Fibromyalgia is associated with decreased connectivity between pain- and sensorimotor brain areas

Abstract

Fibromyalgia (FM) is a syndrome characterized by chronic pain without known peripheral causes. Previously, we have reported dysfunctional pain inhibitory mechanisms for FM patients during pain administration. In this study we employed a seed correlation analysis, independent component analysis (ICA), and an analysis of fractional amplitude of low frequency fluctuations (fALFF) to study differences between a cohort of female FM patients and an age- and sex-matched healthy control group during a resting-state condition. FM patients showed decreased connectivity between thalamus and premotor areas, between the right insula and primary sensorimotor areas, and between supramarginal and prefrontal areas. Individual sensitivity to painful pressure was associated with increased connectivity between pain-related regions (e.g., insula and thalamus) and midline regions of the default mode network (including posterior cingulate cortex and medial prefrontal cortex) among patients and controls. However, neither ICA nor fALFF revealed any group differences. Our findings suggest that abnormal connectivity patterns between pain-related regions and the remaining brain during rest reflect an impaired central mechanism of pain modulation in FM. Weaker coupling between pain regions and prefrontal- and sensorimotor areas might indicate a less efficient system level control of pain circuits. Moreover, our results show that multiple, complementary analytical approaches are valuable for obtaining a more comprehensive characterization of deviant resting-state activity. In conclusion, our findings show that FM primarily is associated with decreased connectivity, for example, between several pain-related areas and sensorimotor regions, which could reflect a deficiency in pain regulation.

Keywords: brain connectivity; fMRI; fibromyalgia; pain; resting-state.

Figures

FIG. 1.

Group differences in pain sensitivity. Fibromyalgia patients had lower P50 [pressure corresponding to ratings of 50 mm on a 100 mm visual analogue scale (VAS)] compared with controls [two sample t-test, t(36) = −3.98, p=0.00032]. Error bars denote standard deviations.

FIG. 2.

Differences in functional connectivity between fibromyalgia patients and a cohort of healthy subjects projected on a semitransparent template brain [p<0.00031, false discovery rate (FDR) corrected at cluster level]. Blue activations/edges represent decreased connectivity in fibromyalgia patients relative to healthy subjects. Red activations/edges represent increases in resting-state connectivity in fibromyalgia patients compared with healthy subjects. Seed-points for the connectivity analysis are marked as green spheres (for visualization purposes are the radius of the seeds doubled compared to those of the actual seeds).

FIG. 3.

Correlations between individual ratings of pain sensitivity and resting-state brain connectivity (p<0.00031, FDR corrected at cluster level). Blue activations/edges represent brain areas that showed significant positive co-variability between pain resilience (P50) and resting-state brain connectivity. Red activations/edges represent brain regions that exhibited a stronger degree of brain connectivity as a function of pain sensitivity. Seed-points for the connectivity analysis are marked as green spheres.