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MRI-based volume assessments show no changes in hippocampus, amygdala, thalamus and brainstem subregions in narcolepsy type 1

Juvodden, H. T.; Alnaes, D.; Agartz, I.; Andreassen, O. A.; Server, A.; Thorsby, P. M.; Westlye, L. T.; Knudsen-Heier, S.

2026-03-02 neurology
10.64898/2026.02.21.26345265 medRxiv
Show abstract

Study ObjectivesNarcolepsy type 1 (NT1) is characterized by excessive daytime sleepiness and cataplexy. Previous studies have implicated the amygdala, thalamus, brainstem and hippocampus in the pathophysiology of NT1. We here aimed to examine more detailed subregional case-control differences in MRI-based segmentations of these brain regions to gain deeper insights. MethodsWe obtained 3T MRI brain scans from 54 NT1 patients (39 females, mean age 21.8 {+/-} 11.0 years, 51 with confirmed hypocretin-deficiency and three patients that had not performed this measure) and 114 healthy controls (77 females, mean age 23.2 {+/-} 9.0 years). Automated segmentation of the hippocampus, amygdala, thalamus, and brainstem was performed on T1-weighted MRI data using FreeSurfer. Case-control volume differences were tested using general linear models and permutation testing. The false discovery rate was controlled at 5% with the Benjamini-Hochberg procedure. ResultsThe analysis revealed no significant case-control differences for any of the subregions in the hippocampus, thalamus, amygdala and brainstem after correction for multiple testing. ConclusionsBased on a detailed automated MRI-based segmentation analyses in a relatively large national sample, NT1 patients had no significant changes in any amygdala, thalamus, brainstem or hippocampus subregions compared to controls. In the future large multi-site studies could be performed to achieve sufficient power to detect more subtle group differences.

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