Effects of repetitive transcranial magnetic stimulation on visual evoked potentials in migraine

Abstract

Between attacks, migraine patients are characterized by potentiation instead of habituation of stimulation-evoked cortical responses. It is debated whether this is due to increased or decreased cortical excitability. We have studied the changes in visual cortex excitability by recording pattern-reversal visual evoked potentials (PR-VEP) after low- and high-frequency repetitive transcranial magnetic stimulation (rTMS), known respectively for their inhibitory and excitatory effect on the cortex. In 30 patients (20 migraine without, 10 with aura) and 24 healthy volunteers, rTMS of the occipital cortex was performed with a focal figure-of-eight magnetic coil (Magstim). Nine hundred pulses were delivered randomly at 1 or 10 Hz in two separate sessions. Stimulus intensity was set to the phosphene threshold or to 110% of the motor threshold if no phosphenes were elicited. Before and after rTMS, PR-VEP were averaged sequentially in six blocks of 100zztieresponses during uninterrupted 3.1 Hz stimulation. In healthy volunteers, PR-VEP amplitude was significantly decreased in the first block after 1 Hz rTMS and the habituation normally found in successive blocks after sustained stimulation was significantly attenuated. In migraine patients, 10 Hz rTMS was followed by a significant increase of first block PR-VEP amplitude and by a reversal to normal habituation of the potentiation (or dishabituation) characteristic of the disorder. This effect was similar in both forms of migraine and lasted for at least 9 min. There were no significant changes of PR-VEP amplitudes after 1 Hz rTMS in migraineurs and after 10 Hz rTMS in healthy volunteers, nor after sham stimulation. The recovery of a normal PR-VEP habituation pattern after high-frequency rTMS is probably due to activation of the visual cortex and the dishabituation in healthy volunteers to cortical inhibition. We conclude, therefore, that the deficient interictal PR-VEP habituation in migraine is due to a reduced, and not to an increased, pre-activation excitability level of the visual cortex.

Visual evoked potentials in migraine: Is the “neurophysiological hallmark” concept still valid?

“…Disease duration (headache-history), migraine-frequency and usual headache duration were similar in the present study and in several studies that reported lack of habituation in migraine (Afra et al, 2000b;Bohotin et al, 2002;Coppola et al, 2010b;Coppola et al, 2010a;Ozkul and Bozlar, 2002). It is therefore unlikely that the migraineurs in those studies had a more severe disorder and therefore more pronounced VEP alterations.…”

“…Several studies merely investigated how lack of VEP habituation in migraineurs is affected by interventions, such as coloured glass (Afra et al, 2000a), fluoxetine (Ozkul and Bozlar, 2002), repetitive transcranial magnetic stimulation (Bohotin et al, 2002;Fumal et al, 2006), cold pressor test (Coppola et al, 2010a), hyperventilation (Coppola et al, 2010b), light deprivation (Coppola et al, 2011) and direct current stimulation . Other studies investigated how lack of VEP habituation relates to other measures, such as personality tests (Wang et al, 1999), cortical auditory evoked potentials (Afra et al, 2000b) and nociceptive blink reflex (Di Clemente et al, 2005).…”

“…Cross-sectional migraine studies often include migraineurs that have on average 2-3 attacks per month, and define the interictal period as > 2 or > 3 days before and after the nearest migraine attack (Coppola et al, 2010a;Di Clemente et al, 2005). Yet, most studies have not reported exclusions of preictal, ictal or postictal recordings, or how these recordings were handled (Afra et al, 1998;Afra et al, 2000b;Bohotin et al, 2002;Coppola et al, 2007b;Coppola et al, 2011;Coppola et al, 2010b;Coppola et al, 2010a;Coppola et al, 2013b;Di Clemente et al, 2005;Fumal et al, 2006;Ozkul and Bozlar, 2002;Schoenen et al, 1995;Vigano et al, 2013). Systematic exclusion of subjects may influence study results and it is therefore unfortunate that most studies do not disclose sufficient details regarding exclusions.…”

“…Some studies had considerable differences in age and gender distribution between migraine and control groups (e.g. Afra et al, 1998;Bohotin et al, 2002;Di Clemente et al, 2005). In studies that reported lack of habituation the migraineurs were outpatients from specialized headache clinics while the controls were hospital employees, laboratory staff, medical students and/or health care professionals (Afra et al, 1998;Afra et al, 2000b;Bednar et al, 2014;Bohotin et al, 2002;Coppola et al, 2011;Coppola et al, 2013b;Ozkul and Bozlar, 2002;Schoenen et al, 1995;Wang et al, 1999).…”

“…Most studies that reported lack of habituation in migraineurs were by one internationally collaborating group of authors (Afra et al, 1998;Afra et al, 2000b;Bohotin et al, 2002;Coppola et al, 2007b;Coppola et al, 2011;Coppola et al, 2010b;Coppola et al, 2010a;Coppola et al, 2013b;Di Clemente et al, 2005;Fumal et al, 2006;Schoenen et al, 1995;Vigano et al, 2013). As far as we know, lack of VEP habituation been independently confirmed in two studies (Bednar et al, 2014;Ozkul and Bozlar, 2002), while two other groups have not managed to reproduce this finding (Oelkers-Ax et al, 2005;Oelkers et al, 1999;Omland et al, 2013;Sand et al, 2008).…”