Investigation of cortical thickness and volume during spontaneous attacks of migraine without aura: a 3-Tesla MRI study

Faisal Mohammad Amin, Roberto De Icco, Mohammad Al-Mahdi Al-Karagholi, Jayachandra M Raghava, Frauke Wolfram, Henrik B W Larsson, Messoud Ashina, Faisal Mohammad Amin, Roberto De Icco, Mohammad Al-Mahdi Al-Karagholi, Jayachandra M Raghava, Frauke Wolfram, Henrik B W Larsson, Messoud Ashina

Abstract

Background: Structural imaging has revealed changes in cortical thickness in migraine patients compared to healthy controls is reported, but presence of dynamic cortical and subcortical changes during migraine attack versus inter-ictal phase is unknown. The aim of the present study was to investigate possible changes in cortical thickness during spontaneous migraine attacks. We hypothesized that pain-related cortical area would be affected during the attack compared to an inter-ictal phase.

Methods: Twenty-five patients with migraine without aura underwent three-dimensional T1-weighted imaging on a 3-Tesla MRI scanner during spontaneous and untreated migraine attacks. Subsequently, 20 patients were scanned in the inter-ictal phase, while 5 patients did not show up for the inter-ictal scan. Four patients were excluded from the analysis because of bilateral migraine pain and another one patient was excluded due to technical error in the imaging. Longitudinal image processing was done using FreeSurfer. Repeated measures ANOVA was used for statistical analysis and to control for multiple comparison the level of significance was set at p = 0.025.

Results: In a total of 15 patients, we found reduced cortical thickness of the precentral (p = 0.023), pericalcarine (p = 0.024), and temporal pole (p = 0.017) cortices during the attack compared to the inter-ictal phase. Cortical volume was reduced in prefrontal (p = 0.018) and pericalcarine (p = 0.017) cortices. Hippocampus volume was increased during attack (p = 0.007). We found no correlations between the pain side or any other clinical parameters and the reduced cortical size.

Conclusion: Spontaneous migraine attacks are accompanied by transient reduced cortical thickness and volume in pain-related areas. The findings constitute a fingerprint of acute pain in migraine patients, which can be used as a possible biomarker to predict antimigraine treatment effect in future studies.

Trial registration: The study was registered at ClinicalTrials.gov ( NCT02202486 ).

Keywords: Cortical volume; Migraine attack; Migraine brain; Migraine cortex; Pain cortex.

Conflict of interest statement

FMA has received lecturing fee and/or served as advisory board member for Teva, Lundbeck, Eli Lilly and Novartis. FMA is principal investigator for phase 4 trials for Novartis and Teva.

RDI reported no conflicts of interests.

MAK reports no conflicts of interests.

JMR reports no conflicts of interests.

FW reports no conflicts of interests.

HBWL reports no conflicts of interests.

MA reports receiving consulting fees and advisory boards fees from Alder, Allergan, Amgen, Eli Lilly, Lundbeck, Novartis, and Teva, fees for serving as a principal investigator, paid to his institution, from Alder, Allergan, Amgen, Electro-Core, Eli Lilly, Lundbeck, Novartis, and Teva, and grant support, paid to his institution, from Novo Nordisk Foundation, Novartis, and Lundbeck Foundation.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Comparison of precentral cortex thickness and volume between S1 and S2 scans. Legend: S1: MRI scan performed during spontaneous migraine attack; S2: MRI scan performed during inter-ictal period; PAIN side refers to the side of spontaneous migraine attack recorded at T1. Panel A: thickness of precentral cortex was significantly lower during S1 (factor SESSION: p = 0.023), without significant association with the pain side (factor SIDE: p = 0.434, interaction SESSIONxSIDE: p = 0.515). Panel B: volume of precentral cortex was significantly lower during S1 (factor SESSION: p = 0.018), without significant association with the pain side (factor SIDE: p = 0.497, interaction SESSIONxSIDE: p = 0.276)
Fig. 2
Fig. 2
Comparison of pericalcarine cortex thickness and volume between S1 and S2 scans. Legend: S1: MRI scan performed during spontaneous migraine attack; S2: MRI scan performed during inter-ictal period; PAIN side refers to the side of spontaneous migraine attack recorded at T1. Panel A: thickness of pericalcarine cortex was significantly lower during S1 (factor SESSION: p = 0.024), without significant association with the pain side (factor SIDE: p = 0.923, interaction SESSIONxSIDE: p = 0.860). Panel B: volume of pericalcarine cortex was significantly lower during S1 (factor SESSION: p = 0.017), without significant association with the pain side (factor SIDE: p = 0.977, interaction SESSIONxSIDE: p = 0.833)

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