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Record W4406911589 · doi:10.1093/brain/awaf029

Trigeminal nerve microstructure is linked with neuroinflammation and brainstem activity in migraine

2025· article· en· W4406911589 on OpenAlexfundno aff
Sarasa Tohyama, Michael Datko, Ludovica Brusaferri, Lillian Kinder, Jack H. Schnieders, Mackenzie Hyman, Alison M. Goldstein, M. Gilbert, Hope Housman, Vi Donna Le, Kassandra Round, Megan Heffernan, Ronald G. García, Randy L. Gollub, Robert R. Edwards, Bruce R. Rosen, Nouchine Hadjikhani, Hsinlin T. Cheng, Zev Schuman‐Olivier, Marco L. Loggia, Vitaly Napadow

Bibliographic record

VenueBrain · 2025
Typearticle
Languageen
FieldMedicine
TopicMigraine and Headache Studies
Canadian institutionsnot available
FundersNational Center for Complementary and Integrative HealthNational Institute of Arthritis and Musculoskeletal and Skin DiseasesKorea Institute of Oriental MedicineNational Institute of Mental HealthNational Institutes of HealthCanadian Institutes of Health Research
KeywordsMigraineFractional anisotropyMedicineTrigeminal nerveBrainstemChronic MigraineSpinal trigeminal nucleusDiffusion MRINeuroscienceAnesthesiaMagnetic resonance imagingNociceptionInternal medicinePsychologyRadiologyReceptor

Abstract

fetched live from OpenAlex

Although the pathophysiology of migraine involves a complex ensemble of peripheral and CNS changes that remain incompletely understood, the activation and sensitization of the trigeminovascular system are believed to play a major role. However, non-invasive, in vivo neuroimaging studies investigating the underlying neural mechanisms of trigeminal system abnormalities in human migraine patients are limited. Here, we studied 60 patients with migraine (55 females, mean ± standard deviation age: 36.28 ± 11.95 years) and 20 age- and sex-matched healthy controls (19 females, age: 35.45 ± 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. 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. 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.674
Threshold uncertainty score0.460

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.272
Teacher spread0.263 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations14
Published2025
Admission routes1
Has abstractyes

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