Assessing Hypersensitivity, Cortical Hyperexcitability, and Habituation in Migraine, according to Age and Disease Severity, using Visual Evoked Potentials during Pattern-Reversal Stimulation

Abstract text (incl. figure legends and references)

Objective: Our goal was to test whether hypersensitivity, cortical hyperexcitability, and hyperresponsivity (lack of habituation) are typical of migraine interictally and whether inconsistencies might be attributed to age or disease severity.

Method: Two experiments were carried out on: (1) 18 young patients (22.8±1.89 years) with low-frequency episodic migraine (3.4±3.35 headache days/month) and 27 matched controls (21.8±2.03 years); and (2) 16 middle-aged patients (41.8±9.21 years) with high-frequency episodic migraine (12.4±4.30 headache days/month) and 29 matched controls (39.2±8.84 years). A neurologist confirmed the diagnoses. We obtained migraine phase (using eDiaries), Sensory Perception Quotient (SPQ) scores, and PR-VEPs (N1, P1). Interictal data was analysed; initial sample: 23(1) and 57(2) patients. The SPQ was used to measure hypersensitivity, Group differences in P1-N1 amplitude denoted cortical hyperexcitability, and habituation was defined as a decrease of P1-N1 amplitude across Blocks/Trials. P1-N1 Peak-to-Peak amplitudes were analysed with linear mixed models considering Block (100 trials/Block) or Trial (all trials) and Group.

Results: Patients reported increased sensitivity to visual stimuli on the SPQ ((1)p=0.010; (2)p=0.017) compared to controls. Regarding P1-N1 data, there was no significant main effect of Group in either (1) or (2), ruling out cortical hyperexcitability. Significant interactions between Block-x-Group ((1)p<0.012;(2)p=0.005) and Trial-x-Group ((1)&(2)p<0.0001) were observed. Post-hoc tests indicated habituation both in patients, regardless of age and headache frequency ((1)&(2)p<0.0001), and controls ((1)p=0.001;(2)p<0.0001). Patients showed a sharper habituation slope than controls ((1)p=0.0001;(2)p<0.0001).

Conclusion: Hypersensitivity to visual stimuli was not related to cortical hyperexcitability or interictal habituation using PR-VEPs; these findings did not vary based on age or disease severity in episodic migraine.