Is There a Fibromyalgia “Brain Signature”?

Is There a Fibromyalgia “Brain Signature”?

—Researchers have discovered that fibromyalgia may be a systemic neurologic disorder that can be diagnosed using a functional MRI-based “brain signature.”

Fibromyalgia currently lacks a clear-cut, objective method to confirm its diagnosis, complicating clinicians’ jobs and frustrating patients. However, researchers may be getting much closer to identifying neurophysiological markers that are diagnostic of fibromyalgia.

Patients with fibromyalgia experience widespread pain, altered cognition, fatigue, and sleep dysfunction. On top of these burdensome symptoms, it often takes several years, several doctors, a few misdiagnoses, and numerous tests before a diagnosis of fibromyalgia is confirmed. What’s worse, these patients might have to fight an uphill battle to convince clinicians, family, friends, and coworkers that their condition is a “real” one.

Take Note

To provide an objective diagnostic marker for fibromyalgia, researchers recently used a multisensory approach to identify a brain signature that distinguishes individuals with fibromyalgia from individuals without it.


Of the 72 subjects who participated, all of whom were women, 37 had a confirmed diagnosis of fibromyalgia according to the 1990 American College of Rheumatology criteria.


The other 35 were healthy controls matched for age, education status, and handedness (all were right-handed).


Participants were exposed to visual and auditory stimulation and were asked to perform a finger opposition task.


A functional magnetic resonance imaging (fMRI) based neurologic pain signature (NPS) (previously validated to predict experimental pain and discriminate it from other unpleasant/arousing emotional experiences) was applied to the subjects during pain processing.


In addition, researchers discriminated patients with fibromyalgia from healthy controls using activation patterns during painful pressure (FM-pain) and during nonpainful multisensory stimulation.


Patients with fibromyalgia experienced greater NPS than healthy participants when exposed to the same painful stimuli. Furthermore, when pattern response values were combined for the NPS, FM pain, and multisensory patterns using logistic regression, this combined classifier was able to discriminate patients from healthy participants with 92% sensitivity (confidence interval [CI], 84% – 98%) and 94% specificity (CI, 87% – 100%).


Tor Wager, PhD, director of the cognitive and affective neuroscience laboratory and professor in the department of psychology and neuroscience and the Institute for Cognitive Science at the University of Colorado, Boulder, and author of the study, said, “Abnormal responses to multisensory events was the strongest individual predictor of whether a person had fibromyalgia. This suggests it is a systemic, rather than pain specific, neurological disorder.”

The identification of a fibromyalgia-specific brain signature has the potential to launch the medical community far ahead of the past notion that the condition was in patients’ heads. According to Daniel G. Arkfeld, MD, associate professor of clinical medicine at the Keck School of Medicine of the University of Southern California (USC), and director of rheumatological education at the Keck Hospital of USC, “It is an old idea that fibromyalgia is a made-up disorder and doesn’t exist. Results of studies such as this, as well as others that have shown high levels of substance P [a pain-promoting or algesic neurotransmitter] in the spinal fluid of patients within fibromyalgia,


show that there is a neuropathophysiologic basis for the unique syndrome of fibromyalgia.”The use of such a brain signature has implications beyond improving fibromyalgia diagnosis. “There is a need for objective measures in fibromyalgia. This research may help point toward appropriate targets for a more directed approach in treating fibromyalgia,” said Dr. Arkfeld. Dr. Wager concurred, “We need to diagnose patients and group them based on the underlying neuropathology. Then we have a better chance of finding the best treatments based on an individual’s biology.”

In other words, the use of fMRI technology to observe brain patterns in real time when patients with fibromyalgia are experiencing pain and multisensory stimulation may allow patients to be diagnosed using objective measures, and may also lead to advances in fibromyalgia treatment due to the enhanced understanding of the disorder it affords. There may come a time in the not-so-distant future when fibromyalgia enters its own era of targeted medicine, with therapies tailored to individual disease characteristics such as those included in the brain signature.


  • 1. López-Solà M, Woo CW, Pujol J, et al. Towards a neurophysiological signature for fibromyalgia. Pain. 2017;158:34-47.
  • 2. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990;33:160-172.
  • 3. Wager TD, Atlas LY, Lindquist MA, et al. An fMRI-based neurologic signature of physical pain. N Engl J Med. 2013;368:1388-1397.
  • 4. Liu Z, Welin M, Bragee B, et al. A high-recovery extraction procedure for quantitative analysis of substance P and opioid peptides in human cerebrospinal fluid. Peptides. 2000;21:853-860.
  • 5. Russell IJ, Orr MD, Littman B, et al. Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum. 1994;37:1593-1601.


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