To quantitatively assess cortical dysfunction in pediatric migraine, 31 adolescents with acute migraine and age- and gender-matched controls were studied using a magnetoencephalography (MEG) system at a sampling rate of 6,000 Hz. Neuromagnetic brain activation was elicited by a finger-tapping task. The spectral and spatial signatures of magnetoencephalography data in 5 to 2,884 Hz were analyzed using Morlet wavelet and beamformers. Compared with controls, 31 migraine subjects during their headache attack phases (ictal) showed significantly prolonged latencies of neuromagnetic activation in 5 to 30 Hz, increased spectral power in 100 to 200 Hz, and a higher likelihood of neuromagnetic activation in the supplementary motor area, the occipital and ipsilateral sensorimotor cortices, in 2,200 to 2,800 Hz. Of the 31 migraine subjects, 16 migraine subjects during their headache-free phases (interictal) showed that there were no significant differences between interictal and control MEG data except that interictal spectral power in 100 to 200 Hz was significantly decreased. The results demonstrated that migraine subjects had significantly aberrant ictal brain activation, which can normalize interictally. The spread of abnormal ictal brain activation in both low- and high-frequency ranges triggered by movements may play a key role in the cascade of migraine attacks. Perspective This is the first study focusing on the spectral and spatial signatures of cortical dysfunction in adolescents with migraine using MEG signals in a frequency range of 5 to 2,884 Hz. This analyzing aberrant brain activation may be important for developing new therapeutic interventions for migraine in the future.

The cerebral cortex serves a primary role in the pathogenesis of migraine. This aberrant brain activation in migraine can be noninvasively detected with magnetoencephalography (MEG). The objective of this study was to investigate the differences in motor cortical activation between attacks (ictal) and pain free intervals (interictal) in children and adolescents with migraine using both low- and high-frequency neuromagnetic signals. Thirty subjects with an acute migraine and 30 subjects with a history of migraine, while pain free, were compared to age- and gender-matched controls using MEG. Motor cortical activation was elicited by a standardized, validated finger-tapping task. Low-frequency brain activation (1∼50 Hz) was analyzed with waveform measurements and high-frequency oscillations (65–150 Hz) were analyzed with wavelet-based beamforming. MEG waveforms showed that the ictal latency of low-frequency brain activation was significantly delayed as compared with controls, while the interictal latency of brain activation was similar to that of controls. The ictal amplitude of low-frequency brain activation was significantly increased as compared with controls, while the interictal amplitude of brain activation was similar to that of controls. The ictal source power of high-frequency oscillations was significantly stronger than that of the controls, while the interictal source power of high-frequency oscillations was significantly weaker than that of controls. The results suggest that aberrant low-frequency brain activation in migraine during a headache attack returned to normal interictally. However, high-frequency oscillations changed from ictal hyper-activation to interictal hypo-activation. Noninvasive assessment of cortical abnormality in migraine with MEG opens a new window for developing novel therapeutic strategies for childhood migraine by maintaining a balanced cortical excitability.

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To investigate the spatial heterogeneity of cortical excitability in adolescents with migraine, magnetoencephalography (MEG) recordings at a sampling rate of 6000 Hz were obtained from 35 adolescents with an acute migraine and 35 age- and gender-matched healthy controls during an auditory-motor task. Neuromagnetic activation from low- to high-frequency ranges (5–1,000 Hz) was measured at both sensor and source levels. The heterogeneity of cortical excitability was quantified within each functional modality (auditory vs. motor) and hemispherical lateralization. MEG data showed that high-frequency, not low-frequency neuromagnetic signals, revealed heterogeneous cortical activation in migraine subjects as compared with controls (p < 0.001). The alteration of the heterogeneity of cortical excitability in migraine was independent of age and gender. The degree of the neuromagnetic heterogeneity of cortical activation was significantly correlated with headache frequency (r=0.71, p < 0.005). The alteration of cortical excitability in migraine is spatially heterogeneous and frequency dependent, which has not previously been reported. The finding may be critical for developing spatially targeted therapeutic strategies for normalizing cortical excitability with the purpose of reducing headache attacks. Perspective This article presents a new approach to quantitatively measuring the spatial heterogeneity of cortical excitability in adolescents with migraine using MEG signals in a frequency range of 5–1000 Hz. The characteristics of the location and degree of cortical excitability may be critical for spatially targeted treatment for migraine.