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Project","award":["YC2021-B049"],"award-info":[{"award-number":["YC2021-B049"]}]},{"name":"Jiangxi Province Postgraduate Innovation Special Fund","award":["31860293"],"award-info":[{"award-number":["31860293"]}]},{"name":"Jiangxi Province Postgraduate Innovation Special Fund","award":["82160227"],"award-info":[{"award-number":["82160227"]}]},{"name":"Jiangxi Province Postgraduate Innovation Special Fund","award":["20192BAB205047"],"award-info":[{"award-number":["20192BAB205047"]}]},{"name":"Jiangxi Province Postgraduate Innovation Special Fund","award":["202210645"],"award-info":[{"award-number":["202210645"]}]},{"name":"Jiangxi Province Postgraduate Innovation Special Fund","award":["GJJ210125"],"award-info":[{"award-number":["GJJ210125"]}]},{"name":"Jiangxi Province Postgraduate Innovation Special Fund","award":["YC2021-B049"],"award-info":[{"award-number":["YC2021-B049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijerph192315482","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T02:10:54Z","timestamp":1669169454000},"page":"15482","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Abnormal Regional Spontaneous Neural Activity and Functional Connectivity in Unmedicated Patients with Narcolepsy Type 1: A Resting-State fMRI Study"],"prefix":"10.3390","volume":"19","author":[{"given":"Lanxiang","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Imaging Department, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suheng","family":"Xie","sequence":"additional","affiliation":[{"name":"Imaging Department, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Emerging therapeutic targets for narcolepsy","volume":"20","author":"Vringer","year":"2021","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13387","DOI":"10.1111\/jsr.13387","article-title":"European guideline and expert statements on the management of narcolepsy in adults and children","volume":"30","author":"Bassetti","year":"2021","journal-title":"J. Sleep Res."},{"key":"ref_3","first-page":"103","article-title":"[Narcolepsy in adults: Definition, etiology and treatment]","volume":"89","author":"Malter","year":"2021","journal-title":"Fortschr. Neurol. Psychiatr."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Morse, A.M. (2019). Narcolepsy in Children and Adults: A Guide to Improved Recognition, Diagnosis and Management. Med. Sci., 7.","DOI":"10.3390\/medsci7120106"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/joim.13406","article-title":"Hypocretins (orexins): The ultimate translational neuropeptides","volume":"291","author":"Jacobson","year":"2022","journal-title":"J. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101546","DOI":"10.1016\/j.smrv.2021.101546","article-title":"Neurobiology of cataplexy","volume":"60","author":"Seifinejad","year":"2021","journal-title":"Sleep Med. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3389\/fnbeh.2013.00028","article-title":"Role of orexin in modulating arousal, feeding, and motivation","volume":"7","author":"Tsujino","year":"2013","journal-title":"Front. Behav. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101875","DOI":"10.1016\/j.nicl.2019.101875","article-title":"Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin","volume":"23","author":"Drissi","year":"2019","journal-title":"Neuroimage Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.sleep.2018.08.022","article-title":"Differences in diffusion tensor imaging changes between narcolepsy with and without cataplexy","volume":"52","author":"Tezer","year":"2018","journal-title":"Sleep Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1136\/jnnp.2009.175786","article-title":"A brain PET study in patients with narcolepsy-cataplexy","volume":"81","author":"Dauvilliers","year":"2010","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"zsz082","DOI":"10.1093\/sleep\/zsz082","article-title":"Hypocretin-deficient narcolepsy patients have abnormal brain activation during humor processing","volume":"42","author":"Juvodden","year":"2019","journal-title":"Sleep"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"16391","DOI":"10.1038\/s41598-018-34647-6","article-title":"Enhanced food-related responses in the ventral medial prefrontal cortex in narcolepsy type 1","volume":"8","author":"Janssen","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.clinimag.2020.04.004","article-title":"Current methods and new directions in resting state fMRI","volume":"65","author":"Yang","year":"2020","journal-title":"Clin. Imaging"},{"key":"ref_14","first-page":"378","article-title":"[Potential Clinical Applications of Resting-State-FMRI in Neurology]","volume":"158","author":"Paz","year":"2019","journal-title":"Harefuah"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s12264-018-0307-6","article-title":"Independent Component Analysis and Graph Theoretical Analysis in Patients with Narcolepsy","volume":"35","author":"Xiao","year":"2019","journal-title":"Neurosci. Bull."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102748","DOI":"10.1016\/j.nicl.2021.102748","article-title":"Hypothalamus and amygdala functional connectivity at rest in narcolepsy type 1","volume":"31","author":"Ballotta","year":"2021","journal-title":"Neuroimage Clin."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.braindev.2006.07.002","article-title":"Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI","volume":"29","author":"Zang","year":"2007","journal-title":"Brain Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.neuroimage.2014.09.038","article-title":"Stability of low-frequency fluctuation amplitudes in prolonged resting-state fMRI","volume":"103","author":"Woletz","year":"2014","journal-title":"Neuroimage"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.nic.2019.09.012","article-title":"Resting-State Functional Connectivity: Signal Origins and Analytic Methods","volume":"30","author":"Chen","year":"2020","journal-title":"Neuroimaging Clin. N. Am."},{"key":"ref_20","unstructured":"American Academy of Sleep Medicine (2014). International Classification of Sleep Disorders, American Academy of Sleep Medicine. [3rd ed.]."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11583","DOI":"10.1523\/JNEUROSCI.0840-15.2015","article-title":"The Brain Correlates of Laugh and Cataplexy in Childhood Narcolepsy","volume":"35","author":"Meletti","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12993-018-0151-x","article-title":"Narcolepsy and emotional experience: A review of the literature","volume":"14","author":"Schiappa","year":"2018","journal-title":"Behav. Brain Funct."