Abstract
For many decades, clinicians and scientists have been particularly interested in those aspects of migraine that relate to the various components of the visual system. This is less surprising than it may seem, since many patients report prominent and at times incapacitating visual features. Among the most enigmatic of these one may list the scintillations and fortification spectra of the characteristic visual aura, which gave impetus to research on the phenomenon of cortical spreading depression of Leao and continues to fascinate physicians and researchers alike. Another distinguishable visual feature of migraine is the intolerance to light both during and between attacks. Photophobia is a prominent complaint in over 85% of migraineurs and constitutes one of the International Headache Society diagnostic features. Intolerance to several aspects of our visual environment (glare, flicker, patterns, etc.) between attacks is reported in up to 90% of migraineurs in one large series (1), and may be reported both as discomfort and intolerance to light and/or patterns or the occurrence of visuoperceptual distortions, but may also contribute to the generation of a migraine attack, notably with patterned visual stimuli (2).
Several subtle indications of visual system dysfunction may be perceived only during well-controlled psychophysical and neurophysiological experimental settings. While some of these are thought to represent dysfunctions of visual processing at the precortical level in the parvocellular part of the lateral geniculate nucleus (3), the majority of reports, however, point to a failure of cortical processing. Several components of visual processing assessed psychophysically [e.g. target detection (4), orientation discrimination (5)], visual contrast gain control (6)) as well as neurophysiologically [habituation (7), transcranial magnetic stimulation (TMS) (8), magnetic suppression of perceptual accuracy (MSPA) (9)] have all been shown to be abnormal in interictal migraineurs, and some of these were correlated with the duration of the disorder.
Comparatively little research attention has been directed towards colour processing in migraineurs. Wilkins et al. have studied the effects of tinted lenses on the incidence of headache and found that subjects wearing those coloured lenses that optimally reduced visual distortion had a non-significant reduction of their headache frequency compared with subjects wearing control lenses (10). Afra et al. found no effect of coloured lenses on habituation patterns in migraineurs, thus, in their opinion, confirming hypoexcitability (11). McKendrick et al. reported sensitivity deficits in a considerable proportion of migraineurs applying short-wavelength automated perimetry (12).
The discrimination of colour is a complex process involving retinal, subcortical and cortical components. The identification of colour does not simply rely on the detection of the wavelength composition of the light reflected from an object's surface, but rather involves an active analysis and comparison of the light reflected from an object in relation to its background. The paper by Shepherd published in this issue of Cephalalgia focuses on the psychophysical properties of those constituents of the visual system that are involved in the first stage of colour vision, i.e. the colour-sensitive photoceptors in the retina (cones) and their connections to the lateral geniculate nucleus and primary visual cortex (13). Individual cones contain one of three visual pigments which contribute to the differential response of each cone to the spectral composition of reflected light. S-cones are preferentially activated by short wavelength (blue), M-cones are most sensitive to medium wavelengths (green) and long wavelengths (red) make a strong contribution to the activation of L-cones. Under experimental conditions where background colour and luminance are controlled for and colour opponency (i.e. the phenomenon that certain colour pairs are cancelled out) is avoided, the perception of colour is dependent on the relative contribution of the signals in the parallel S-, M- and L-systems. Because the wavelength spectra of M- and L-cones show a considerable overlap but are separated from the S-cone spectrum, two cardinal colour directions may be identified; in one direction there is signal variation in the S-system and a constant signal in the L- and M-systems, whereas in the other direction only the ratio of L- to M-signal varies. It is this principle of selective cone activation along the cardinal colour directions that is at the basis of the experiments in the paper by Shepherd.
Using three different experimental designs it is shown that colour sensitivity is different in migraineurs compared with an age-matched control group. Notably, these differences are restricted to colours detected by S-cones. Migraineurs made more errors in a detection threshold experiment. When requested to adjust the colour of objects uniformly around a standard colour, migraineurs set less saturated colours. Moreover, there was a positive correlation between the performance in both experiments, supporting the robustness of the observations.
Rather than carrying clinical significance (migraineurs do not complain of problems in colour perception), this dysfunction of the S-cone pathways is particularly interesting from a pathophysiological perspective. Does this impairment of visual physiology inform us about a possible site relevant to the pathobiology of migraine, and how do these observations compare with our current knowledge of visual system dysfunction in migraine? Current knowledge of the physiology of the perception of colour indicates that the spectral information of visual stimuli is neurally encoded in the trichromatic S-L-M-system and relayed to the visual cortex in two chromatic opponent systems which are separated up to the visual cortex. As such, although Shepherd's findings unambiguously support the notion of a dysfunctional visual system in migraineurs, they do not yet provide additional arguments to pinpoint this dysfunction to any particular part of the visual system beyond the retina.