Resting state electrical brain activity and connectivity in fibromyalgia
June
Resting state electrical brain activity and connectivity in fibromyalgia
Sven Vanneste 1 2
Jan Ost 0 2
Tony Van Havenbergh 0 2
Dirk De Ridder 2
0 N, Sint Augustinus Hospital Antwerp, Antwerp, Belgium, 3 Department of Surgical Sciences, Section of Neurosurgery, Dunedin School of Medicine, University of Otago , Dunedin , New Zealand
1 School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, United States of America , 2 BRAI , USA
2 Editor: Kewei Chen, Banner Alzheimer's Institute , UNITED STATES
The exact mechanism underlying fibromyalgia is unknown, but increased facilitatory modulation and/or dysfunctional descending inhibitory pathway activity are posited as possible mechanisms contributing to sensitization of the central nervous system. The primary goal of this study is to identify a fibromyalgia neural circuit that can account for these abnormalities in central pain. The second goal is to gain a better understanding of the functional connectivity between the default and the executive attention network (salience network plus dorsal lateral prefrontal cortex) in fibromyalgia. We examine neural activity associated with fibromyalgia (N = 44) and compare these with healthy controls (N = 44) using resting state source localized EEG. Our data support an important role of the pregenual anterior cingulate cortex but also suggest that the degree of activation and the degree of integration between different brain areas is important. The inhibition of the connectivity between the dorsal lateral prefrontal cortex and the posterior cingulate cortex on the pain inhibitory pathway seems to be limited by decreased functional connectivity with the pregenual anterior cingulate cortex. Our data highlight the functional dynamics of brain regions integrated in brain networks in fibromyalgia patients.
Introduction
Physiological pain typically originates from noxious stimuli that are able to trigger a neural
response in pain-dedicated systems. In individuals with fibromyalgia, pain is experienced with
noxious stimulation, but linked to abnormalities in central pain processing. Fibromyalgia is a
disorder characterized by chronic (>3 months) complaints of spontaneous widespread pain in
in all 4 quadrants of the body associated with fatigue not relieved by rest, poor sleep, distress,
depression, or cognitive dysfunction [1].
The exact mechanism underlying this pain syndrome is not known, but increased
facilitatory modulation and/or dysfunctional descending inhibitory pathway activity are possible
mechanisms contributing to sensitization of the central nervous system [2]. Central
sensitization is defined as an increased responsiveness of the central nervous system to a variety of
stimuli such as pressure and temperature. This causes hyperalgesia, allodynia, and referred
pain across multiple spinal segments, leading to chronic widespread pain [3]. Functional
and structural neuroimaging studies have provided evidence for this hypothesis,
demonstrating both structural and functional activity and connectivity changes resulting in
enhanced pain facilitation in combination with defective inhibition of nociceptive signals,
which augment pain perception [4, 5]. Activity changes have been identified in the insula,
the anterior cingulate cortex, and the prefrontal cortex [6]. These areas are part of what
used to be called the pain matrix, but has recently been shown to be non-specific for pain, as
these areas are also activated by non-painful stimuli, auditory stimuli, and visual stimuli [7].
Based on previous studies looking into salience processing [8], it has been suggested that the
pain matrix is actually a network involved in multimodal salience processing [
9, 10
]. Brain
resting state functional connectivity changes were identified in the self-referential default
mode network and the executive control network in fibromyalgia patients [6, 11±15].
These network changes in fibromyalgia are similar to what was found in chronic back pain
patients, which was interpreted as a lasting effect of pain on brain function [
16, 17
]. A
deficiency of the pain inhibitory pathways, which critically involve the pregenual anterior
cingulate cortex (pgACC) has been found in fibromyalgia patients as well [
4, 18
]. In summary,
functional imaging data suggest fibromyalgia is a clinical syndrome associated with a brain
dysfunction related to an increase in salience attached to pain and a deficiency in pain
inhibitory mechanisms.
In the current study, we examined neural activity associated with fibromyalgia using resting
state source localized EEG. The primary goal of this study was to identify a
fibromyalgiarelated neural circuit that could account for these abnormalities in central pain. The second
goal was to gain a better understanding of the functional connectivity between default and the
executive attention network in fibromyalgia. In addition, we were able to explore potential
abnormalities in different (...truncated)