{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:40:17Z","timestamp":1785458417212,"version":"3.56.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Although there have been many magnetic resonance spectroscopy (MRS) studies of migraine, few have focused on migraines during an attack. Here, we aimed to assess metabolite changes in the brain of patients with migraine, both during an attack and in the interictal phase.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Six patients (one man and five women, mean age: 39 \u00b1 10 years) with migraine without aura during the attack (MWoA-DA), 13 patients (three men and 10 women, mean age: 31 \u00b1 9 years) with migraine without aura during the interictal period (MWoA-DI), and 13 healthy controls (HC) (four men and nine women, mean age: 31 \u00b1 9 years) were studied. All subjects underwent an MRS examination focusing on the occipital lobe. Metabolite changes were investigated among three groups.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The MWoA-DA patients had lower glutathione\/total creatine ratio (GSH\/tCr) than the MWoA-DI patients and HC. Furthermore, MWoA-DI patients showed lower total choline\/total creatine ratio (tCho\/tCr) than those in the other two groups. The GSH\/tCr ratio was positively correlated with attack frequency in the MWoA-DI group. The tCho\/tCr ratio was positively correlated with attack frequency and Migraine Disability Assessment Scale (MIDAS) scores in the MWoA-DA group.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The present study suggests the existence of distinct pathophysiological states between the MWoA-DA and MWoA-DI groups. Neuronal dysfunction is a possible predisposing factor for migraine attack onset, along with oxidative stress and inflammation.<\/jats:p>","DOI":"10.3389\/fneur.2021.656349","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T05:21:10Z","timestamp":1621488070000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Altered Metabolites in the Occipital Lobe in Migraine Without Aura During the Attack and the Interictal Period"],"prefix":"10.3389","volume":"12","author":[{"given":"Luping","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengxiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1177\/0333102413485658","article-title":"The International Classification of Headache Disorders, 3rd edition (beta version)","volume":"33","year":"2013","journal-title":"Cephalalgia."},{"key":"B2","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/S0140-6736(15)60692-4","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990\u20132013: a systematic analysis for the Global Burden of Disease Study 2013","volume":"386","year":"2015","journal-title":"Lancet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/nrneurol.2013.192","article-title":"Cortical spreading depression and migraine","volume":"9","author":"Charles","year":"2013","journal-title":"Nat Rev Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/s41582-019-0216-y","article-title":"Does inflammation have a role in migraine?","volume":"15","author":"Edvinsson","year":"2019","journal-title":"Nat Rev Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1038\/nrn3057","article-title":"Diencephalic and brainstem mechanisms in migraine","volume":"12","author":"Akerman","year":"2011","journal-title":"Nat Rev Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/head.12725","article-title":"Migraine triggers and oxidative stress: a narrative review and synthesis","volume":"56","author":"Borkum","year":"2016","journal-title":"Headache."},{"key":"B7","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1177\/0333102412452048","article-title":"Magnetic resonance spectroscopy in migraine: what have we learned so far?","volume":"32","author":"Reyngoudt","year":"2012","journal-title":"Cephalalgia."},{"key":"B8","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s10194-018-0885-8","article-title":"Increased thalamic glutamate\/glutamine levels in migraineurs","volume":"19","author":"Bathel","year":"2018","journal-title":"J Headache Pain."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1093\/brain\/awx130","article-title":"Cortical glutamate in migraine","volume":"140","author":"Zielman","year":"2017","journal-title":"Brain."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2207","DOI":"10.1093\/cercor\/bhr248","article-title":"Abnormal changes of synaptic excitability in migraine with aura","volume":"22","author":"Siniatchkin","year":"2012","journal-title":"Cerebral Cortex."},{"key":"B11","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1212\/01.WNL.0000151855.98318.50","article-title":"1H-MRS alterations in the cerebellum of patients with familial hemiplegic migraine type 1","volume":"64","author":"Dichgans","year":"2005","journal-title":"Neurology."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1016\/j.jpain.2016.06.008","article-title":"The association between clinical characteristics of migraine and brain gaba levels: an exploratory study","volume":"17","author":"Aguila","year":"2016","journal-title":"J Pain."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1212\/01.wnl.0000313376.07248.28","article-title":"Occipital levels of GABA are related to severe headaches in migraine","volume":"70","author":"Bigal","year":"2008","journal-title":"Neurology."