Migraine is among the most common and debilitating neurological disorders typically affecting people of working age. It is characterised by a unilateral, pulsating headache often associated with severe pain. Despite the intensive research, there is still little understanding of the pathophysiology of migraine. At the electrophysiological level, altered oscillatory parameters have been reported within the alpha and gamma bands. At the molecular level, altered glutamate and GABA concentrations have been reported. However, there has been little cross-talk between these lines of research. Thus, the relationship between oscillatory activity and neurotransmitter concentrations remains to be empirically traced. Importantly, how these indices link back to altered sensory processing has to be clearly established as yet. Accordingly, pharmacologic treatments have been mostly symptom-based, and yet sometimes proving ineffective in resolving pain or related issues. This review provides an integrative theoretical framework of excitation–inhibition imbalance for the understanding of current evidence and to address outstanding questions concerning the pathophysiology of migraine. We propose the use of computational modelling for the rigorous formulation of testable hypotheses on mechanisms of homeostatic imbalance and for the development of mechanism-based pharmacological treatments and neurostimulation interventions.

This review describes the subjective experience of visual aura in migraine, outlines theoretical models of this phenomenon, and explores how these may be linked to neurochemical, electrophysiological, and psychophysical differences in sensory processing that have been reported in migraine with aura. Reaction–diffusion models have been used to model the hallucinations thought to arise from cortical spreading depolarisation and depression in migraine aura. One aim of this review is to make the underlying principles of these models accessible to a general readership. Cortical spreading depolarisation and depression in these models depends on the balance of the diffusion rate between excitation and inhibition and the occurrence of a large spike in activity to initiate spontaneous pattern formation. We review experimental evidence, including recordings of brain activity made during the aura and attack phase, self-reported triggers of migraine, and psychophysical studies of visual processing in migraine with aura, and how these might relate to mechanisms of excitability that make some people susceptible to aura. Increased cortical excitability, increased neural noise, and fluctuations in oscillatory activity across the migraine cycle are all factors that are likely to contribute to the occurrence of migraine aura. There remain many outstanding questions relating to the current limitations of both models and experimental evidence. Nevertheless, reaction–diffusion models, by providing an integrative theoretical framework, support the generation of testable experimental hypotheses to guide future research.

Individuals with migraine show differences in visual perception compared to control groups. It has been suggested that differences in lateral interactions between neurons might account for some of these differences. This study seeks to further establish the strength and spatial extent of excitatory and inhibitory interactions in migraine-with-aura using a classic lateral masking task. Observers indicated which of two intervals contained a centrally presented, vertical Gabor target of varying contrast. In separate blocks of trials, the target was presented alone or was flanked by two additional collinear, high contrast Gabors. Flanker distances varied between 1 and 12 wavelengths of the Gabor stimuli. Overall, contrast thresholds for the migraine group were lower than those in the control group. There was no difference in the degree of lateral interaction in the migraine group. These results are consistent with the previous work showing enhanced contrast sensitivity in migraine-with-aura for small, rapidly presented targets, and they suggest that impaired performance in global perceptual tasks in migraine may be attributed to difficulties in segmenting relevant from irrelevant features, rather than altered local mechanisms.

The binocular energy model of neural responses predicts that depth from binocular disparity might be perceived in the reversed direction when the contrast of dots presented to one eye is reversed. While reversed-depth has been found using anti-correlated random-dot stereograms (ACRDS) the findings are inconsistent across studies. The mixed findings may be accounted for by the presence of a gap between the target and surround, or as a result of overlap of dots around the vertical edges of the stimuli. To test this, we assessed whether (1) the gap size (0, 19.2 or 38.4 arc min) (2) the correlation of dots or (3) the border orientation (circular target, or horizontal or vertical edge) affected the perception of depth. Reversed-depth from ACRDS (circular no-gap condition) was seen by a minority of participants, but this effect reduced as the gap size increased. Depth was mostly perceived in the correct direction for ACRDS edge stimuli, with the effect increasing with the gap size. The inconsistency across conditions can be accounted for by the relative reliability of first- and second-order depth detection mechanisms, and the coarse spatial resolution of the latter.