147 White Matter Connectivity in Narcolepsy Type 1 Figure 4. Connectivity of the hypothalamus of one subject. In (A) the overall connectivity of the hypothalamus by itself is shown. (B-D) represent components of (A), connecting the hypothalamus with the regions-of-interest. Significantly different fractional anisotropy values were plotted as mean with the corresponding 95% confidence interval for both patients (P) and controls (C). Discussion Microstructural WM properties were significantly abnormal in people with narcolepsy type 1 in the three methodologies used. Whole-brain lower FA and higher RD – excluding the cerebellum – were seen in people with narcolepsy type 1 within functional networks such as the sleep-wake regulation, limbic and reward system and corticospinal tract (I). In patients mean lower FA and higher RD in the left ventral diencephalon and lower AD in the midbrain were found (II). Patients’ tracts connecting the left hypothalamus with the midbrain showed lower FA (III). This study suggests a heretofore underestimated modulatory effect of hypocretin deficiency on microstructural white matter composition in patients with narcolepsy type 1. Tract-based spatial statistics (I) The widespread microstructural WM disruptions we found (I), are generally in keeping with a previous large-scale TBSS study [105] which found brain-wide significantly lower FA and indifferent MD in drug-naïve patients with narcolepsy type 1, including the corpus callosum, midbrain and bilateral cingulate gyrus, thalamus, internal capsule. Higher RD was also reported in the midbrain and bilateral thalamus and lower AD in the corpus callosum. Discrepancies with this study in AD and RD differences most likely result from their lower 5
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