Abnormalities in cortical pattern of coherence in migraine detected using ultra high-density EEG

Abstract

Individuals with migraine generally experience photophobia and/or phonophobia during and between migraine attacks. Many different mechanisms have been postulated to explain these migraine phenomena including abnormal patterns of connectivity across the cortex. The results, however, remain contradictory and there is no clear consensus on the nature of the cortical abnormalities in migraine. Here, we uncover alterations in cortical patterns of coherence (connectivity) in interictal migraineurs during the presentation of visual and auditory stimuli and during rest. We used a high-density EEG system, with 128 customized electrode locations, to compare inter- and intra-hemispheric coherence in the interictal period from 17 individuals with migraine (12 female) and 18 age- and gender-matched healthy control subjects. During presentations of visual (vertical grating pattern) and auditory (modulated tone) stimulation which varied in temporal frequency (4 and 6 Hz), and during rest, participants performed a colour detection task at fixation. Analyses included characterizing the inter- and intra-hemisphere coherence between the scalp EEG channels over 2-s time intervals and over different frequency bands at different spatial distances and spatial clusters. Pearson's correlation coefficients were estimated at zero-lag. Repeated measures analyses-of-variance revealed that, relative to controls, migraineurs exhibited significantly (i) faster colour detection performance, (ii) lower spatial coherence of alpha-band activity, for both inter- and intra-hemisphere connections, and (iii) the reduced coherence occurred predominantly in frontal clusters during both sensory conditions, regardless of the stimulation frequency, as well as during the resting-state. The abnormal patterns of EEG coherence in interictal migraineurs during visual and auditory stimuli, as well as at rest (eyes open), may be associated with the cortical hyper-responsivity that is characteristic of abnormal sensory processing in migraineurs.

Keywords: cortical coherence; high-density electroencephalography; migraine; resting state; sensory evoked potentials.

© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.

Figures

Graphical Abstract

Figure 1

Structure of auditory and visual trials. A fixation cross appeared centrally, jittered for between 1 and 1.5 s. A stimulus, either auditory or visual, was then presented for 2 s followed by a 1–1.5 s inter-stimulus-interval (ISI), consisting of a grey screen and a fixation cross. Participants pressed the spacebar whenever the cross flashed white (for 0.1 s). If they did not respond, the fixation cross turned red (for 0.1 s).

Figure 2

A 2D map of electrode locations. 10-20 electrode labels are included for reference. Coloured patterns indicate clusters used for analysis: left and right frontal, parietal, occipito-parietal, and occipital areas. Scale adjusted for illustration. Contiguous electrodes have equal vertical and horizontal inter-electrode distances (i.d.) in this 2D map.

Figure 3

Four-way coherence interaction of group×hemisphere×frequency bands×link lengths for 4 Hz stimulation frequency. Comparison of spatial coherence between individuals with migraine and controls for the visual and auditory stimulation frequency of 4 Hz as a function of link lengths for each of the five frequency bands, each of the hemisphere (inter/intra) and groups. HP-transformed spatial coherence is shown using dashed lines for controls and solid lines for migraineurs. Asterisks show the significant group differences for each link length (on the x-axis) and each frequency band (colours of asterisks are matched with the frequency bands), based on LSD (P < 0.05) post hoc test (M, migraineurs; C, controls).

Figure 4

Five-way coherence interaction of group×link lengths×spatial clusters×hemisphere×modalities for 4 Hz stimulation frequency. Comparison of spatial coherence between migraineurs and controls for the visual stimulation frequency of 4 Hz as a function of link lengths for each of the eight spatial clusters, hemisphere (intra/inter) and groups (Fig. 5 shows the results for the auditory stimulation). HP-transformed spatial coherence is shown using dashed lines for controls and solid lines for migraineurs. Asterisks show the significant group differences for each link length (on the x-axis) and each hemisphere (colours of asterisks are matched with the inter- and intra-hemisphere), based on LSD (P < 0.05) post hoc test (M, migraineurs; C, controls).

Figure 5

Five-way coherence interaction of group×link lengths×spatial clusters×hemisphere×modalities for 4 Hz stimulation frequency. Comparison of spatial coherence between migraineurs and controls for the auditory stimulation frequency of 4 Hz as a function of link lengths for each of the eight spatial clusters, hemisphere (intra/inter), and groups (Fig. 4 shows the results for the visual stimulation). HP-transformed spatial coherence is shown using dashed lines for controls and solid lines for migraineurs. Asterisks show the significant group differences for each link length (on the x-axis) and each hemisphere (colours of asterisks are matched with the inter- and intra-hemisphere), based on LSD (P < 0.05) post hoc test (M, migraineurs; C, controls).

Figure 6

Four-way coherence interaction of group×hemisphere×frequency bands×spatial clusters for 4 Hz stimulation frequency. Comparison of spatial coherence between individuals with migraine and controls for the stimulation frequency of 4 Hz as a function of frequency bands for each of the eight spatial clusters, hemisphere (intra/inter) and groups. HP-transformed spatial coherence is shown using dashed lines for controls and solid lines for migraineurs. Asterisks show the significant group differences for each frequency band (on the x-axis) and each hemisphere (colours of asterisks are matched with the inter- and intra-hemisphere), based on LSD (P < 0.05) post hoc test (M, migraineurs; C, controls).

Figure 7

Four-way resting-state coherence interaction of group×frequency bands×spatial clusters×link lengths. Comparison of spatial coherence between individuals with migraine and controls during the resting-state recording as a function of link lengths for each of the five frequency bands, each of the eight spatial clusters and groups. HP-transformed spatial coherence is shown using dashed lines for controls and solid lines for the migraine patients. Asterisks show the significant group differences for each link length (on the x-axis) and each frequency band (colours of asterisks are matched with the frequency bands), based on LSD (P < 0.05) post hoc test (M, migraineurs; C, controls).