Lag Analysis of Fast fMRI Reveals Delayed Information Flow Between the Default Mode and Other Networks in Narcolepsy

Narcolepsy is a chronic neurological disease characterized by dysfunction of the hypocretin system in brain causing disruption in the wake-promoting system. In addition to sleep attacks and cataplexy, patients with narcolepsy commonly report cognitive symptoms while objective deficits in sustained attention and executive function have been observed. Prior resting-state functional magnetic resonance imaging (fMRI) studies in narcolepsy have reported decreased inter/intranetwork connectivity regarding the default mode network (DMN). Recently developed fast fMRI data acquisition allows more precise detection of brain signal propagation with a novel dynamic lag analysis. In this study, we used fast fMRI data to analyze dynamics of inter resting-state network (RSN) information signaling between narcolepsy type 1 patients (NT1, n = 23) and age- and sex-matched healthy controls (HC, n = 23). We investigated dynamic connectivity properties between positive and negative peaks and, furthermore, their anticorrelative (pos-neg) counterparts. The lag distributions were significantly (P < 0.005, familywise error rate corrected) altered in 24 RSN pairs in NT1. The DMN was involved in 83% of the altered RSN pairs. We conclude that narcolepsy type 1 is characterized with delayed and monotonic inter-RSN information flow especially involving anticorrelations, which are known to be characteristic behavior of the DMN regarding neurocognition.