Subclinical cerebellar dysfunction in patients with migraine: Evidence from eyeblink conditioning

Background: Clinical findings suggest cerebellar dysfunction in patients with migraine. Eyeblink classical conditioning (EBCC) is a simple form of associative learning which depends on the integrity of the cerebellum. The aim of this study was to assess whether EBCC is disturbed in patients with migraine. Methods: A delay conditioning paradigm was used in the headache-free interval in 32 female patients with migraine, in 24 of them without (MwoA) and eight with aura (MwA), and in 32 age-matched female controls. As primary outcome measure acquisition and as secondary outcome measures timing and extinction of conditioned eyeblink responses (CR) were assessed. Results: CR acquisition was significantly reduced in all migraine patients (mean total CR incidence 35.2 +/- 22.1%) compared to controls (54.7 +/- 21.3%; p < 0.001; Bonferroni-corrected p level < 0.025) and in MwA patients (19.9 +/- 20.2%) compared to matched controls (58.2 +/- 27.0%; p = 0.006) but not in MwoA patients (40.3 +/- 20.6%) compared to matched controls (53.6 +/- 19.7%; p = 0.028; Bonferroni-corrected p level < 0.0166). Decrease of CR incidences in MwA patients was not significantly different compared to MwoA patients (p = 0.021; Bonferroni-corrected p level < 0.0166). CR timing and extinction was not affected in migraine patients. Conclusions: Reduced acquisition of CRs in the cohort of female patients studied here supports findings of a cerebellar dysfunction in migraine.