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Fibromyalgia interacts with age to change the brain.

Ceko M, Bushnell MC, Fitzcharles MA, Schweinhardt P - Neuroimage Clin (2013)

Bottom Line: To examine their functional significance, gray matter differences were compared with experimental pain sensitivity.In both age groups, structural brain alterations were associated with experimental pain sensitivity, which was increased in older patients but normal in younger patients.These results suggest that brain structure and function shift from being adaptive in younger to being maladaptive in older patients, which might have important treatment implications.

View Article: PubMed Central - PubMed

Affiliation: Alan Edwards Centre for Research on Pain, McGill University, 3640 University Street, Montreal, Quebec H3A O7C, Canada ; Integrated Program in Neuroscience, McGilll University, 3801 University Street, Montreal Quebec H3A 2B4, Canada ; National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.

ABSTRACT
Although brain plasticity in the form of gray matter increases and decreases has been observed in chronic pain, factors determining the patterns of directionality are largely unknown. Here we tested the hypothesis that fibromyalgia interacts with age to produce distinct patterns of gray matter differences, specifically increases in younger and decreases in older patients, when compared to age-matched healthy controls. The relative contribution of pain duration was also investigated. Regional gray matter was measured in younger (n = 14, mean age 43, range 29-49) and older (n = 14; mean age 55, range 51-60) female fibromyalgia patients and matched controls using voxel-based morphometry and cortical thickness analysis of T1-weighted magnetic resonance images. To examine their functional significance, gray matter differences were compared with experimental pain sensitivity. Diffusion-tensor imaging was used to assess whether white matter changed in parallel with gray matter, and resting-state fMRI was acquired to examine whether pain-related gray matter changes are associated with altered functional connectivity. Older patients showed exclusively decreased gray matter, accompanied by compromised white matter integrity. In contrast, younger patients showed exclusively gray matter increases, namely in the basal ganglia and insula, which were independent of pain duration. Associated white matter changes in younger patients were compatible with gray matter hypertrophy. In both age groups, structural brain alterations were associated with experimental pain sensitivity, which was increased in older patients but normal in younger patients. Whereas more pronounced gray matter decreases in the posterior cingulate cortex were related to increased experimental pain sensitivity in older patients, insular gray matter increases in younger patients correlated with lower pain sensitivity, possibly indicating the recruitment of endogenous pain modulatory mechanisms. This is supported by the finding that the insula in younger patients showed functional decoupling from an important pain-processing region, the dorsal anterior cingulate cortex. These results suggest that brain structure and function shift from being adaptive in younger to being maladaptive in older patients, which might have important treatment implications.

No MeSH data available.


Related in: MedlinePlus

Relationship between pain sensitivity and structural and functional gray matter findings in older and younger patients. A) Left: In older patients the gray matter of the right PCC/SMA (posterior cingulate cortex/supplementary motor area) was negatively correlated with pain unpleasantness. Right: Extracted mean gray matter of the PCC/SMA cluster plotted against pain unpleasantness scores in older patients (red circles) and older controls (open circles). B) Left: Functional connectivity analysis of the PCC/SMA seed showed decreased resting state correlations with MPFC (medial prefrontal cortex) in older patients compared to matched controls; colorbar shows t-values for the contrast older patients < older controls; there were no significant clusters for the opposite contrast. Right: Parameter estimates (correlation values) for older controls (white bar) and older patients (red bar). C) Left: In younger patients the gray matter of the left aINS (anterior insula) was negatively correlated with pain unpleasantness (colorbar shows t-values for the whole brain VBM regression with pain unpleasantness score. Right: Extracted mean gray matter of the aINS cluster plotted against pain unpleasantness scores in younger patients (blue circles) and younger controls (open circles). D) Left: Functional connectivity analysis of the aINS seed showed decreased resting state correlations to dACC (dorsal anterior cingulate cortex) in younger patients compared to matched controls; colorbar shows t-values for the contrast younger < younger controls; there were no significant clusters for the opposite contrast. Right: Parameter estimates (correlation values) for younger controls (white bar) and younger patients (blue bar). Results are displayed on study average brain, left side of the brain is on the left; a.u., arbitrary unit.
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f0025: Relationship between pain sensitivity and structural and functional gray matter findings in older and younger patients. A) Left: In older patients the gray matter of the right PCC/SMA (posterior cingulate cortex/supplementary motor area) was negatively correlated with pain unpleasantness. Right: Extracted mean gray matter of the PCC/SMA cluster plotted against pain unpleasantness scores in older patients (red circles) and older controls (open circles). B) Left: Functional connectivity analysis of the PCC/SMA seed showed decreased resting state correlations with MPFC (medial prefrontal cortex) in older patients compared to matched controls; colorbar shows t-values for the contrast older patients < older controls; there were no significant clusters for the opposite contrast. Right: Parameter estimates (correlation values) for older controls (white bar) and older patients (red bar). C) Left: In younger patients the gray matter of the left aINS (anterior insula) was negatively correlated with pain unpleasantness (colorbar shows t-values for the whole brain VBM regression with pain unpleasantness score. Right: Extracted mean gray matter of the aINS cluster plotted against pain unpleasantness scores in younger patients (blue circles) and younger controls (open circles). D) Left: Functional connectivity analysis of the aINS seed showed decreased resting state correlations to dACC (dorsal anterior cingulate cortex) in younger patients compared to matched controls; colorbar shows t-values for the contrast younger < younger controls; there were no significant clusters for the opposite contrast. Right: Parameter estimates (correlation values) for younger controls (white bar) and younger patients (blue bar). Results are displayed on study average brain, left side of the brain is on the left; a.u., arbitrary unit.

