Evidence map›Paper›PMID 41652332›Full record

ArticleThe journal of headache and pain2026

Multimodal MRI of episodic cluster headache reveals frontal cortical alterations and network-level connectivity changes.

Francesca Caramia, Antonio Di Renzo, Irene Giardina, Davide Chiffi, Giada Giuliani, Gabriele Sebastianelli, Francesco Casillo, Chiara Abagnale, Francesca Conti, Francesca Lafavia and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The journal of headache and pain, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Francesca Caramia *Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy. francesca.caramia@uniroma1.it.
Antonio Di Renzo *Diagnostic Department - Neuroradiology - Hospital S. Maria, Terni, Italy. antoniomp777@hotmail.it.
Irene Giardina *Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
Davide ChiffiDepartment of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
Giada GiulianiDepartment of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
Gabriele SebastianelliDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Latina, Italy.
Francesco CasilloDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Latina, Italy.
Chiara AbagnaleDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Latina, Italy.
Francesca ContiDepartment of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
Francesca LafaviaNeuroradiology Unit, Policlinico Umberto I, Rome, Italy.
Marco FiorelliDepartment of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
Mao-Mei SongLaboratory for Brain Science and Neuropsychiatric Diseases, Department of Neurology, Headache Center, Shanxi Provincial, The First Hospital of Shanxi Medical University, Shanxi Medical University, Shanxi, China.
Marta AltieriDepartment of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
Gianluca CoppolaDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Latina, Italy. gianluca.coppola@uniroma1.it.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCluster headache (CH) is a primary headache disorder characterized by circadian rhythmicity and autonomic symptoms. While the posterior hypothalamus has been historically implicated, converging evidence now supports a distributed, network-level dysfunction involving cortical and subcortical regions. This study aimed to: (1) assess whole-brain cortical thickness alterations in episodic CH (eCH) during the bout period, (2) examine their associations with clinical burden, and (3) investigate resting-state functional connectivity patterns of cortical regions showing structural alterations.

methodsWe investigated whole-brain cortical thickness and subcortical volumes in 26 patients with episodic CH scanned during the bout period but outside of attacks and 20 matched healthy controls (HC) using surface-based morphometry (FreeSurfer). Associations between cortical thickness and clinical variables (attack frequency, duration, disease history, and pain intensity) were assessed using general linear models corrected for multiple comparisons. Resting-state functional connectivity (FC) was further analyzed using seed-to-voxel correlations in the CONN toolbox, with seeds placed in cortical regions showing significant thinning.

resultsCompared with HC, eCH patients showed cortical thinning in the right inferior frontal gyrus (pars triangularis, BA45) and left superior frontal gyrus (BA9/10) (p < 0.05, Bonferroni correction). No significant subcortical volumetric differences were observed. Cortical thickness showed significant positive associations with clinical burden in associative parietal and occipital regions (p < 0.01, Bonferroni correction). Seed-based FC analyses revealed decreased coupling between the left superior frontal gyrus and right supramarginal cortex, but increased connectivity with the left precentral gyrus. Conversely, the right inferior frontal gyrus showed widespread hyperconnectivity with bilateral insulae, supramarginal, and sensorimotor cortices, and decreased connectivity with the right superior frontal region.

conclusionsThese findings identify coexisting structural and functional alterations within frontal cortices and their distributed targets, suggesting a differential reorganization of frontal attentional and sensorimotor networks in eCH. The pattern of fronto-parietal disconnection and fronto-insular hyperconnectivity extends the network model of cluster headache beyond the well-established hypothalamic–thalamic dysregulation. Together, these results strengthen the concept of cluster headache as a network-level disorder involving both executive and sensorimotor control systems.

Indexed as

Cluster HeadacheFrontal LobeNerve NetAdultFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedMultimodal ImagingNeural PathwaysCluster headacheCONN toolboxCortical thicknessFunctional connectivityInferior frontal gyrusPain networksSuperior frontal gyrusSurface-based morphometry

Identifiers

PMID41652332
PMCPMC12973639

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.