Effects of repetitive transcranial magnetic stimulation on visual evoked potentials: new insights in healthy subjects

In a previous comparative study with migraineurs, we found in 24 normal subjects that the amplitude of the pattern-reversal visual evoked potential (PR-VEP) in the first block of 100 responses and its habituation over 6 sequential blocks were significantly decreased after 1 Hz repetitive transcranial magnetic stimulation (rTMS), while 10 Hz rTMS had no significant effect. We report here our results on the reproducibility of the rTMS effect studied in ten of these subjects by repeating the recordings for each frequency three times on different days. We have also reanalysed the data obtained in 24 normal subjects, looking separately at the results in those stimulated at an intensity equal to phosphene threshold (group 1; n=14) and those stimulated at 110% of motor threshold because of unelicitable phosphenes (group 2; n=10). We finally determined the precise duration of the rTMS effect. Despite some interindividual variability, the effects of both rTMS frequencies on first block amplitude, habituation between first and sixth block and habituation slope over the six blocks were highly reproducible. The only difference between the two groups of subjects was the effect of 1 Hz rTMS on the second measured PR-VEP component. Whereas first block amplitude of the first P1-N1 component and habituation were decreased in both groups, such a decrease was found for the second P1-N2 component only in group 1 stimulated at phosphene threshold. The dishabituation of the N1-P1 component after 1 Hz rTMS was maximal at 15 min, but lasted up to 33 min, while that of P1-N2 disappeared after 3 min. There was a non-significant trend ( p=0.06) for a reduction of first block amplitude after 10 Hz rTMS in the total group of subjects, but no effect on habituation. The inhibitory effect of 1 Hz rTMS, which reduces in healthy controls both first block PR-VEP amplitude and habituation, probably by decreasing the preactivation excitability level of the underlying visual cortex, is thus reproducible and long lasting. Long trains of 10 Hz rTMS tend to attenuate reproducibly the cortical preactivation level in normal subjects, but they do not affect habituation at all, which contrasts with their effect in migraineurs, in whom, as previously reported, they significantly correct the habituation deficit. The absence of an effect of 1 Hz rTMS on PR-VEP P1-N2 in subjects stimulated at 110% of motor threshold may be explained by the deeper anatomical location of the cortical generators of this component and the lower stimulation intensity used. Taken together our results confirm that the effect of rTMS on the underlying cortex depends on several variables such as frequency, intensity and level of cortical preactivation.