From neuroimaging to the bedside: Take the sheets off the thalamus

The common migraine phenotypes, in their episodic forms with and without aura, are disorders that manifest with recurrent transient ictal dysfunctions without interictal sequelae. This helps us to understand, on the one hand, why the nature of migraine continues to be so elusive and why, on the other hand, it is one of the most studied pain syndromes. A complex mixture of genetics and environmental factors interact to determine migraine susceptibility, which may be conceptualized as a milieu of subtle factors that is able to cyclically ignite migraine by affecting the interaction between neuronal and vascular components within the brain. The logical consequence is that these elusive factors, if present, should also be detectable in the pain-free period as underlying dysfunctions. Many methods are available nowadays for assessing neural functions atraumatically in humans, contributing to the great advances made in understanding the pathophysiological facets of migraine. Since the most frequent aura symptoms are visual disturbances and because clinical hypersensitivity to environmental light stimuli, i.e. photophobia, is experienced by patients not just during the attack but even outside, several research groups are particularly focused on the study of the visual system in migraine. Above all, using electrophysiological techniques it was observed that migraineurs show an increase in cortical responsivity to any kind of sensory information, visually comprised, with respect to normal subjects (1). However, several relevant questions about cortical hyperresponsivity have not yet been answered, including: Could hyperresponsivity account for the peculiar migraineur propensity to develop attacks? What are the neuroanatomical correlates of cortical hyperresponsivity? Is there any relationship between interictal visual hyperresponsivity and the visual discomfort reported by patients? Could cortical responsivity differ between migraine with and without aura so that they should be considered as two separate entities? The study by Datta et al. (2) published in the current issue of Cephalalgia tried to answer the last three questions by focusing on the neuroimaging correlate of visual cortical hyperresponsivity. To this purpose, they used multi-modality high-resolution (3 Tesla) functional magnetic resonance imaging (fMRI) to examine the hemodynamic brain response (BOLD) to light stimulation in a large cohort of migraine patients during the pain-free state, as well as in healthy controls. This study is distinct from previous reports on the same topic for three reasons: (I) the authors collected a considerably larger cohort of migraineurs and healthy subjects; (II) they studied patients with (MA) and without aura (MO) separately, not pooled together; (III) they also measured baseline metabolic activity, as reflected by resting cerebral blood perfusion. However, certain limitations of the present study should be acknowledged. Although patients were attack free before and during the scanning session, they were not checked for subsequent attacks that might have happened after the scan. This is a very important point, since from neurophysiological studies it emerges that migraineurs’ brain responses change with the time to the next attack as well as in the pre-ictal period, i.e. within 12–24 hours immediately preceding the attack (1). Another limitation, intrinsic in the methodology, is that even if blood flow is a useful surrogate marker for detecting presynaptic activity within brain areas, it does not allow the determination of whether the underlying physiological event is excitatory or inhibitory, or another energy-consuming process. Therefore, a direct comparison with results provided by electrophysiology is hard to make.