [88, 97-100]. Inconsistent differences within the limbic system in narcolepsy type 1 have also been observed, including reduced volumes of medial prefrontal cortex and anterior cingulate in juveniles and young adults [80, 88] in addition to the amygdala in older adults [97, 101]. These changes have been associated with the frequency and severity of cataplexy as disturbed emotion regulation [97] but could also be related to the altered functional control of the basal amygdala on the brainstem nuclei that normally regulate muscle tone as has been described in rodent studies [102, 103]. Figure 1. Structural T1-weighted magnetic resonance imaging studies investigating central disorders of hypersomnolence. Regions were generally included in case there were at least three independent studies indicating changes within this region in people with a central disorder of hypersomnolence compared to controls. Reported differences could reflect any T1-weighted structural outcome measure, such as volume, cortical thickness, gyrification and/or surface area. The numbers between brackets correspond to the reference numbers of the studies. HC = Healthy controls; NT1 = Narcolepsy type 1; IH = Idiopathic hypersomnia. Figure was created with Biorender. As structural volumetric analyses have resulted in mixed results in narcolepsy type 1, more recent studies moved towards diffusion-weighted 1
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