Dynamic Brain State Alterations in Narcolepsy: A Hidden Markov Model Approach to Thalamocortical Instability and Symptom‐Specific Neural Correlates

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: = 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.