Right fronto-insular white matter tracts link cognitive reserve and pain in migraine patients

BACKGROUND: Structural white matter abnormalities in pain-modulating, regions are present in migraine. Whether they are associated with pain chronification and with cognitive reserve is unclear. METHODS: Prospective, cohort, six-month study of adult patients with episodic or chronic migraine, and controls. Cognitive reserve, quality of life, impact of pain on daily living, depression and anxiety were assessed. Participants underwent a diffusion-tensor MRI to establish the integrity of white matter tracts of three regions of interest (ROIs) implicated in pain modulation, emotion, cognition and resilience (anterior insula, anterior cingulate gyrus, and uncinate fasciculus). RESULTS: Fifty-two individuals were enrolled: 19 episodic migraine patients, 18 chronic migraine patients, and 15 controls. The analysis of the fractional anisotropy in the ROIs showed that those patients with the poorest prognosis (i.e., those with chronic migraine despite therapy at six months -long-term chronic migraneurs) had a significantly lower fractional anisotropy in the right ROIs. Participants with higher cognitive reserve also had greater fractional anisotropy in the right anterior insula and both cingulate gyri. Multivariate analysis showed a significant association between cognitive reserve, migraine frequency, and fractional anisotropy in the right-sided regions of interest. CONCLUSIONS: Long-term chronic migraine patients show abnormalities in anterior white matter tracts, particularly of the right hemisphere, involved in pain modulation emotion, cognition and resilience. Robustness in these areas is associated with a higher cognitive reserve, which in turn might result in a lower tendency to migraine chronification.