Mentions: A voxel-wise whole brain regression of gray matter with unpleasantness ratings of the pressure stimuli revealed that of the areas that showed gray matter decreases in older patients, PCC gray matter volume was negatively correlated with pain sensitivity, i.e. patients with the least amount of gray matter were most sensitive to the experimental pressure stimuli (t = 5.32, p = 0.014, cluster size 157 voxels, MNI coordinates 3, − 19, 42; Fig. 5A). This gray matter cluster showed no significant correlation with pain catastrophizing scores (r = − 0.165, p = 0.57). To better understand the implications of reduced gray matter in the PCC, we conducted a functional connectivity analysis seeding in the PCC. This revealed decreased resting state correlations with the MPFC in older patients compared to their controls (t = 4.87, p = 0.010, cluster size 177 voxels, MNI coordinates 4, 38, − 12; Fig. 5B). No region showed significantly increased resting state correlations with the PCC in older patients. The PCC–MPFC connectivity in patients was not related to pain catastrophizing scores (r = − 0.04, p = 0.902) or the level of their pain during the resting state scan (r = − 0.04, p = 0.896).


Fibromyalgia interacts with age to change the brain.

Ceko M, Bushnell MC, Fitzcharles MA, Schweinhardt P - Neuroimage Clin (2013)

Relationship between pain sensitivity and structural and functional gray matter findings in older and younger patients. A) Left: In older patients the gray matter of the right PCC/SMA (posterior cingulate cortex/supplementary motor area) was negatively correlated with pain unpleasantness. Right: Extracted mean gray matter of the PCC/SMA cluster plotted against pain unpleasantness scores in older patients (red circles) and older controls (open circles). B) Left: Functional connectivity analysis of the PCC/SMA seed showed decreased resting state correlations with MPFC (medial prefrontal cortex) in older patients compared to matched controls; colorbar shows t-values for the contrast older patients < older controls; there were no significant clusters for the opposite contrast. Right: Parameter estimates (correlation values) for older controls (white bar) and older patients (red bar). C) Left: In younger patients the gray matter of the left aINS (anterior insula) was negatively correlated with pain unpleasantness (colorbar shows t-values for the whole brain VBM regression with pain unpleasantness score. Right: Extracted mean gray matter of the aINS cluster plotted against pain unpleasantness scores in younger patients (blue circles) and younger controls (open circles). D) Left: Functional connectivity analysis of the aINS seed showed decreased resting state correlations to dACC (dorsal anterior cingulate cortex) in younger patients compared to matched controls; colorbar shows t-values for the contrast younger < younger controls; there were no significant clusters for the opposite contrast. Right: Parameter estimates (correlation values) for younger controls (white bar) and younger patients (blue bar). Results are displayed on study average brain, left side of the brain is on the left; a.u., arbitrary unit.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814958&req=5

