Targeted limbic self-neuromodulation for alleviating central sensitization symptoms in fibromyalgia

Abstract Background Fibromyalgia (FM), involving somatic, cognitive, and affective domains is often regarded as a hallmark central sensitization syndrome. Despite limited current therapeutic options, emerging understanding of its neural underpinnings offers the potential of applying novel neuromodul...

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Main Authors: Ayelet Or-Borichev, Yulia Lerner, Yael Hamrani, Guy Gurevitch, Netali Mor, Maayan Doron, Noam Sarna, Jacob N. Ablin, Talma Hendler, Haggai Sharon
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Medicine
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Online Access:https://doi.org/10.1186/s12916-025-04138-3
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author Ayelet Or-Borichev
Yulia Lerner
Yael Hamrani
Guy Gurevitch
Netali Mor
Maayan Doron
Noam Sarna
Jacob N. Ablin
Talma Hendler
Haggai Sharon
author_facet Ayelet Or-Borichev
Yulia Lerner
Yael Hamrani
Guy Gurevitch
Netali Mor
Maayan Doron
Noam Sarna
Jacob N. Ablin
Talma Hendler
Haggai Sharon
author_sort Ayelet Or-Borichev
collection DOAJ
description Abstract Background Fibromyalgia (FM), involving somatic, cognitive, and affective domains is often regarded as a hallmark central sensitization syndrome. Despite limited current therapeutic options, emerging understanding of its neural underpinnings offers the potential of applying novel neuromodulation strategies. Specifically, limbic dysregulation underlying abnormalities in pain modulation and somatic-affective processing, has been shown to play a key role in FM. Here, we assessed the long-term efficacy of targeted limbic self-neuromodulation for improving clinical disease burden in FM. Methods Forty-seven patients with FM participated in a double-blind, randomized, dual-control study employing a novel specialized neurofeedback probe representing amygdala activity. Patients underwent 10 sessions of either genuine neurofeedback training (NFT = 21), or sham neurofeedback training (NFS = 13), or treatment as usual (TAU = 13). Disease severity and symptom burden were assessed using the Symptom Severity Score (SSS), along with other questionnaires administered before and after treatment. A clinical follow-up was performed 10–12 months post-intervention. Results NFT led to a significant immediate and long-term reduction in the SSS (F(2,40) = 7.32, p = 0.00, ηp2 = 0.27) and the Fibromyalgia Impact Questionnaire (FIQ) (F(2,40) = 9.85, p = 0.00, ηp2 = 0.33), alongside multidomain short- and long-term clinical benefits. NFS resulted in a long-term reduction in pain but did not affect other disease measures or overall disease burden. The TAU group showed no clinical improvements. Conclusions Our findings support the intimate involvement of limbic brain areas in the pathophysiology of FM and suggest that targeted neuromodulation offers a novel, mechanism-based approach for managing multidomain symptoms in FM. Trial registration This study was preregistered with the National Institutes of Health (NIH). Registration number: NCT02146495. Name of trial registry: Targeted Limbic Self-modulation as a Potential Treatment for Patients Suffering From Fibromyalgia  https://clinicaltrials.gov/study/NCT02146495 .
