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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

White matter findings in fibromyalgia patients. A) Older patients had decreased FA compared to matched controls in the corpus callosum adjacent to the right PCC (posterior cingulate cortex). The significant FA cluster controlling for age (older patients < older controls; red, p < 0.05 corrected) is displayed in the ROI mask (yellow). There were no significant clusters for the opposite contrast. B) Younger patients had marginally increased FA compared to matched controls in the anterior thalamic radiation/anterior limb of the internal capsule medial to the left putamen. The FA cluster controlling for age (younger patients > younger controls; blue, p = 0.058 corrected) is displayed in the ROI mask (yellow). There were no significant (or near significant) clusters for the opposite contrast. C) Affected white matter tracts in older (left) and younger (right) patients. Colorbar shows the percentage of subjects who share a common pathway. D) Axial diffusivity was significantly lower in older patients compared to matched controls (ANOVA controlling for age; F = 5.85, p = 0.024), radial diffusivity was significantly higher (F = 7.71, p = 0.011) and there was no significant group difference in mean diffusivity (F = 0.32, p = 0.581). E) Mean and radial diffusivities were significantly lower in younger patients compared to matched controls (ANOVA controlling for age; mean diff., F = 5.05, p = 0.033; radial, F = 5.31, p = 0.029), with no significant group difference in axial diffusivity (F = 0.832, 0.370). Results are displayed on the study average brain; left side of the brain is on the left. Bars represent mean in controls (white) and patients (black), error bars represent SD.
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f0015: White matter findings in fibromyalgia patients. A) Older patients had decreased FA compared to matched controls in the corpus callosum adjacent to the right PCC (posterior cingulate cortex). The significant FA cluster controlling for age (older patients < older controls; red, p < 0.05 corrected) is displayed in the ROI mask (yellow). There were no significant clusters for the opposite contrast. B) Younger patients had marginally increased FA compared to matched controls in the anterior thalamic radiation/anterior limb of the internal capsule medial to the left putamen. The FA cluster controlling for age (younger patients > younger controls; blue, p = 0.058 corrected) is displayed in the ROI mask (yellow). There were no significant (or near significant) clusters for the opposite contrast. C) Affected white matter tracts in older (left) and younger (right) patients. Colorbar shows the percentage of subjects who share a common pathway. D) Axial diffusivity was significantly lower in older patients compared to matched controls (ANOVA controlling for age; F = 5.85, p = 0.024), radial diffusivity was significantly higher (F = 7.71, p = 0.011) and there was no significant group difference in mean diffusivity (F = 0.32, p = 0.581). E) Mean and radial diffusivities were significantly lower in younger patients compared to matched controls (ANOVA controlling for age; mean diff., F = 5.05, p = 0.033; radial, F = 5.31, p = 0.029), with no significant group difference in axial diffusivity (F = 0.832, 0.370). Results are displayed on the study average brain; left side of the brain is on the left. Bars represent mean in controls (white) and patients (black), error bars represent SD.

Mentions: Whole-brain analysis yielded no significant group differences in white matter FA in the older fibromyalgia patients compared to matched controls. In the ROI analysis focusing on white matter adjacent to the regions with gray matter decreases (bilateral ACC/MPFC, left VLPFC, right DLPFC, right PMC, right PCC), older patients had significantly decreased FA compared to their controls adjacent to the PCC (corpus callosum, t = 4.11, p = 0.041, cluster size 43 voxels, MNI coordinates at peak 17, − 16, 35, Fig. 3A). The FA decrease was caused by a significant decrease in axial diffusivity (F = 5.85, p = 0.024) and increase in radial diffusivity (F = 7.72, p = 0.011) (Fig. 3D). Mean diffusivity did not differ significantly between groups (F = 0.31, p = 0.581). We next used probabilistic tractography to determine the connectivity of the corpus callosum region with decreased FA, and identified connections to motor/premotor cortex, an area where older patients had decreased gray matter. Here, the identified white matter pathway merged with the corticospinal tract (Fig. 3C, left). No region showed a significant FA increase in older patients.