f0025: Relationship between pain sensitivity and structural and functional gray matter findings in older and younger patients. A) Left: In older patients the gray matter of the right PCC/SMA (posterior cingulate cortex/supplementary motor area) was negatively correlated with pain unpleasantness. Right: Extracted mean gray matter of the PCC/SMA cluster plotted against pain unpleasantness scores in older patients (red circles) and older controls (open circles). B) Left: Functional connectivity analysis of the PCC/SMA seed showed decreased resting state correlations with MPFC (medial prefrontal cortex) in older patients compared to matched controls; colorbar shows t-values for the contrast older patients < older controls; there were no significant clusters for the opposite contrast. Right: Parameter estimates (correlation values) for older controls (white bar) and older patients (red bar). C) Left: In younger patients the gray matter of the left aINS (anterior insula) was negatively correlated with pain unpleasantness (colorbar shows t-values for the whole brain VBM regression with pain unpleasantness score. Right: Extracted mean gray matter of the aINS cluster plotted against pain unpleasantness scores in younger patients (blue circles) and younger controls (open circles). D) Left: Functional connectivity analysis of the aINS seed showed decreased resting state correlations to dACC (dorsal anterior cingulate cortex) in younger patients compared to matched controls; colorbar shows t-values for the contrast younger < younger controls; there were no significant clusters for the opposite contrast. Right: Parameter estimates (correlation values) for younger controls (white bar) and younger patients (blue bar). Results are displayed on study average brain, left side of the brain is on the left; a.u., arbitrary unit.
Mentions: A voxel-wise whole brain regression of gray matter with unpleasantness ratings of the pressure stimuli revealed that of the areas that showed gray matter decreases in older patients, PCC gray matter volume was negatively correlated with pain sensitivity, i.e. patients with the least amount of gray matter were most sensitive to the experimental pressure stimuli (t = 5.32, p = 0.014, cluster size 157 voxels, MNI coordinates 3, − 19, 42; Fig. 5A). This gray matter cluster showed no significant correlation with pain catastrophizing scores (r = − 0.165, p = 0.57). To better understand the implications of reduced gray matter in the PCC, we conducted a functional connectivity analysis seeding in the PCC. This revealed decreased resting state correlations with the MPFC in older patients compared to their controls (t = 4.87, p = 0.010, cluster size 177 voxels, MNI coordinates 4, 38, − 12; Fig. 5B). No region showed significantly increased resting state correlations with the PCC in older patients. The PCC–MPFC connectivity in patients was not related to pain catastrophizing scores (r = − 0.04, p = 0.902) or the level of their pain during the resting state scan (r = − 0.04, p = 0.896).

Bottom Line: To examine their functional significance, gray matter differences were compared with experimental pain sensitivity.In both age groups, structural brain alterations were associated with experimental pain sensitivity, which was increased in older patients but normal in younger patients.These results suggest that brain structure and function shift from being adaptive in younger to being maladaptive in older patients, which might have important treatment implications.

View Article: PubMed Central - PubMed

Affiliation: Alan Edwards Centre for Research on Pain, McGill University, 3640 University Street, Montreal, Quebec H3A O7C, Canada ; Integrated Program in Neuroscience, McGilll University, 3801 University Street, Montreal Quebec H3A 2B4, Canada ; National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.

ABSTRACT
Although brain plasticity in the form of gray matter increases and decreases has been observed in chronic pain, factors determining the patterns of directionality are largely unknown. Here we tested the hypothesis that fibromyalgia interacts with age to produce distinct patterns of gray matter differences, specifically increases in younger and decreases in older patients, when compared to age-matched healthy controls. The relative contribution of pain duration was also investigated. Regional gray matter was measured in younger (n = 14, mean age 43, range 29-49) and older (n = 14; mean age 55, range 51-60) female fibromyalgia patients and matched controls using voxel-based morphometry and cortical thickness analysis of T1-weighted magnetic resonance images. To examine their functional significance, gray matter differences were compared with experimental pain sensitivity. Diffusion-tensor imaging was used to assess whether white matter changed in parallel with gray matter, and resting-state fMRI was acquired to examine whether pain-related gray matter changes are associated with altered functional connectivity. Older patients showed exclusively decreased gray matter, accompanied by compromised white matter integrity. In contrast, younger patients showed exclusively gray matter increases, namely in the basal ganglia and insula, which were independent of pain duration. Associated white matter changes in younger patients were compatible with gray matter hypertrophy. In both age groups, structural brain alterations were associated with experimental pain sensitivity, which was increased in older patients but normal in younger patients. Whereas more pronounced gray matter decreases in the posterior cingulate cortex were related to increased experimental pain sensitivity in older patients, insular gray matter increases in younger patients correlated with lower pain sensitivity, possibly indicating the recruitment of endogenous pain modulatory mechanisms. This is supported by the finding that the insula in younger patients showed functional decoupling from an important pain-processing region, the dorsal anterior cingulate cortex. These results suggest that brain structure and function shift from being adaptive in younger to being maladaptive in older patients, which might have important treatment implications.

No MeSH data available.


Related in: MedlinePlus