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.jsmc.2017.03.021","article-title":"Neuroimaging of Narcolepsy and Kleine-Levin Syndrome","volume":"12","author":"Hong","year":"2017","journal-title":"Sleep Med. Clin."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.sleep.2015.11.023","article-title":"Brain imaging and cognition in young narcoleptic patients","volume":"24","author":"Huang","year":"2016","journal-title":"Sleep Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1007\/s11682-015-9450-0","article-title":"Morphological alterations in amygdalo-hippocampal substructures in narcolepsy patients with cataplexy","volume":"10","author":"Kim","year":"2016","journal-title":"Brain Imaging Behav."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.sleep.2011.09.017","article-title":"Hippocampal volume and memory in narcoleptics with cataplexy","volume":"13","author":"Joo","year":"2012","journal-title":"Sleep Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1111\/bph.14626","article-title":"Modafinil protects hippocampal neurons by suppressing excessive autophagy and apoptosis in mice with sleep deprivation","volume":"176","author":"Cao","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.neulet.2007.04.085","article-title":"Modafinil-induced hippocampal activation in narcolepsy","volume":"422","author":"Kim","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5275","DOI":"10.1523\/JNEUROSCI.3200-12.2013","article-title":"Hypocretin\/orexin neurons contribute to hippocampus-dependent social memory and synaptic plasticity in mice","volume":"33","author":"Yang","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.tics.2005.10.011","article-title":"How brains beware: Neural mechanisms of emotional attention","volume":"9","author":"Vuilleumier","year":"2005","journal-title":"Trends Cogn. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1126\/science.abl6618","article-title":"Rapid eye movement sleep is initiated by basolateral amygdala dopamine signaling in mice","volume":"375","author":"Hasegawa","year":"2022","journal-title":"Science"},{"key":"ref_32","first-page":"652","article-title":"Volume of the amygdala is reduced in patients with narcolepsy\u2014A structural MRI study","volume":"32","author":"Brabec","year":"2011","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0306-4522(02)00089-1","article-title":"Cataplexy-related neurons in the amygdala of the narcoleptic dog","volume":"112","author":"Gulyani","year":"2002","journal-title":"Neuroscience"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10243","DOI":"10.1523\/JNEUROSCI.1004-10.2010","article-title":"Intrinsic connectivity networks, alpha oscillations, and tonic alertness: A simultaneous electroencephalography\/functional magnetic resonance imaging study","volume":"30","author":"Sadaghiani","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1093\/sleep\/33.10.1295","article-title":"Dopaminergic regulation of sleep and cataplexy in a murine model of narcolepsy","volume":"33","author":"Burgess","year":"2010","journal-title":"Sleep"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.sleep.2012.02.013","article-title":"DTI reveals hypothalamic and brainstem white matter lesions in patients with idiopathic narcolepsy","volume":"13","author":"Menzler","year":"2012","journal-title":"Sleep Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S0306-4522(00)00239-6","article-title":"Implication of dopaminergic mechanisms in the wake-promoting effects of amphetamine: A study of D- and L-derivatives in canine narcolepsy","volume":"99","author":"Kanbayashi","year":"2000","journal-title":"Neuroscience"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"936","DOI":"10.3389\/fneur.2018.00936","article-title":"Recursive Partitioning Analysis of Fractional Low-Frequency Fluctuations in Narcolepsy With Cataplexy","volume":"9","author":"Xiao","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_39","first-page":"344","article-title":"Regional brain metabolism differentiates narcolepsy type 1 and idiopathic hypersomniar","volume":"8","author":"Trotti","year":"2021","journal-title":"Sleep"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Nakamura, M., Nishida, S., Hayashida, K., Ueki, Y., Dauvilliers, Y., and Inoue, Y. (2013). Differences in brain morphological findings between narcolepsy with and without cataplexy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081059"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/ana.21825","article-title":"Abnormal activity in reward brain circuits in human narcolepsy with cataplexy","volume":"67","author":"Ponz","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s00415-005-0598-1","article-title":"Functional involvement of cerebral cortex in human narcolepsy","volume":"252","author":"Oliviero","year":"2005","journal-title":"J. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3389\/fneur.2017.00350","article-title":"[18F]Fludeoxyglucose-Positron Emission Tomography Evidence for Cerebral Hypermetabolism in the Awake State in Narcolepsy and Idiopathic Hypersomnia","volume":"8","author":"Dauvilliers","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s11060-020-03656-9","article-title":"Awake surgery for right frontal lobe glioma can preserve visuospatial cognition and spatial working memory","volume":"151","author":"Nakada","year":"2021","journal-title":"J. Neurooncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.5665\/SLEEP.1278","article-title":"Analysis of cortical thickness in narcolepsy patients with cataplexy","volume":"34","author":"Joo","year":"2011","journal-title":"Sleep"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.sleep.2005.03.015","article-title":"Voxel-based morphometry in narcolepsy","volume":"6","author":"Brenneis","year":"2005","journal-title":"Sleep Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"345","DOI":"10.5665\/sleep.1692","article-title":"White and gray matter abnormalities in narcolepsy with cataplexy","volume":"35","author":"Scherfler","year":"2012","journal-title":"Sleep"}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/23\/15482\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:24:32Z","timestamp":1760145872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/23\/15482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,22]]},"references-count":47,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijerph192315482"],"URL":"https:\/\/doi.org\/10.3390\/ijerph192315482","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,22]]}}}