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

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.