Morphological and Age-Related Changes in the Narcolepsy Brain.

Morphological changes in the cortex of narcolepsy patients were investigated by surface-based morphometry analysis in this study. Fifty-one type 1 narcolepsy patients and 60 demographically group-matched healthy controls provided resting-state functional and high-resolution 3T anatomical magnetic resonance imaging scans. Vertex-level cortical thickness (CT), gyrification, and voxel-wise functional connectivity were calculated. Adolescent narcolepsy patients showed decreased CT in bilateral frontal cortex and left precuneus. Adolescent narcolepsy demonstrated increased gyrification in left occipital lobe, left precuneus, and right fusiform but decreased gyrification in left postcentral gyrus, whereas adult narcolepsy exhibited increased gyrification in left temporal lobe and right frontal cortex. Furthermore, sleepiness severity was associated with altered CT and gyrification. Increased gyrification was associated with reduced long-range functional connectivity. In adolescent patients, those with more severe sleepiness showed increased right postcentral gyrification. Decreased frontal and occipital gyrification was found in cases with hallucination. In adult patients, a wide range of regions showed reduced gyrification in those with adolescence-onset compared adult-onset narcolepsy patients. Particularly the frontal lobes showed altered brain morphology, being a thinner cortex and more gyri. The impact of narcolepsy on age-related brain morphological changes may remain from adolescence to young adulthood, and it was especially exacerbated in adolescence.

Resting-state brain network topological properties and the correlation with neuropsychological assessment in adolescent narcolepsy.

STUDY OBJECTIVES: To evaluate functional connectivity and topological properties of brain networks, and to investigate the association between brain topological properties and neuropsychiatric behaviors in adolescent narcolepsy. METHODS: Resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessment were applied in 26 adolescent narcolepsy patients and 30 healthy controls. fMRI data were analyzed in three ways: group independent component analysis and a graph theoretical method were applied to evaluate topological properties within the whole brain. Lastly, network-based statistics was utilized for group comparisons in region-to-region connectivity. The relationship between topological properties and neuropsychiatric behaviors was analyzed with correlation analyses. RESULTS: In addition to sleepiness, depressive symptoms and impulsivity were detected in adolescent narcolepsy. In adolescent narcolepsy, functional connectivity was decreased between regions of the limbic system and the default mode network (DMN), and increased in the visual network. Adolescent narcolepsy patients exhibited disrupted small-world network properties. Regional alterations in the caudate nucleus (CAU) and posterior cingulate gyrus were associated with subjective sleepiness and regional alterations in the CAU and inferior occipital gyrus were associated with impulsiveness. Remodeling within the salience network and the DMN was associated with sleepiness, depressive feelings, and impulsive behaviors in narcolepsy. CONCLUSIONS: Alterations in brain connectivity and regional topological properties in narcoleptic adolescents were associated with their sleepiness, depressive feelings, and impulsive behaviors.

Recursive Partitioning Analysis of Fractional Low-Frequency Fluctuations in Narcolepsy With Cataplexy.

Objective: To identify narcolepsy related regional brain activity alterations compared with matched healthy controls. To determine whether these changes can be used to distinguish narcolepsy from healthy controls by recursive partitioning analysis (RPA) and receiver operating characteristic (ROC) curve analysis. Method: Fifty-one narcolepsy with cataplexy patients (26 adults and 25 juveniles) and sixty matched heathy controls (30 adults and 30 juveniles) were recruited. All subjects underwent a resting-state functional magnetic resonance imaging scan. Fractional low-frequency fluctuations (fALFF) was used to investigate narcolepsy induced regional brain activity alterations among adult and juveniles, respectively. Recursive partitioning analysis and Receiver operating curve analysis was used to seek the ability of fALFF values within brain regions in distinguishing narcolepsy from healthy controls. Results: Compared with healthy controls, both adult and juvenile narcolepsy had lower fALFF values in bilateral medial superior frontal gyrus, bilateral inferior parietal lobule and supra-marginal gyrus. Compared with healthy controls, both adult and juvenile narcolepsy had higher fALFF values in bilateral sensorimotor cortex and middle temporal gyrus. Also juvenile narcolepsy had higher fALFF in right putamen and right thalamus compared with healthy controls. Based on RPA and ROC curve analysis, in adult participants, fALFF differences in right medial superior frontal gyrus can discriminate narcolepsy from healthy controls with high degree of sensitivity (100%) and specificity (88.9%). In juvenile participants, fALFF differences in left superior frontal gyrus can discriminate narcolepsy from healthy controls with moderate degree of sensitivity (57.1%) and specificity (88.9%). Conclusion: Compared with healthy controls, both the adult and juvenile narcolepsy showed overlap brain regions in fALFF differences after case-control comparison. Furthermore, we propose that fALFF value can be a helpful imaging biomarker in distinguishing narcolepsy from healthy controls among both adults and juveniles.