Attention and inhibition deficits in narcolepsy type 1: behavioral and electrophysiological markers

Cognitive impairments in narcolepsy type 1 (NT1) significantly compromise daily functioning, but their neural mechanisms remain unclear. This study employed multimodal electroencephalography (EEG) analyses to investigate electrophysiological substrates of attention and inhibition deficits in NT1 and their association with clinical characteristics, particularly orexin deficiency. High-density EEG recordings were acquired during a Go/NoGo task from 39 NT1 patients and 41 age-/sex-matched healthy controls. Behavioral analyses revealed that compared to controls, NT1 patients exhibited significantly prolonged reaction times and increased errors across both Go and NoGo conditions. Electrophysiological analyses demonstrated that NT1 patients showed: (1) delayed Go-P3 latencies, meaning impaired response preparation; (2) reduced NoGo-P3 amplitudes, reflecting deficient inhibitory control; and (3) attenuated theta-band power and inter-trial phase consistency across conditions. Notably, decreased theta-band power correlated with both lower orexin levels and slower reaction times. This suggests that altered theta-band activity may represent a core neural substrate linking the underlying pathophysiology (i.e., orexin deficiency) to its clinical cognitive manifestations. Thus, we propose theta-band oscillations as a potential clinically translatable biomarker for NT1-related cognitive deficits, with promising implications for objective monitoring of disease progression and developing EEG-targeted neuromodulation therapies.