Functional and structural MRI signature of the induced migraine attack

Magnetic resonance imaging (MRI) studies have consistently shown a distributed pattern of static and dynamic functional brain alterations in migraine patients. Up to now, it is elusive whether these alterations may represent a migraine-specific or phase-specific modification occurring along the migraine cyclical experience. This study aims to assess the functional and microstructural alteration of the grey matter which characterize the brain of people living with migraine compared with a matched group of healthy subjects, particularly during the activation derived from an induced attack by nitroglycerin (NTG) administration. Ten subjects suffering from episodic migraine without aura (EM, 5 female, 28,9 yo, 4,4 migraine days per month) underwent 3T MRI examinations consisting of four task-free functional MRI (fMRI) and T13D scan repetitions during the subsequent phases of a nitroglycerin-induced migraine attack (baseline, prodrome, full-blown attack, recovery). Ten healthy subjects (HS, 4 female, 26.9 yo) were enrolled for reference as control and underwent the same pharmacological protocol. A non-parametric permutation test was run to detect significant functional connectivity (FC) changes between EM and HS subjects in the different attack phases. Secondly, a seed-based analysis (SCA) and a wavelet component analysis (WCA) were performed to focus the attention on the static and dynamic altered relationship between the thalamus and the rest of the brain, over the migraine experience. Moreover, 3D-T1 images were processed to obtain subject-specific GM density (GMd) maps. A non-parametric permutation test was run to detect significant GMd differences in EM compared to HS during the attack phases. Finally, fMRI data were tested for correlations with the clinical variables collected. At baseline, EM subjects showed a constitutively significantly altered FC within the posterior cerebellum, frontal/prefrontal cortex and cingulate cortex. The thalamus instead, express its pivotal role since the prodromal phase, exhibiting an altered coupling with the brainstem, the cingulate cortex and the posterior part of the cerebellum over the course of the migraine cycle. WCA showed instead a loss of synchronisation between the thalami and the salience network, mainly occurring during the prodrome and full-blown phases. These findings further support the idea that a temporal change in thalamic function occurs over the experimentally induced phases of NTG-induced headache in migraine patients. From a structural point of view, EM subjects showed significantly reduced GMd in the insula, inferior parietal lobe, and superior and middle temporal gyrus, compared to healthy subjects. An increased density is instead observed in the cingulate cortex, middle frontal gyrus and the limbic system, but it does not significantly vary along the migraine attack experience. The findings observed suggest a baseline alteration in descending modulation pain processing in migraine. Migraine-like pain induction caused a profound alteration of the FC, which persisted over recovery. The results also point to the involvement of the cerebellum - a multiple effector system integrator and a ruler of pain perception modulation – and the frontal/prefrontal cortex. These involvements are not only correlated with pain intensity and migraine frequency but are also suggestive of the cognitive impairment associated with the migraine ictal phase. Finally, the microstructural modification here discussed suggests that migraine is associated with significant GM volume loss in key areas for pain processing, possibly reflecting alterations in the local dendritic complexity caused by the disease.

Magnetic resonance imaging (MRI) studies have consistently shown a distributed pattern of static and dynamic functional brain alterations in migraine patients. Up to now, it is elusive whether these alterations may represent a migraine-specific or phase-specific modification occurring along the migraine cyclical experience. This study aims to assess the functional and microstructural alteration of the grey matter which characterizes the brain of people living with migraine compared with a matched group of healthy subjects, particularly during the activation derived from an attack induced by nitroglycerin (NTG) administration. Ten subjects suffering from episodic migraine without aura (EM, 5 female, 28,9 years old, 4.4 migraine days per month) underwent 3T MRI examinations consisting of four task-free functional MRI (fMRI) and T13D scan repetitions during subsequent phases of a nitroglycerin-induced migraine attack (baseline, prodrome, full-blown attack, recovery). Ten healthy subjects (HS, 4 female, 26.9 yo) were enrolled for reference as control and underwent the same pharmacological protocol. A non-parametric permutation test was run to detect significant functional connectivity (FC) changes between EM and HS subjects in the different attack phases. Secondly, a seed-based correlation analysis (SCA) and a wavelet component analysis (WCA) were performed to focus the attention on the static and dynamic altered relationship between the thalamus and the rest of the brain, during the different phases of the migraine attack. Moreover, 3D-T1 images were processed to obtain subject-specific GM density (GMd) maps. A non-parametric permutation test was run to detect significant GMd differences in EM compared to HS during the attack phases. Finally, fMRI data were tested for correlations with the clinical variables collected. At baseline, EM subjects showed a significantly altered FC within the posterior cerebellum, frontal/prefrontal cortex, and cingulate cortex. The thalamus, instead, expressed its pivotal role from the prodromal phase, exhibiting an altered coupling with the brainstem, the cingulate cortex, and the cerebellum's posterior part over the migraine cycle. Moreover, WCA proved a loss of synchronisation between the thalami and the salience network, observed mainly during the prodrome and full-blown phases. These findings further support the idea that a temporal change in thalamic function occurs over the experimentally induced phases of NTG-induced headache in migraine patients. From a structural point of view, EM subjects showed significantly reduced GMd in the insula, inferior parietal lobe, and superior and middle temporal gyrus, compared to healthy subjects. An increased density was instead observed in the cingulate cortex, middle frontal gyrus and the limbic system, but it did not significantly change during the different phases of the attack. Migraine-like pain induction caused a profound alteration of the FC, which persisted over recovery. The results point to the involvement of the cerebellum - a multiple effector system integrator and a ruler of pain perception modulation – and the frontal/prefrontal cortex. The changes observed in these areas may also explain the cognitive impairment associated with the migraine ictal phase. Finally, the microstructural modification here discussed suggests that migraine is associated with significant GM volume loss in key areas for pain processing, possibly reflecting alterations in the local dendritic complexity caused by the disease.