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spelling doaj-art-20e3fea7f3824b1dade59cea6f5743d32025-08-20T03:16:34ZengBMCBMC Medicine1741-70152025-05-0123111610.1186/s12916-025-04138-3Targeted limbic self-neuromodulation for alleviating central sensitization symptoms in fibromyalgiaAyelet Or-Borichev0Yulia Lerner1Yael Hamrani2Guy Gurevitch3Netali Mor4Maayan Doron5Noam Sarna6Jacob N. Ablin7Talma Hendler8Haggai Sharon9Sagol Brain Institute, Tel-Aviv Sourasky Medical CenterSagol Brain Institute, Tel-Aviv Sourasky Medical CenterSagol Brain Institute, Tel-Aviv Sourasky Medical CenterSagol Brain Institute, Tel-Aviv Sourasky Medical CenterSagol Brain Institute, Tel-Aviv Sourasky Medical CenterSagol Brain Institute, Tel-Aviv Sourasky Medical CenterGershon H. Gordon Faculty of Social Sciences, School of Psychological Sciences, Tel-Aviv UniversityFaculty of Medical and Health Sciences, Tel-Aviv UniversitySagol Brain Institute, Tel-Aviv Sourasky Medical CenterSagol Brain Institute, Tel-Aviv Sourasky Medical CenterAbstract Background Fibromyalgia (FM), involving somatic, cognitive, and affective domains is often regarded as a hallmark central sensitization syndrome. Despite limited current therapeutic options, emerging understanding of its neural underpinnings offers the potential of applying novel neuromodulation strategies. Specifically, limbic dysregulation underlying abnormalities in pain modulation and somatic-affective processing, has been shown to play a key role in FM. Here, we assessed the long-term efficacy of targeted limbic self-neuromodulation for improving clinical disease burden in FM. Methods Forty-seven patients with FM participated in a double-blind, randomized, dual-control study employing a novel specialized neurofeedback probe representing amygdala activity. Patients underwent 10 sessions of either genuine neurofeedback training (NFT = 21), or sham neurofeedback training (NFS = 13), or treatment as usual (TAU = 13). Disease severity and symptom burden were assessed using the Symptom Severity Score (SSS), along with other questionnaires administered before and after treatment. A clinical follow-up was performed 10–12 months post-intervention. Results NFT led to a significant immediate and long-term reduction in the SSS (F(2,40) = 7.32, p = 0.00, ηp2 = 0.27) and the Fibromyalgia Impact Questionnaire (FIQ) (F(2,40) = 9.85, p = 0.00, ηp2 = 0.33), alongside multidomain short- and long-term clinical benefits. NFS resulted in a long-term reduction in pain but did not affect other disease measures or overall disease burden. The TAU group showed no clinical improvements. Conclusions Our findings support the intimate involvement of limbic brain areas in the pathophysiology of FM and suggest that targeted neuromodulation offers a novel, mechanism-based approach for managing multidomain symptoms in FM. Trial registration This study was preregistered with the National Institutes of Health (NIH). Registration number: NCT02146495. Name of trial registry: Targeted Limbic Self-modulation as a Potential Treatment for Patients Suffering From Fibromyalgia  https://clinicaltrials.gov/study/NCT02146495 .https://doi.org/10.1186/s12916-025-04138-3Brain-based therapyFMRI-informed EEG modelNon-invasive interventionChronic pain reliefFibromyalgia management
spellingShingle Ayelet Or-Borichev
Yulia Lerner
Yael Hamrani
Guy Gurevitch
Netali Mor
Maayan Doron
Noam Sarna
Jacob N. Ablin
Talma Hendler
Haggai Sharon
Targeted limbic self-neuromodulation for alleviating central sensitization symptoms in fibromyalgia
BMC Medicine
Brain-based therapy
FMRI-informed EEG model
Non-invasive intervention
Chronic pain relief
Fibromyalgia management
title Targeted limbic self-neuromodulation for alleviating central sensitization symptoms in fibromyalgia
title_full Targeted limbic self-neuromodulation for alleviating central sensitization symptoms in fibromyalgia
title_fullStr Targeted limbic self-neuromodulation for alleviating central sensitization symptoms in fibromyalgia
title_full_unstemmed Targeted limbic self-neuromodulation for alleviating central sensitization symptoms in fibromyalgia
title_short Targeted limbic self-neuromodulation for alleviating central sensitization symptoms in fibromyalgia
title_sort targeted limbic self neuromodulation for alleviating central sensitization symptoms in fibromyalgia
topic Brain-based therapy
FMRI-informed EEG model
Non-invasive intervention
Chronic pain relief
Fibromyalgia management
url https://doi.org/10.1186/s12916-025-04138-3
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