{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:46:27Z","timestamp":1784958387026,"version":"3.55.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Recently, many studies have shown that low vitamin D (VD) levels may be related to an increased risk of Parkinson\u2019s disease (PD), but the underlying mechanisms remain unclear.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> To explore the relationship between PD and VD levels, as well as to analyze the effects of VD on spontaneous brain activity and explore the possible mechanism of its involvement in PD risk.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In a cross-sectional study, we quantified the difference in VD levels between 330 PD patients and 209 healthy controls (HC) to explore the correlation between VD and PD risk. We also acquired resting-state Functional Magnetic Resonance Imaging (rs-fMRI) data from 46 PD patients and 21 HC. The PD patients were divided into three groups according to 25(OH)D levels: PD patients with VD deficiency (PD + VDD), PD patients with VD insufficiency (PD + VDI), and PD patients with normal VD (PD + NVD). The effect of VD status on spontaneous neuronal activity in the whole brain was analyzed by measuring the fraction amplitude of low-frequency fluctuation (fALFF).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Compared with HC, the PD patients had lower serum 25(OH)D levels (23.60 \u00b1 7.27 vs. 25.60 \u00b1 5.78, <jats:italic>P<\/jats:italic> &amp;lt; 0.001). The 25(OH)D level may have a potential dose-dependent effect on the risk of PD (<jats:italic>P<\/jats:italic><jats:sub><jats:italic>trend<\/jats:italic><\/jats:sub> = 0.007). A high risk of PD was associated with VD deficiency [25(OH)D &amp;lt; 20 ng\/mL, OR = 2.319], and the lowest quartile of 25(OH)D concentration was associated with a high risk of PD (OR = 1.941). In the rs-fMRI study, PD + VDD patients had wider brain regions with altered fALFF than other PD groups when compared with the corresponding HC groups. Both PD + VDD and PD + VDI showed higher fALFF in the cuneus, left precuneus, calcarine cortex and right lingual, as well as lower fALFF in the left middle temporal gyrus. PD + VDD patients also showed higher fALFF in the left superior, middle and inferior frontal gyri, as well as the left precentral gyrus than HC. Among PD patients, there was only a statistically significant difference in fALFF between the PD + VDD and PD + NVD groups. Compared with the PD + NVD group, PD + VDD patients exhibited higher fALFF in the left precentral and left postcentral gyrus, as well as the left inferior parietal lobule.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> These results demonstrate that PD patients had lower serum VD levels than HC, and VD may have a potential dose-dependent effect on PD risk. Lower serum VD levels can affect the spontaneous neuronal activity of default-mode network (DMN) and visual pathway neurons in PD patients, providing a possible mechanism for its effect on PD risk.<\/jats:p>","DOI":"10.3389\/fnagi.2021.763947","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T08:08:31Z","timestamp":1639987711000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Assessing the Effects of Vitamin D on Neural Network Function in Patients With Parkinson\u2019s Disease by Measuring the Fraction Amplitude of Low-Frequency Fluctuation"],"prefix":"10.3389","volume":"13","author":[{"given":"Lingling","family":"Lv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hainan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuling","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinke","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qile","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlian","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqian","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieqiong","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beisha","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1002\/mds.20362","article-title":"Challenging conventional wisdom: the etiologic role of dopamine oxidative stress in Parkinson\u2019s disease.","volume":"20","author":"Ahlskog","year":"2005","journal-title":"Mov. Disord."},{"key":"B2","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.neuron.2010.02.005","article-title":"Functional-anatomic fractionation of the brain\u2019s default network.","volume":"65","author":"Andrews-Hanna","year":"2010","journal-title":"Neuron"},{"key":"B3","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and treatment of Parkinson disease.","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1016\/s1474-4422(16)30230-7","article-title":"The epidemiology of Parkinson\u2019s disease: risk factors and prevention.","volume":"15","author":"Ascherio","year":"2016","journal-title":"Lancet Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/jnr.23318","article-title":"5-S-cysteinyldopamine neurotoxicity: influence on the expression of alpha-synuclein and ERp57 in cellular and animal models of Parkinson\u2019s disease.","volume":"92","author":"Aureli","year":"2014","journal-title":"J. Neurosci. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1212\/WNL.0b013e31826c197f","article-title":"Vitamin D, cognition, and dementia: a systematic review and meta-analysis.","volume":"79","author":"Balion","year":"2012","journal-title":"Neurology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b3692","article-title":"Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials.","volume":"339","author":"Bischoff-Ferrari","year":"2009","journal-title":"BMJ"},{"key":"B8","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.cca.2019.07.022","article-title":"Standardized measurement of circulating vitamin D [25(OH)D] and its putative role as a serum biomarker in Alzheimer\u2019s disease and Parkinson\u2019s disease.","volume":"497","author":"Bivona","year":"","journal-title":"Clin. Chim. Acta"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/medicina55070341","article-title":"Non-Skeletal activities of vitamin D: from physiology to brain pathology.","volume":"55","author":"Bivona","year":"","journal-title":"Medicina (Kaunas)"},{"key":"B10","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1080\/01616412.2019.1622872","article-title":"Vitamin D and the nervous system.","volume":"41","author":"Bivona","year":"","journal-title":"Neurol Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s11481-016-9720-7","article-title":"Vitamin D treatment attenuates neuroinflammation and dopaminergic neurodegeneration in an animal model of Parkinson\u2019s disease, shifting M1 to M2 microglia responses.","volume":"12","author":"Calvello","year":"2017","journal-title":"J. Neuroimmune Pharmacol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.jsbmb.2016.04.006","article-title":"Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor.","volume":"163","author":"Claro da Silva","year":"2016","journal-title":"J. Steroid. Biochem. Mol. Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.mce.2017.05.035","article-title":"Vitamin D and the brain: genomic and non-genomic actions.","volume":"453","author":"Cui","year":"2017","journal-title":"Mol. Cell Endocrinol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1212\/wnl.0b013e3182a95818","article-title":"Unrecognized vitamin D3 deficiency is common in Parkinson disease: harvard biomarker study.","volume":"81","author":"Ding","year":"2013","journal-title":"Neurology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1001\/archneur.65.10.1348","article-title":"Prevalence of vitamin D insufficiency in patients with Parkinson disease and Alzheimer disease.","volume":"65","author":"Evatt","year":"2008","journal-title":"Arch. Neurol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1001\/archneurol.2011.30","article-title":"High prevalence of hypovitaminosis D status in patients with early Parkinson disease.","volume":"68","author":"Evatt","year":"2011","journal-title":"Arch. Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"S265","DOI":"10.1016\/j.psyneuen.2009.05.023","article-title":"Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases.","volume":"34","author":"Fernandes de Abreu","year":"2009","journal-title":"Psychoneuroendocrinology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1046\/j.1471-4159.1999.0730859.x","article-title":"1,25-dihydroxyvitamin D3 regulates the synthesis of gamma-glutamyl transpeptidase and glutathione levels in rat primary astrocytes.","volume":"73","author":"Garcion","year":"1999","journal-title":"J. Neurochem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.pneurobio.2013.10.004","article-title":"Autophagy and apoptosis dysfunction in neurodegenerative disorders.","volume":"112","author":"Ghavami","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1016\/j.freeradbiomed.2006.06.016","article-title":"Cooperative activity of Ref-1\/APE and ERp57 in reductive activation of transcription factors.","volume":"41","author":"Grillo","year":"2006","journal-title":"Free Radic Biol. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1146\/annurev-nutr-071813-105557","article-title":"Vitamin D as a neurosteroid affecting the developing and adult brain.","volume":"34","author":"Groves","year":"2014","journal-title":"Annu. Rev. Nutr."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.","volume":"96","author":"Holick","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B23","doi-asserted-by":"publisher","first-page":"6048","DOI":"10.3390\/nu6126048","article-title":"Neurochemical effects of chronic administration of calcitriol in rats.","volume":"6","author":"Jiang","year":"2014","journal-title":"Nutrients"},{"key":"B24","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/s0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease.","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"B25","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1001\/archneurol.2010.120","article-title":"Serum vitamin D and the risk of Parkinson disease.","volume":"67","author":"Knekt","year":"2010","journal-title":"Arch. Neurol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1002\/mds.27069","article-title":"No clear support for a role for vitamin D in Parkinson\u2019s disease: a Mendelian randomization study.","volume":"32","author":"Larsson","year":"2017","journal-title":"Mov. Disord."},{"key":"B27","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1097\/WNR.0000000000000401","article-title":"Biochemical protective effect of 1,25-dihydroxyvitamin D3 through autophagy induction in the MPTP mouse model of Parkinson\u2019s disease.","volume":"26","author":"Li","year":"2015","journal-title":"Neuroreport"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1266-6","article-title":"Vitamin D protects dopaminergic neurons against neuroinflammation and oxidative stress in hemiparkinsonian rats.","volume":"15","author":"Lima","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"B29","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s10072-013-1539-x","article-title":"Serum 25-hydroxyvitamin D predicts severity in Parkinson\u2019s disease patients.","volume":"35","author":"Liu","year":"2013","journal-title":"Neurol. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1289\/ehp.7573","article-title":"The role of early life environmental risk factors in Parkinson disease: what is the evidence?","volume":"113","author":"Logroscino","year":"2005","journal-title":"Environ. Health Perspect."},{"key":"B31","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.parkreldis.2016.09.012","article-title":"Altered functional connectivity in the default mode network is associated with cognitive impairment and brain anatomical changes in Parkinson\u2019s disease.","volume":"33","author":"Lucas-Jimenez","year":"2016","journal-title":"Parkinsonism Relat. Disord."