Introduction: Migraine is associated with enhanced visual sensitivity during and outside attacks. Processing of visual information is a highly non-linear process involving complex interactions across (sub)cortical networks. In this exploratory study, we combined electroencephalography with bi-sinusoidal light stimulation to assess non-linear features of visual processing in participants with migraine.

Methods: Twenty participants with migraine (10 with aura, 10 without aura) and ten non-headache controls were measured (outside attacks). Participants received bi-sinusoidal 13 + 23 Hz red light visual stimulation. Electroencephalography spectral power and multi-spectral phase coherence were compared between groups at the driving stimulation frequencies together with multiples and combinations of these frequencies (harmonic and intermodulation frequencies) caused by non-linearities.

Results: Only at the driving frequency of 13 Hz higher spectral power was found in migraine with aura participants compared with those with migraine without aura and controls. Differences in phase coherence were present for 2nd, 4th, and 5th-order non-linearities in those with migraine (migraine with and without aura) compared with controls. Bi-sinusoidal light stimulation revealed evident non-linearities in the brain’s electroencephalography response up to the 5th order with reduced phase coherence for higher order interactions in interictal participants with migraine.

Discussion: Insight into interictal non-linear visual processing may help understand brain dynamics underlying migraine attack susceptibility. Future research is needed to determine the clinical value of the results.

Objectives: Visual system abnormalities in migraine are linked to symptoms like photophobia and the visual aura. Little is known about the mechanisms contributing to these visual system alterations. Processing of visual input by the brain is a highly nonlinear operation, involving complex interactions among cortical and subcortical neuronal networks. Timing of this process can be estimated by analysing the cortical response to external light input at different frequencies. Using a sum-of-sinusoid light signal, instead of the classic pulse train, as input and novel EEG analyses it is possible to assess the time delay and frequency domain response. Here we investigate nonlinear visual processing in subgroups of migraine patients and headache-free participants.

Methods: Migraine patients with aura, without aura and healthy participants (N = 10/group) were subjected to bi-sinusoidal light stimulation for 320 1 sec-epochs, while scalp EEG was recorded at the occipital, parietal and frontal lobes. Light stimulus frequencies were chosen to guarantee no overlap of their harmonic and intermodulation frequencies for different orders of nonlinearity. Nonlinear interactions and time delay from stimulus to cortical EEG response were analysed in the frequency domain using novel phase clustering measures and amplitude spectral measures.

Results: Higher harmonic and intermodulation interactions were detected between visual input and cortical responses. Amplitude spectrum and phase clustering responses differed per order and group. Migraine patients with aura showed a decreased time delay only at the occipital lobe compared to healthy controls and migraine patients without aura.

Conclusion: Visual processing is altered in migraine patients with aura compared to healthy controls and patients without aura. Furthermore, we demonstrated the potential of quantifying nonlinear interactions and temporal dynamics in the visual system using sum-of-sinusoid light stimulation. We are able to uncover alterations in visual processing in the context of neurological disease.