Light, photophobia and headache: an investigation of visually-induced migraine

Thesis

Exacerbation of headache by light is a major symptom in migraine. A recent study unraveled the non-image forming (NIF) visual pathway to be a key component underlying photophobia in migraine. Several lines of evidence also indicate that an altered cortical excitability may render migraineurs more susceptible to attacks, although it is unclear whether the cortex is more or less excitable. Accordingly, this thesis investigated the link between migraine, visual systems and brain responsiveness using three complementary approaches. To begin with, I assessed the response of the NIF visual system to light of different wavelengths in healthy subjects. My results provided the first neuroimaging evidence that the suprachiasmatic nucleus (SCN) of the NIF system displays a sustained response to blue light but not to other wavelengths. This highlights the unique property of the SCN for mediating the circadian cycle, which some investigators have suggested drive the periodicity of migraine attacks.

Next, I examined the interictal cortical sensitivity to light and visual stimuli in migraine. The fMRI results revealed a hypo-excitable response to diffuse illumination in migraineurs compared to healthy controls. The response, however, did not differ when subjects were exposed to a more aversive flickering checkerboard stimulus. Furthermore, the phenomenon appeared to be magnified in a group harboring the TRESK variant, who may be considered an extreme form of the migraine spectrum. This suggests that the initial cortical hypo- excitability may serve as a protective mechanism against further attacks. Surprisingly, I found no disturbance of glutamate, GABA and NAA in the visual cortex of interictal migraine subjects, arguing against the notion that these metabolites may mediate the protective mechanism or predispose the brain to migraine attacks. Finally, I optimized the PCR and prepared a DNA pool of 741 migraineurs and 416 controls for sequencing four candidate genes including TRESK and OPN4. Variants identified in these genes that associate with migraine may provide mechanistic insights into how genetic backgrounds alters neuronal and brain responsiveness and how this in turn increases migraine liability.

Taken together, my studies reveal cortical hypo-excitability in patients with migraine between attacks and established a foundation for future studies including the NIF visual system in migraine. Longitudinal studies will also help unravel compensatory from primary changes in the migraine brain.

Authors: Lau, C

• Publication date: 2012
• Type of award: MSc by Research
• Level of award: Masters
• Awarding institution: University of Oxford
• Language: English
• Keywords: trigger; DNA sequencing; magnetic resonance spectroscopy; suprachiasmatic nucleus; DNA pooling; photophobia; genetics; visual system; headache; light; visual cortex; magnetic resonance imaging; polymerase chain reaction; circadian cycle; cortical excitability; migraine
• Subjects: Neuroscience; Cognitive Neuroscience; Neuropsychology; Cognition; Neurology; Psychological medicine; Ophthamology; Genetics (life sciences); Medical Sciences; Genetics (medical sciences); Perception; Life Sciences