ABSTRACT Background Narcolepsy Type 1 (NT1) results from loss of hypothalamic orexin neurons, leading to unstable sleep–wake transitions. However, how this manifests as dynamic whole‐brain functional state instability remains poorly characterized. Methods We applied Hidden Markov Modeling (HMM) to resting‐state functional magnetic resonance imaging (fMRI) data from 30 patients with NT1 and 30 age‐ and sex‐matched healthy controls to identify recurrent brain states, quantify their fractional occupancy (FO), and examine associations with clinical symptoms—specifically excessive daytime sleepiness (Epworth Sleepiness Scale, ESS) and hallucinations. Results Five distinct dynamic brain states were identified. Compared to controls, NT1 patients showed significantly reduced FO in State 1 (thalamocortical arousal/sensory gating; p FDR < 0.001) and elevated FO in State 4 (basal ganglia–limbic–sensorimotor integration; p FDR < 0.001) and State 5 (reward‐introspection; p FDR = 0.036). Notably, within the NT1 group, patients with hallucinations exhibited higher FO in State 1 than those without ( p FDR = 0.042), suggesting aberrant recruitment of this state during sleep–wake transitions. Additionally, State 4 FO showed a moderate positive correlation with ESS scores (Spearman's ρ = 0.38, p FDR = 0.078). Conclusions NT1 is associated with reduced stability of a thalamocortical alertness state and increased expression of REM‐like limbic‐subcortical network configurations. State 1 occupancy is relatively elevated in patients with hallucinations, while State 4 shows a positive association with excessive daytime sleepiness and features of REM dissociation. These findings support a dynamic, whole‐brain systems‐level framework for understanding symptom heterogeneity in NT1.
Li et al. (Tue,) studied this question.
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