{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:27:13Z","timestamp":1789176433588,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T00:00:00Z","timestamp":1592784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To understand the changes in functional connectivity between brain areas of potential importance in migraine during different phases of the attack.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Migraine is a symptomatically heterogeneous disorder. Understanding the possible changes in brain function and, therefore, neurobiology during different phases of the migraine attack is important in developing disease biomarkers and advancing therapeutics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Randomized, double\u2010blind, placebo\u2010controlled, multi\u2010visit experimental study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Subjects aged 18\u201050\u00a0years with migraine with and without aura (\u226422 headache days per month) were recruited from across the UK using advertising, from both population and hospital clinic samples (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a053). Consented subjects were randomized to a 0.5\u00a0\u00b5g\/kg\/min nitroglycerin infusion or to placebo over 20\u00a0minutes across different study visits, during the period February 2015\u2010July 2017.* All subjects were exposed to a nitroglycerin infusion at least on 1 occasion at screening.** For those subjects who consented to participate in imaging visits (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a025), structural T1, T2 and FLAIR sequences and resting state blood oxygen level dependant contrast (rsBOLD) time series, using a multiecho EPI sequence, were conducted over 30\u201040\u00a0minutes at baseline and rsBOLD during premonitory symptoms and migraine headache on a 3T General Electric MR750 MRI scanner. For the placebo visit, the imaging was conducted at the same times following infusion in the absence of symptoms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Montreal Neurological Institute (MNI) coordinates were used to characterize identified brain areas of connectivity change. Using repeated measures ANOVA models with time (visit number) and trigger substance (nitroglycerin\/placebo) as factors, significant positive functional coupling was found between the thalami bilaterally and the right precuneus and cuneus regions during the nitroglycerin\u2010triggered premonitory phase (\n                      <jats:italic>T<\/jats:italic>\n                      \u00a0=\u00a03.23, peak connectivity change at [\u22126, \u221268, 40] for left thalamus,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.012 and [\u22124, \u221268, 40] for right thalamus,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.019). The nitroglycerin\u2010triggered premonitory phase was associated with a change in the direction of connectivity from positive to negative between the pons and the limbic lobe (\n                      <jats:italic>T<\/jats:italic>\n                      \u00a0=\u00a03.47, peak connectivity change at [2, 8, 50],\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). The headache phase of the nitroglycerin\u2010triggered migraine attack was associated with ongoing negative functional coupling between the pons and the cingulate and frontal cortices, and positive functional coupling between the pons and the cerebellar tonsils and medulla (\n                      <jats:italic>T<\/jats:italic>\n                      \u00a0=\u00a03.47, peak connectivity change at [\u22128, \u221252, \u221258],\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.007).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Understanding the functional reorganization between subcortical and cortical brain areas in different phases of the migraine attack provides novel insights into the abnormal sensory processing and integration during migraine, as well as functional correlation with clinical symptoms displayed during each phase.<\/jats:p>\n                    <jats:p>[*Correction added on July 22, 2020 after first online publication: This sentence was revised from, \u201cConsented subjects had a 0.5 \u03bcg\/kg\/min nitroglycerin infusion\u2026\u201d.]<\/jats:p>\n                    <jats:p>[**Correction added on July 22, 2020 after first online publication: This sentence was revised from, \u201c\u2026 at least on 1 occasion at screening.\u201d]<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.13865","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T11:58:43Z","timestamp":1592827123000},"page":"1244-1258","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Alterations in Functional Connectivity During Different Phases of the Triggered Migraine 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen","family":"O\u2019Daly","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Centre for Neuroimaging Sciences Institute of Psychiatry, Psychology and Neuroscience King\u2019s College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando O.","family":"Zelaya","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging Centre for Neuroimaging Sciences Institute of Psychiatry, Psychology and Neuroscience King\u2019s College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Goadsby","sequence":"additional","affiliation":[{"name":"Headache Group Department of Basic and Clinical Neuroscience Institute of Psychiatry, Psychology and Neuroscience King\u2019s College London London UK"},{"name":"NIHR\u2010Wellcome Trust King\u2019s Clinical Research Facility SLaM Biomedical Research Centre King\u2019s 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