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.@en