Structural and Functional Neuroimaging Findings in Fibromyalgia: A Systematic Review.

Overview

1. Pain Center, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil
2. Graduate Program in Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil
3. Emotion Neurophysiology Laboratory, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil
4. Programa de Pós‐Graduação Em Neurociências Translacional (PGNET), Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
5. Department of Radiology, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil
6. Discipline of Neurosurgery, Faculty of Medical Sciences, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil

Abstract

Background and Objective: Fibromyalgia (FM) is a nociplastic chronic pain syndrome in which neuroimaging indicates central nervous system involvement, yet findings remain inconsistent across methods. We systematically reviewed structural and functional neuroimaging studies in adults with FM to identify the most reproducible cross‐modal alterations.

Databases and Data Treatment: Following a PROSPERO‐registered protocol (CRD420251234980) and PRISMA 2020, we searched PubMed, EMBASE, Web of Science and VHL/BVS for English‐language studies published between 1 January 2010 and 16 October 2025. Eligible studies compared FM (any American College of Rheumatology criteria) with healthy controls and reported quantitative structural MRI, diffusion/structural connectivity or resting‐state/task‐based fMRI.

Results: Ninety‐one studies were included (24 morphometry, 8 diffusion/structural connectivity, 32 resting‐state fMRI, 40 task‐based fMRI). Morphometry most consistently showed reduced grey matter volume or cortical thickness in anterior cingulate, insular and prefrontal/orbitofrontal cortices, with recurrent reductions in temporal cortex, posterior cingulate, amygdala and hippocampus; thalamic increases were less frequent. Diffusion findings were sparse and bidirectional, yielding no stable white‐matter alterations. Resting‐state fMRI was highly heterogeneous, with contradictory default‐mode, salience/insula and periaqueductal grey (PAG)‐related connectivity changes. Task‐based fMRI provided the clearest support for central sensitization, showing hyper‐responsivity of nociceptive networks with dysregulated prefrontal engagement and weakened rostral anterior cingulate cortex (rACC)–PAG/brainstem descending modulation.

Conclusions: FM shows distributed brain alterations, with the most robust signals reflecting nociceptive amplification and impaired top‐down control. Harmonized longitudinal multimodal studies are needed to establish reliable biomarkers.

Significance Statement: This systematic review shows that fibromyalgia neuroimaging findings are not best explained by a single biomarker, but by distributed alterations across pain‐processing, modulatory and affective‐cognitive systems. By comparing structural MRI, diffusion imaging, resting‐state fMRI and task‐based fMRI, the review identifies task‐evoked nociceptive amplification and impaired descending modulation as the most coherent cross‐study signal, while clarifying why resting‐state and diffusion findings remain difficult to translate clinically.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• zenodo:20692808 — at Zenodo; found in “Data Availability Statement”

Data Availability Statement

The datasets and Supporting Information generated and analysed during the current study are publicly available in the Zenodo repository at https://doi.org/10.5281/zenodo.20692808.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 2, 28 September 2026

• Publisher: — → Wiley

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 7 MeSH terms, 136 references.

Cite

This paper

Flutt, F. A. D., de Melo Cortez, J. P., Ramos, L. R., Furlanetto, R. P. P., Corrêa, D. G., & Villela, N. R. (2026). Structural and Functional Neuroimaging Findings in Fibromyalgia: A Systematic Review. European journal of pain (London, England), 30(6), e70331. https://doi.org/10.1002/ejp.70331

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