Study Finds Monthly Migraine Days Associated With Disturbed Structural Network Integrity

Compared with healthy controls (HC), patients with episodic migraine (EM) and patients with chronic migraine (CM) exhibited differing structural brain network characteristics, potentially indicating maladaptive reorganizations of headache-related brain circuits which could lead to migraine attacks or secondary alterations to pain. Study findings were published in The Journal of Headache and Pain.

Several previous studies have reported differing functional brain altercations and multi-regional volumetric alterations in white matter and gray matter between patients with EM and CM.

“Regarding the spatial locations of migraine-related gray matter volume (GMV) changes, previous studies reported alterations in the occipital, frontal temporal cortex, somatosensory, parietal cortex and cerebellar regions,” researchers wrote. “Similarly, other studies demonstrated altered cortical thickness (CT) in migraineurs compared to controls, seen in the visual cortex, somatosensory cortex, frontal cortex, and temporo-parietal cortex.”

However, to assess the inter-relation between brain regions on a network level, a different analysis framework that moves away from regional GMV and CT differences is required, authors explained. “This approach would allow relating GMV connectedness and integrity to symptom severity (i.e., EM and CM) and would thus allow a systematic and integrative way to analyze structural abnormalities in patients with migraine.”

In the current study, researchers examined cortical and subcortical morphometric changes leading to brain network reorganization in patients with EM (n = 17) and CM (n = 12) relative to HC (n = 19) between December 2013 and July 2015. Of the patients with CM, 6 fulfilled criteria for medication overuse headache (MOH). Any patients exhibiting comorbid tension-type headache, severe psychiatric disorders, cardiac problems, or other headache or neurologic disorders were excluded from the analysis.

In addition, “all participants completed prospective headache diaries, the Migraine Disability Assessment (MIDAS) and Hamilton Anxiety (HADS-A) and Depression (HADS-D) Score questionnaires.” Patients were also free from migraine attacks at least 48 hours before and after undergoing whole-brain magnetic resonance imaging (MRI). Researchers used network-based statistics (NBS) to assess differences in the inter-regional connectivity between groups.

Analyses revealed:

• NBS showed significantly lower interregional connectivity strength between anatomical compartments including the frontotemporal, parietal and visual areas in EM and CM when compared to HC
• Higher assortativity was seen in both patient groups, with higher modularity for CM and higher transitivity for EM compared to HC
• For subcortical networks, higher assortativity and transitivity were observed for both patient groups with higher modularity for CM
• Support vector machines regression (SVR) showed network measures could robustly predict clinical parameters for migraineurs
• Patients with CM showed a thicker CT compared to HC but both EM and CM showed increases in CT, especially in visual brain regions (left occipital cortex, lingual gyrus)

“This study reported group differences in structural networks based on CT between HC, EM, and CM,” authors wrote. “Significant group differences were found in various graph theory measures and these measures were able to predict the clinical scores MIDAS and migraine attacks per month.”

Stronger alterations in the right caudate, left thalamus, left accumbens area, and right hippocampus were seen among patients with CM compared with those with EM, indicating CM impairs structural network integrity on the cortical and subcortical levels.

Furthermore, the finding “differentiating EM and CM based on association of CT and headache attacks observed in left insula underlines (a) the validity of CT as a structural marker to differentiate migraine subgroups and (b) the role of the salience network in migraine,” researchers said.

As many patients did not know their specific disease duration, investigators were unable to examine the link between network alterations and patients’ disease duration, marking a limitation to the study. The study’s sample size was also limited.

“We found a systematic increase in impairment on structural integrity with the presence of migraine attacks, indicating that CM caused the strongest structural abnormalities compared to HC and EM,” authors concluded. “The results present a significant basis for the network measures observed and gives a more enhanced tool for understanding the migraine pathophysiology.”

Reference

Michels L, Koirala N, Groppa S, et al. Structural brain network characteristics in patients with episodic and chronic migraine. J Headache Pain. Published online March 3, 2021. doi:10.1186/s10194-021-01216-8