Fibromyalgia interacts with age to change the brain.

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

White matter findings in fibromyalgia patients. A) Older patients had decreased FA compared to matched controls in the corpus callosum adjacent to the right PCC (posterior cingulate cortex). The significant FA cluster controlling for age (older patients < older controls; red, p < 0.05 corrected) is displayed in the ROI mask (yellow). There were no significant clusters for the opposite contrast. B) Younger patients had marginally increased FA compared to matched controls in the anterior thalamic radiation/anterior limb of the internal capsule medial to the left putamen. The FA cluster controlling for age (younger patients > younger controls; blue, p = 0.058 corrected) is displayed in the ROI mask (yellow). There were no significant (or near significant) clusters for the opposite contrast. C) Affected white matter tracts in older (left) and younger (right) patients. Colorbar shows the percentage of subjects who share a common pathway. D) Axial diffusivity was significantly lower in older patients compared to matched controls (ANOVA controlling for age; F = 5.85, p = 0.024), radial diffusivity was significantly higher (F = 7.71, p = 0.011) and there was no significant group difference in mean diffusivity (F = 0.32, p = 0.581). E) Mean and radial diffusivities were significantly lower in younger patients compared to matched controls (ANOVA controlling for age; mean diff., F = 5.05, p = 0.033; radial, F = 5.31, p = 0.029), with no significant group difference in axial diffusivity (F = 0.832, 0.370). Results are displayed on the study average brain; left side of the brain is on the left. Bars represent mean in controls (white) and patients (black), error bars represent SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f0015: White matter findings in fibromyalgia patients. A) Older patients had decreased FA compared to matched controls in the corpus callosum adjacent to the right PCC (posterior cingulate cortex). The significant FA cluster controlling for age (older patients < older controls; red, p < 0.05 corrected) is displayed in the ROI mask (yellow). There were no significant clusters for the opposite contrast. B) Younger patients had marginally increased FA compared to matched controls in the anterior thalamic radiation/anterior limb of the internal capsule medial to the left putamen. The FA cluster controlling for age (younger patients > younger controls; blue, p = 0.058 corrected) is displayed in the ROI mask (yellow). There were no significant (or near significant) clusters for the opposite contrast. C) Affected white matter tracts in older (left) and younger (right) patients. Colorbar shows the percentage of subjects who share a common pathway. D) Axial diffusivity was significantly lower in older patients compared to matched controls (ANOVA controlling for age; F = 5.85, p = 0.024), radial diffusivity was significantly higher (F = 7.71, p = 0.011) and there was no significant group difference in mean diffusivity (F = 0.32, p = 0.581). E) Mean and radial diffusivities were significantly lower in younger patients compared to matched controls (ANOVA controlling for age; mean diff., F = 5.05, p = 0.033; radial, F = 5.31, p = 0.029), with no significant group difference in axial diffusivity (F = 0.832, 0.370). Results are displayed on the study average brain; left side of the brain is on the left. Bars represent mean in controls (white) and patients (black), error bars represent SD.
Mentions: Whole-brain analysis yielded no significant group differences in white matter FA in the older fibromyalgia patients compared to matched controls. In the ROI analysis focusing on white matter adjacent to the regions with gray matter decreases (bilateral ACC/MPFC, left VLPFC, right DLPFC, right PMC, right PCC), older patients had significantly decreased FA compared to their controls adjacent to the PCC (corpus callosum, t = 4.11, p = 0.041, cluster size 43 voxels, MNI coordinates at peak 17, − 16, 35, Fig. 3A). The FA decrease was caused by a significant decrease in axial diffusivity (F = 5.85, p = 0.024) and increase in radial diffusivity (F = 7.72, p = 0.011) (Fig. 3D). Mean diffusivity did not differ significantly between groups (F = 0.31, p = 0.581). We next used probabilistic tractography to determine the connectivity of the corpus callosum region with decreased FA, and identified connections to motor/premotor cortex, an area where older patients had decreased gray matter. Here, the identified white matter pathway merged with the corticospinal tract (Fig. 3C, left). No region showed a significant FA increase in older patients.

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