Abnormal Regional Spontaneous Neural Activity and Functional Connectivity in Unmedicated Patients with Narcolepsy Type 1: A Resting-State fMRI Study

Abstract

Background: Previous Resting-state functional magnetic resonance imaging (fMRI) studies have mainly focused on cerebral functional alteration in processing different emotional stimuli in patients with narcolepsy type 1 (NT1), but were short of exploration of characteristic brain activity and its remote interaction patterns. This study aimed to investigate the spontaneous blood oxygen fluctuations at rest and to elucidate the neural mechanisms underlying neuropsychiatric behavior. Method: A total of 18 unmedicated patients with NT1 and matched healthy individuals were recruited in a resting-state fMRI study. Magnetic resonance imaging (MRI) data were first analyzed using fractional low-frequency amplitude of low-frequency fluctuation (fALFF) to detect changes in local neural activity, and regions with group differences were taken as regions of interest (ROIs). Secondly, functional connectivity (FC) analysis was used to explore altered connectivity between ROIs and other areas. Lastly, the relationship between functional brain activity and neuropsychiatric behaviors was analyzed with correlation analysis. Results: fALFF analysis revealed enhanced neural activity in bilateral fusiform gyrus (FFG), right precentral gyrus, and left postcentral gyrus (PoCG) in the NT1 group. The patients indicated reduced activity in the bilateral temporal pole middle temporal gyrus (TPOmid), left caudate nucleus (CAU), left parahippocampus, left precuneus (PCUN), right amygdala, and right anterior cingulate and paracingulate gyri. ESS score was negatively correlated with fALFF in the right FFG. The NT1 group revealed decreased connectivity between left TPOmid and right PoCG, the bilateral middle frontal gyrus, left superior frontal gyrus, medial, and right supramarginal gyrus. Epworth Sleepiness Scale (ESS) was negatively correlated with FC of the left TPOmid with left putamen (PUT) in NT1. Compared with healthy controls (HCs), enhanced FC of the left CAU with right FFG was positively associated with MSLT-SOREMPs in patients. Furthermore, increased FC of the left PCUN with right PoCG was positively correlated with SDS score. Conclusions: We found that multiple functional activities related to the processing of emotional regulation and sensory information processing were abnormal, and some were related to clinical characteristics. fALFF in the left postcentral or right precentral gyrus may be used as a biomarker of narcolepsy, whereas fALFF in the right fusiform and the FC strength of the left temporal pole middle temporal gyrus with the putamen may be clinical indicators to assess the drowsiness severity of narcolepsy.

Assessing resting-state brain functional connectivity in adolescents and young adults with narcolepsy using functional near-infrared spectroscopy

“…In contrast to these findings, however, a substantial corpus of research reports diminished cortical thickness, reduced glucose metabolism, and lower ALFF values in the prefrontal cortex of narcolepsy patients (Joo et al, 2009;Kim et al, 2009;Dang-Vu, 2013;Wada et al, 2019;Cavaliere et al, 2020;Jeon et al, 2020;Wu et al, 2022). These conflicting results may stem from methodological differences in neuroimaging techniques, including changes in data acquisition, preprocessing, analysis, and even patient status during scanning.…”

“…Previous studies based on sMRI, fMRI, DTI, and PET/CT have yielded conflicting results ( Dang-Vu, 2013 ; Cavaliere et al, 2020 ). A large number of structural nuclear magnetic resonance and functional magnetic resonance studies in resting state and task state have proved that the thickness and volume of prefrontal cortex decreased ( Joo et al, 2009 ; Kim et al, 2009 ; Jeon et al, 2020 ), the intensity of functional connection decreased ( Wu et al, 2022 ), and the activity of low frequency amplitude decreased ( Fulong et al, 2018 ), and it was related to clinical features, including cognitive, memory and emotional abnormalities ( Engström et al, 2014 ; Huang et al, 2016 ; Cavaliere et al, 2020 ), which was supported by the hypometabolism of prefrontal cortex shown by PET/CT ( Huang et al, 2018 ). However, the research field is not always consistent.…”