During a debate session at the 19th Congress of the International Headache Society (IHC), Prof. Gianluca Coppola (Sapienza University of Rome) and Prof. Trond Sand (Norwegian University of Science and Technology) presented evidence supporting their opinions on the question “Is the migraine cortex inherently hyper-responsive?”

Prof. Gianluca Coppola: The migraine cortex is inherently hyper-responsive

Prof. Coppola began his presentation by describing the dual process theory, which includes two distinct and independent processes which govern the behavioral response to repetitive sensory stimulation.1 The first process is sensitization, which occurs at the beginning of a test session and is responsible for the transitory increase in response amplitude.2 The second process is habituation, which occurs throughout a test session and is responsible for a delayed response increment.2

“In the presence of a recurrence of attacks, central sensitization amplifies and persists chronic migraine.”
– Prof. Gianluca Coppola (Sapienza University of Rome)

Prof. Coppola proceeded to highlight evidence supporting the hypothesis that potentiation, rather than habituation, characterizes visual evoked potentials in migraine patients between attacks.3 In one key study designed to evaluate this hypothesis, electroencephalography (EEG) was used to compare the neural response to electrical stimulation of the median nerve in healthy volunteers and patients with migraine during the interictal phase.4 Whereas a habituation of responding was observed in healthy volunteers, a potentiation of visual evoked potentials was observed in patients with migraine with and without aura.

To conclude his presentation, Prof. Coppola stated his opinion that this body of evidence is sufficient to demonstrate that the migraine cortex is inherently hyper-responsive.

Prof. Trond Sand: The migraine brain is not inherently hyper-responsive

Prof. Sand stated that although the results presented by Prof. Coppola are promising, there is a need for demonstrating the reproducibility and reliability of the effects observed during these studies. Specifically, Prof. Sand highlighted the importance of ensuring analysis of data from studies is appropriately blinded.

“It is very important to focus on technical recording standards in neurophysiology.”
– Prof. Trond Sand (Norwegian University of Science and Technology)

According to Prof. Sand, studies that use blinded recording and analysis of data have not found a lack of habituation in migraine patients compared with healthy controls. In one study, visual evoked potentials in 41 interictal migraineurs and 30 controls were compared, with habituation observed in both groups.5 Were the hyper-responsivity hypothesis to be correct, potentiation should have been observed among patients with migraine.

To conclude his presentation, Prof. Sand reaffirmed the importance of blind recording and analysis as a method of controlling for unconscious bias. Furthermore, he highlighted the importance of reducing positive and negative bias in research. In positive bias, unexpected findings are actively discarded as being wrong. In negative bias, unexpected outliers may be removed, increasing the likelihood of achieving a hypothesized result.

Conclusion: An exciting time for migraine research

Following their presentations, both Prof. Coppola and Prof. Sand highlighted that new technologies and methods of data analysis have increased the speed at which migraine is being understood. However, this research needs to be rigorous, with replication of important results.


  1. Groves PM, & Thompson RF. Habituation: a dual-process theory. Psychological Review 1970;77:419–450.
  2. Coppola G, et al. Electrophysiological correlates of episodic migraine chronification: evidence for thalamic involvement. J Headache Pain 2013;14:76.
  3. Schoenen J, et al. Potentiation instead of habituation characterizes visual evoked potentials in migraine patients between attacks. Eur J Neurol 1995;2:115–122.
  4. Porcaro C, et al. Impaired brainstem and thalamic high-frequency oscillatory EEG activity in migraine between attacks. Cephalalgia 2017;37:915–926.
  5. Omland PM, et al. Visual evoked potentials in migraine: Is the “neurophysiological hallmark” concept still valid? Clin Neurophysiol 2016;127:810–816.