Lau, Chi Ieong; (2024) Exploring the mechanisms of chronic migraine: insights from behaviour, physiology and advanced neuroimaging. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Chronic migraine (CM) often co-occurs with a debilitating condition known as medication overuse headache (MOH), where headaches paradoxically worsen due to medication overuse. The reasons some CM patients are prone to MOH remain unclear, but psychological factors such as pain perception or medication decision- making may play a role. This thesis explores these aspects through behavioural, neuroimaging, and physiological experiments. The first study compared decision-making in CM patients with MOH, CM patients without MOH, and healthy controls. CM patients with MOH showed impaired decision-making under ambiguity but not under risk. Their performance inversely correlated with analgesic consumption, suggesting a link between decision-making under ambiguity and MOH. The second study investigated the neural mechanisms underlying these findings. CM patients with MOH had reduced cortical thickness and subcortical nuclei volume in key components of the mesocorticolimbic reward circuity compared to those without MOH. Anterior cingulate cortical thickness inversely correlated with substance dependence scale, supporting the hypothesis that medication overuse in CM patients is related to a dysregulated reward system. Subsequently, I explored the potential to modulate cortical excitability in the visual cortex using transcranial direct current stimulation (tDCS). My third study showed a deficient habituation of pattern-reversal visual evoked potential (VEP) response in migraine patients compared to healthy controls. However, the final study found no significant tDCS effects on VEP amplitudes or habituation slopes in heathy subjects, questioning assumptions about polarity-specific tDCS effects in the visual cortex and suggesting that common tDCS protocols for the motor cortex may not be effective for the visual cortex. Collectively, these findings provide novel evidence that CM with MOH is linked to a dysregulated reward system. The lack of durable tDCS effects in the visual cortex indicates a different susceptibility to tDCS compared to the motor cortex. Future studies with alternative methods are warranted to explore potential therapeutic effects of tDCS for migraine.

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