MRS study on the correlation between frontal GABA+/Glx ratio and abnormal cognitive function in medication-naive patients with narcolepsy

Objective To compare the GABA+/Glx (glutamate-glutamine) ratio in the prefrontal lobe under non-rapid eye movement sleep between patients with narcolepsy type 1 (NT1) and normal controls and explore the correlation between this difference and abnormal cognitive function, using synchronous electroencephalography-functional magnetic resonance spectroscopy (EEG-fMRS). Methods MRS measurements of GABA+ and Glx concentrations as well as synchronous EEG data were obtained from 26 medication-naive patients with NT1 and 29 sex- and age-matched healthy community volunteers. Cognition was appraised with the Beijing version of the Montreal Cognitive Assessment, and daytime sleepiness was measured using the Epworth Sleepiness Scale. All subjects recorded a 2-week sleep log as well as an overnight polysomnography within 1 week before MR scanning to understand their sleep habits and determine sleep stages. After PSG, they also underwent multiple sleep latency trials. Patient/control group differences in the individual measurements of GABA+ and Glx and the GABA+/Glx ratio and their relationship with cognition were assessed. Results The GABA+/Glx ratio and GABA+ levels of patients with narcolepsy were higher than those of the control group (P＜0.0001 and P=0.0008, respectively). However, there was no significant difference in Glx levels (P=0.6360). The GABA+/Glx ratio negatively correlated with abnormal cognitive function (r=-0.6710, P=0.0002). Moreover, GABA+ levels were inversely proportional to rapid eye movement sleep latency (REML) in patients with narcolepsy (r=-0.5019, P=0.0106). Conclusion The GABA+/Glx ratio in the prefrontal lobe was higher in NT1 patients during N2 sleep than in normal controls, mainly caused by GABA+ levels; this ratio was negatively related to abnormal cognitive function. In addition, GABA+ levels were inversely proportional to REML.