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1177\/0333102414566860","article-title":"Altered neurochemical coupling in the occipital cortex in migraine with visual aura","volume":"35","author":"Bridge","year":"2015","journal-title":"Cephalalgia."},{"key":"B15","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1177\/0333102414557048","article-title":"Increased myo-inositol level in dorsolateral prefrontal cortex in migraine patients with major depression","volume":"35","author":"Lirng","year":"2015","journal-title":"Cephalalgia."},{"key":"B16","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1179\/016164107X235473","article-title":"Metabolite concentration ratios in thalami of patients with migraine and trigeminal neuralgia measured with 1H-MRS","volume":"30","author":"Gu","year":"2008","journal-title":"Neurol Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1016\/j.mri.2003.08.021","article-title":"Cerebellar metabolite alterations detected in vivo by proton MR spectroscopy","volume":"21","author":"Macri","year":"2003","journal-title":"Magn Reson Imaging."},{"key":"B18","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1177\/0333102410392068","article-title":"Multimodal neuroimaging in a child with sporadic hemiplegic migraine: a contribution to understanding pathogenesis","volume":"31","author":"Toldo","year":"2011","journal-title":"Cephalalgia."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1111\/j.1468-2982.2006.01131.x","article-title":"Imaging abnormalities in sporadic hemiplegic migraine on conventional MRI, diffusion and perfusion MRI and MRS","volume":"26","author":"Jacob","year":"2006","journal-title":"Cephalalgia."},{"key":"B20","first-page":"749","article-title":"Evidence of vascular compromise over the visual cortex during migrainous headache: a case report with MRI study","volume":"93","author":"Chawalparit","year":"2010","journal-title":"J Med Assoc Thai."},{"key":"B21","doi-asserted-by":"publisher","first-page":"4687","DOI":"10.1073\/pnas.071582498","article-title":"Mechanisms of migraine aura revealed by functional MRI in human visual cortex","volume":"98","author":"Hadjikhani","year":"2001","journal-title":"Proc Natl Acad Sci USA."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1177\/0333102419840643","article-title":"Current understanding of cortical structure and function in migraine","volume":"39","author":"Tolner","year":"2019","journal-title":"Cephalalgia."},{"key":"B23","first-page":"S51","article-title":"Cortical spreading depression and central pain networks in trigeminal nuclei modulation: time for an integrated migraine pathogenesis perspective","volume-title":"Neurol Sci.","author":"De Simone","year":"2013"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1056\/NEJM199412223312505","article-title":"Brief report: bilateral spreading cerebral hypoperfusion during spontaneous migraine headache","volume":"331","author":"Woods","year":"1994","journal-title":"N Engl J Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1111\/head.12531","article-title":"Vision and migraine","volume":"55","author":"Vincent","year":"2015","journal-title":"Headache."},{"key":"B26","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/1129-2377-14-85","article-title":"Alterations in regional homogeneity assessed by fMRI in patients with migraine without aura stratified by disease duration","volume":"14","author":"Zhao","year":"2013","journal-title":"J Headache Pain."},{"key":"B27","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.crad.2016.03.004","article-title":"Amplitude of low-frequency fluctuation (ALFF) and fractional ALFF in migraine patients: a resting-state functional MRI study","volume":"71","author":"Wang","year":"2016","journal-title":"Clin Radiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1002\/jmri.26046","article-title":"Comparing the reproducibility of commonly used magnetic resonance spectroscopy techniques to quantify cerebral glutathione","volume":"49","author":"Wijtenburg","year":"2019","journal-title":"J Magn Reson Imaging."},{"key":"B29","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.mri.2019.03.020","article-title":"MEGA-PRESS and PRESS measure oxidation of glutathione in a phantom","volume":"60","author":"Brix","year":"2019","journal-title":"Magn Reson Imaging."},{"key":"B30","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.biopsych.2015.04.005","article-title":"Brain glutathione levels\u2013a novel biomarker for mild cognitive impairment and Alzheimer's disease","volume":"78","author":"Mandal","year":"2015","journal-title":"Biol Psychiatry."},{"key":"B31","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1038\/s41380-018-0104-7","article-title":"Glutathione and glutamate in schizophrenia: a 7T MRS study","volume":"25","author":"Kumar","year":"2020","journal-title":"Mol Psychiatry."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1111\/epi.16731","article-title":"Seven-tesla quantitative magnetic resonance spectroscopy of glutamate, gamma-aminobutyric acid, and glutathione in the posterior cingulate cortex\/precuneus in patients with epilepsy","volume":"61","author":"Gonen","year":"2020","journal-title":"Epilepsia."