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However, non-invasive, in vivo neuroimaging studies investigating the underlying neural mechanisms of trigeminal system abnormalities in human migraine patients are limited.<\/jats:p>\n                  <jats:p>Here, we studied 60 patients with migraine (55 females, mean \u00b1 standard deviation age: 36.28 \u00b1 11.95 years) and 20 age- and sex-matched healthy controls (19 females, age: 35.45 \u00b1 13.30 years) using ultra-high field 7 T diffusion tensor imaging and functional MRI, in addition to PET with the translocator protein ligand 11C-PBR28. We evaluated MRI diffusivity measures and the PET signal at the trigeminal nerve root, in addition to the brainstem functional MRI response to innocuous ophthalmic trigeminal nerve territory stimulation.<\/jats:p>\n                  <jats:p>Patients with migraine demonstrated altered white matter microstructure at the trigeminal nerve root (n = 53), including reduced fractional anisotropy, in comparison to healthy controls (n = 18). Furthermore, in patients, lower fractional anisotropy was accompanied by higher neuroinflammation (i.e. elevated 11C-PBR28 PET signal) at the nerve root (n = 36) and by lower functional MRI activation in an ipsilateral pontine cluster consistent with the spinal trigeminal nucleus (n = 51). These findings were more robust on the right side, which was consistent with the observation that right headache-dominant patients demonstrated higher migraine severity in comparison to left headache-dominant patients in our cohort.<\/jats:p>\n                  <jats:p>Multimodal imaging of the integrated neural mechanisms that characterize migraine underscores the importance of trigeminal system remodelling as both a key aspect of the dynamics underlying migraine pathophysiology and a target for therapeutic interventions.<\/jats:p>","DOI":"10.1093\/brain\/awaf029","type":"journal-article","created":{"date-parts":[[2025,1,26]],"date-time":"2025-01-26T07:16:07Z","timestamp":1737875767000},"page":"2551-2562","source":"Crossref","is-referenced-by-count":17,"title":["Trigeminal nerve microstructure is linked with neuroinflammation and brainstem activity in migraine"],"prefix":"10.1093","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2439-3190","authenticated-orcid":false,"given":"Sarasa","family":"Tohyama","sequence":"first","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Datko","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Center for Mindfulness and Compassion, Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School , Cambridge, MA 02141 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Brusaferri","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Computer Science and Informatics, London South Bank University , London SE1 0AA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian D","family":"Kinder","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Center for Mindfulness and Compassion, Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School , Cambridge, MA 02141 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack H","family":"Schnieders","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie","family":"Hyman","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melaina D","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hope","family":"Housman","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vi","family":"Le","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kassandra","family":"Round","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Center for Mindfulness and Compassion, Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School , Cambridge, MA 02141 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Marin","sequence":"additional","affiliation":[{"name":"Center for Mindfulness and Compassion, Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School , Cambridge, MA 02141 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan R","family":"Heffernan","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald G","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02114 ,","place":["USA"]},{"name":"School of Medicine, Universidad de Santander , Bucaramanga 680006 ,","place":["Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy L","family":"Gollub","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce R","family":"Rosen","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouchine","family":"Hadjikhani","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsinlin T","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zev","family":"Schuman-Olivier","sequence":"additional","affiliation":[{"name":"Center for Mindfulness and Compassion, Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School , Cambridge, MA 02141 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-5265","authenticated-orcid":false,"given":"Marco L","family":"Loggia","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaly","family":"Napadow","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School , Boston, MA 02129 ,","place":["USA"]},{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"2025070715515764300_awaf029-B1","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/S0140-6736(17)32154-2","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990\u20132016: A systematic analysis for the global burden of disease study 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