Attempt to replicate voxel-based morphometry analysis in fibromyalgia: Detection of below threshold differences framed by contributions of variable clinical presentation to low reproducibility

Abstract

Background: Fibromyalgia is a prevalent chronic pain condition characterized by widespread pain and sensory hypersensitivity. While much remains unknown about the neurobiological underpinnings of fibromyalgia, central nervous system alterations appear to be heavily implicated in its pathophysiology. Previous research examining brain structural abnormalities associated with fibromyalgia has yielded inconsistent findings. Thus, we followed previous methods to examine brain gray matter differences in fibromyalgia. We hypothesized that, relative to healthy controls, participants with fibromyalgia would exhibit lower gray matter volume in regions consistently implicated in fibromyalgia: the anterior cingulate cortex and medial prefrontal cortex. Methods: This study used magnetic resonance imaging to evaluate regional and whole brain differences in gray matter among females with and without fibromyalgia. Group differences were analyzed with two-sample t-tests, controlling for total intracranial volume. Results: No significant differences in regional or whole brain gray matter volumes were detected between fibromyalgia and healthy controls. Conclusions: Results add to an existing body of disparate findings regarding brain gray matter volume differences in fibromyalgia, and suggest structural differences previously detected in fibromyalgia should be examined for reproducibility. Absent significant differences may also suggest that functional, but not structural, brain adaptations are primarily associated with fibromyalgia.

A systematic review and meta-analysis of voxel-based morphometric studies of fibromyalgia

“…The search strategy resulted in 1,324 articles, and 12 articles were included in this meta-analysis ( Figure 1 ) (Kuchinad et al, 2007 ; Schmidt-Wilcke et al, 2007 ; Hsu et al, 2009 ; Wood et al, 2009 ; Ceko et al, 2013 ; Fallon et al, 2013 ; Diaz-Piedra et al, 2016 ; Pomares et al, 2017 ; Sundermann et al, 2019 ; Boehme et al, 2020 ; Müller et al, 2021 ; Baker et al, 2022 ). One study included two subgroups of fibromyalgia and did separate comparison analyses, so the study was considered separately into two studies for the meta-analysis (Ceko et al, 2013 ).…”

“…As a result, the number of studies in meta-analysis was elevated to 13. Among these studies, 9 studies reported gray matter decrease or increase or both in FM patients (Kuchinad et al, 2007 ; Schmidt-Wilcke et al, 2007 ; Wood et al, 2009 ; Ceko et al, 2013 ; Fallon et al, 2013 ; Diaz-Piedra et al, 2016 ; Pomares et al, 2017 ; Boehme et al, 2020 ), while 4 studies reported no abnormalities between FM patients and HS (Hsu et al, 2009 ; Sundermann et al, 2019 ; Müller et al, 2021 ; Baker et al, 2022 ). A total of 561 subjects were considered in this study, including 289 FM patients (mean age: 47.36 years) and 272 HS (mean age: 47.34 years).…”

“…The included articles in present study used several pain-related scales that couldn't be converted amongst one another, so the results of meta-regression analysis might not be robust. Besides, only 5 of 13 researches reported the medication used in the FM patients (Ceko et al, 2013 ; Diaz-Piedra et al, 2016 ; Boehme et al, 2020 ; Müller et al, 2021 ; Baker et al, 2022 ) and fewer researches reported the emotion state of FM patients, so we can't perform meta-regression analysis to observe the effect of medication taken and emotion state on gray matter changes of FM patients. Furthermore, it is evident that the prevalence of FM in females is obviously higher than that in males (Jones et al, 2015 ).…”