},{"key":"B33","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.ab.2016.12.022","article-title":"Glutathione in the human brain: Review of its roles and measurement by magnetic resonance spectroscopy","volume":"529","author":"Rae","year":"2017","journal-title":"Anal Biochem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1007\/s11064-020-03030-1","article-title":"Glutathione in brain: overview of its conformations, functions, biochemical characteristics, quantitation and potential therapeutic role in brain disorders","volume":"45","author":"Dwivedi","year":"2020","journal-title":"Neurochem Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1620\/tjem.211.23","article-title":"Increased nitrosative and oxidative stress in platelets of migraine patients","volume":"211","author":"Yilmaz","year":"2007","journal-title":"Tohoku J Exp Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1111\/papr.12902","article-title":"Reduction in migraine and headache frequency and intensity with combined antioxidant prophylaxis (N-acetylcysteine, Vitamin E, and Vitamin C): a randomized sham-controlled pilot study","volume":"20","author":"Visser","year":"2020","journal-title":"Pain Pract."},{"key":"B37","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/s41582-019-0255-4","article-title":"The metabolic face of migraine\u2014from pathophysiology to treatment","volume":"15","author":"Gross","year":"2019","journal-title":"Nat Rev Neurol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"464","DOI":"10.3390\/antiox9060494","article-title":"Retinal nerve fiber layer thickness and oxidative stress parameters in migraine patients without aura: a pilot study","volume":"9","author":"Bulboaca","year":"2020","journal-title":"Antioxidants."},{"key":"B39","doi-asserted-by":"publisher","first-page":"367","DOI":"10.2147\/NDT.S156710","article-title":"Oxidative\/antioxidative status, lymphocyte DNA damage, and urotensin-2 receptor level in patients with migraine attacks","volume":"14","author":"Yigit","year":"2018","journal-title":"Neuropsychiatr Dis Treat."},{"key":"B40","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s10194-016-0606-0","article-title":"Oxidative stress and DNA damage in patients with migraine","volume":"17","author":"Geyik","year":"2016","journal-title":"J Headache Pain."},{"key":"B41","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/s12883-019-1555-4","article-title":"An investigation of oxidant\/antioxidant balance in patients with migraine: a case-control study","volume":"19","author":"Togha","year":"2019","journal-title":"BMC Neurol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1007\/s10072-020-04626-9","article-title":"Frontal lobe metabolic alterations characterizing Parkinson's disease cognitive impairment","volume":"42","author":"Chaudhary","year":"2020","journal-title":"Neurol Sci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"234","DOI":"10.3390\/brainsci11020234","article-title":"Pain-related brain connectivity changes in migraine: a narrative review and proof of concept about possible novel treatments interference","volume":"11","author":"de Tommaso","year":"2021"},{"key":"B44","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1111\/j.1468-2982.2005.01059.x","article-title":"Mitochondrial dysfunction and migraine: evidence and hypotheses","volume":"26","author":"Sparaco","year":"2006","journal-title":"Cephalalgia."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1097\/j.pain.0000000000001815","article-title":"Magnetic resonance imaging of neuroinflammation in chronic pain: a role for astrogliosis?","volume":"161","author":"Jung","year":"2020","journal-title":"Pain."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e805","DOI":"10.1212\/WNL.0000000000010003","article-title":"Metabolites of neuroinflammation relate to neuropathic pain after spinal cord injury","volume":"95","author":"Pfyffer","year":"2020","journal-title":"Neurology."},{"key":"B47","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1007\/s11481-013-9460-x","article-title":"Magnetic resonance spectroscopy to assess neuroinflammation and neuropathic pain","volume":"8","author":"Chang","year":"2013","journal-title":"J Neuroimmune Pharmacol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"7359235","DOI":"10.1155\/2019\/7359235","article-title":"Effects of DCM leaf extract of gnidia glauca (fresen) on locomotor activity, anxiety, and exploration-like behaviors in high-fat diet-induced obese rats","volume":"2019","author":"Arika","year":"2019","journal-title":"Behav Neurol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1177\/0333102417702132","article-title":"Astrocyte-mediated inflammation in cortical spreading depression","volume":"38","author":"Ghaemi","year":"2018","journal-title":"Cephalalgia."},{"key":"B50","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1002\/ana.20778","article-title":"Suppression of cortical spreading depression in migraine prophylaxis","volume":"59","author":"Ayata","year":"2006","journal-title":"Ann Neurol."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.656349\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T05:21:14Z","timestamp":1621488074000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.656349\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,20]]},"references-count":50,"alternative-id":["10.3389\/fneur.2021.656349"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.656349","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,20]]},"article-number":"656349"}}