Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy

P Flodin, S Martinsen, K Mannerkorpi, M Löfgren, I Bileviciute-Ljungar, E Kosek, P Fransson, P Flodin, S Martinsen, K Mannerkorpi, M Löfgren, I Bileviciute-Ljungar, E Kosek, P Fransson

Abstract

Physical exercise is one of the most efficient interventions to mitigate chronic pain symptoms in fibromyalgia (FM). However, little is known about the neurophysiological mechanisms mediating these effects. In this study we investigated resting-state connectivity using functional magnetic resonance imaging (fMRI) before and after a 15 week standardized exercise program supervised by physical therapists. Our aim was to gain an understanding of how physical exercise influences previously shown aberrant patterns of intrinsic brain activity in FM. Fourteen FM patients and eleven healthy controls successfully completed the physical exercise treatment. We investigated post- versus pre-treatment changes of brain connectivity, as well as changes in clinical symptoms in the patient group. FM patients reported improvements in symptom severity. Although several brain regions showed a treatment-related change in connectivity, only the connectivity between the right anterior insula and the left primary sensorimotor area was significantly more affected by the physical exercise among the fibromyalgia patients compared to healthy controls. Our results suggest that previously observed aberrant intrinsic brain connectivity patterns in FM are partly normalized by the physical exercise therapy. However, none of the observed normalizations in intrinsic brain connectivity were significantly correlated with symptom changes. Further studies conducted in larger cohorts are warranted to investigate the precise relationship between improvements in fibromyalgia symptoms and changes in intrinsic brain activity.

Keywords: FIQ, Fibromyalgia Impact Questionnaire; FM, fibromyalgia; Fibromyalgia; Functional connectivity; PAG, periaqueductal grey; Physical exercise; Resting state fMRI; SF36BP, bodily pain subscale of the Short Form Health Survey.

Figures

Supplementary Fig. S1
Supplementary Fig. S1
Whole brain connectivity maps of the five investigated seed regions at baseline. Maps are thresholded at cluster level significance of p 

Fig. 1

Average FIQ and SF36BP ratings…

Fig. 1

Average FIQ and SF36BP ratings in 14 FM patients before (solid bars) and…

Fig. 1
Average FIQ and SF36BP ratings in 14 FM patients before (solid bars) and following (striped bars) the exercise intervention. The reduction in FIQ ratings indicates reduced FM symptoms. No change was observed in pain ratings (SF36BP). The asterisk sign (*) signifies a significant difference at p 

Fig. 2

Physical exercise induced normalization of…

Fig. 2

Physical exercise induced normalization of resting state connectivity between the right insula and…

Fig. 2
Physical exercise induced normalization of resting state connectivity between the right insula and the left sensorimotor region in the FM cohort. (A) Intrinsic connectivity between a spherical seed region (radius = 4 mm) located in the right anterior insula and a cluster extending 1490 voxels in the left sensorimotor cortex. (B) Post- versus pre-treatment insular-sensorimotor connectivity (arbitrary units) for fibromyalgia (blue) and controls (red). Error bars denote standard deviations.
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Fig. 1
Fig. 1
Average FIQ and SF36BP ratings in 14 FM patients before (solid bars) and following (striped bars) the exercise intervention. The reduction in FIQ ratings indicates reduced FM symptoms. No change was observed in pain ratings (SF36BP). The asterisk sign (*) signifies a significant difference at p 

Fig. 2

Physical exercise induced normalization of…

Fig. 2

Physical exercise induced normalization of resting state connectivity between the right insula and…

Fig. 2
Physical exercise induced normalization of resting state connectivity between the right insula and the left sensorimotor region in the FM cohort. (A) Intrinsic connectivity between a spherical seed region (radius = 4 mm) located in the right anterior insula and a cluster extending 1490 voxels in the left sensorimotor cortex. (B) Post- versus pre-treatment insular-sensorimotor connectivity (arbitrary units) for fibromyalgia (blue) and controls (red). Error bars denote standard deviations.
Fig. 2
Fig. 2
Physical exercise induced normalization of resting state connectivity between the right insula and the left sensorimotor region in the FM cohort. (A) Intrinsic connectivity between a spherical seed region (radius = 4 mm) located in the right anterior insula and a cluster extending 1490 voxels in the left sensorimotor cortex. (B) Post- versus pre-treatment insular-sensorimotor connectivity (arbitrary units) for fibromyalgia (blue) and controls (red). Error bars denote standard deviations.

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