},{"key":"B32","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1136\/jnnp-2013-306237","article-title":"Resting-state fMRI study on drug-naive patients with Parkinson\u2019s disease and with depression.","volume":"85","author":"Luo","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B33","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/s004019900168","article-title":"Alpha-synuclein-immunoreactive cortical Lewy bodies are associated with cognitive impairment in Parkinson\u2019s disease.","volume":"100","author":"Mattila","year":"2000","journal-title":"Acta Neuropathol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.tins.2019.01.003","article-title":"Vitamin D in synaptic plasticity, cognitive function, and neuropsychiatric illness.","volume":"42","author":"Mayne","year":"2019","journal-title":"Trends Neurosci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1002\/mds.21317","article-title":"Vitamin D and Parkinson\u2019s disease - A hypothesis.","volume":"22","author":"Newmark","year":"2007","journal-title":"Mov. Disord."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1002\/mds.27115","article-title":"Past, present, and future of Parkinson\u2019s disease: a special essay on the 200th Anniversary of the Shaking Palsy.","volume":"32","author":"Obeso","year":"2017","journal-title":"Mov. Disord."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.936","article-title":"Serum vitamin D in patients with mild cognitive impairment and Alzheimer\u2019s disease.","volume":"8","author":"Ouma","year":"2018","journal-title":"Brain Behav."},{"key":"B38","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.jamda.2018.08.014","article-title":"Risk factors for vertebral, hip, and femoral fractures among patients with Parkinson\u2019s disease: a 5-year follow-up in Korea.","volume":"20","author":"Park","year":"2019","journal-title":"J. Am. Med. Directors Assoc."},{"key":"B39","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1096\/fj.201700713R","article-title":"Vitamin D regulation of GDNF\/Ret signaling in dopaminergic neurons.","volume":"32","author":"Pertile","year":"2018","journal-title":"FASEB J."},{"key":"B40","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.neulet.2013.12.053","article-title":"The role of vitamin D levels and vitamin D receptor polymorphism on Parkinson\u2019s disease in the Faroe Islands.","volume":"561","author":"Petersen","year":"2014","journal-title":"Neurosci. Lett."},{"key":"B41","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.maturitas.2014.02.012","article-title":"A review of vitamin D and Parkinson\u2019s disease.","volume":"78","author":"Peterson","year":"2014","journal-title":"Maturitas"},{"key":"B42","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.arr.2017.09.006","article-title":"Alpha-synuclein, epigenetics, mitochondria, metabolism, calcium traffic, & circadian dysfunction in Parkinson\u2019s disease. An integrated strategy for management.","volume":"40","author":"Phillipson","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"MDS clinical diagnostic criteria for Parkinson\u2019s disease.","volume":"30","author":"Postuma","year":"2015","journal-title":"Mov. Disord."},{"key":"B44","doi-asserted-by":"publisher","first-page":"4817","DOI":"10.3390\/nu7064817","article-title":"Associations between Vitamin D status, supplementation, outdoor work and risk of Parkinson\u2019s disease: a meta-analysis assessment.","volume":"7","author":"Shen","year":"2015","journal-title":"Nutrients"},{"key":"B45","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1002\/mds.26573","article-title":"Serum 25-hydroxyvitamin D concentrations in Mid-adulthood and Parkinson\u2019s disease risk.","volume":"31","author":"Shrestha","year":"2016","journal-title":"Mov. Disord."},{"key":"B46","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1007\/s11064-006-9048-4","article-title":"Calcitriol protection against dopamine loss induced by intracerebroventricular administration of 6-hydroxydopamine.","volume":"31","author":"Smith","year":"2006","journal-title":"Neurochem. Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1002\/mds.24016","article-title":"25-hydroxyvitamin D, vitamin D receptor gene polymorphisms, and severity of Parkinson\u2019s disease.","volume":"27","author":"Suzuki","year":"2012","journal-title":"Mov. Disord."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2226","DOI":"10.1212\/WNL.0b013e31827689d6","article-title":"Default-mode network connectivity in cognitively unimpaired patients with Parkinson disease.","volume":"79","author":"Tessitore","year":"2012","journal-title":"Neurology"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3390\/nu8030142","article-title":"Vitamin D and sunlight exposure in newly-diagnosed Parkinson\u2019s disease.","volume":"8","author":"Wang","year":"2016","journal-title":"Nutrients"},{"key":"B50","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1002\/mds.26117","article-title":"Vitamin D from different sources is inversely associated with Parkinson disease.","volume":"30","author":"Wang","year":"2015","journal-title":"Mov. Disord."},{"key":"B51","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/s12021-016-9299-4","article-title":"DPABI: data processing & analysis for (Resting-State) brain imaging.","volume":"14","author":"Yan","year":"2016","journal-title":"Neuroinformatics"},{"key":"B52","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1111\/cns.12838","article-title":"Abnormal resting-state functional connectivity in posterior cingulate cortex of Parkinson\u2019s disease with mild cognitive impairment and dementia.","volume":"24","author":"Zhan","year":"2018","journal-title":"CNS Neurosci. Ther."},{"key":"B53","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1631\/jzus.B1400005","article-title":"Inverse associations of outdoor activity and vitamin D intake with the risk of Parkinson\u2019s disease.","volume":"15","author":"Zhu","year":"2014","journal-title":"J. Zhejiang Univ. Sci. B"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2021.763947\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T08:08:35Z","timestamp":1639987715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2021.763947\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,20]]},"references-count":53,"alternative-id":["10.3389\/fnagi.2021.763947"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2021.763947","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,20]]},"article-number":"763947"}}