The effect of 1 Hz rTMS over the primary visual cortex was evaluated by using the simultaneous TMS-fMRI combination. Brain functional response induced by TMS stimulus over the occipital area and associated with phosphene perception was obtained before and after an rTMS session and compared. The results revealed a different pattern of brain activation before and after 1 Hz rTMS for the group able to see phosphene; however, for those who lack this perception, significant increase/decrease in brain activation occurred in few brain areas, after the rTMS train, showing an overall no significant change in brain activation.
Results from our previous work showed a connection between the stimulus site (left cuneus) and the left parietal lobe and left frontal-eye-fields for those who see phosphene [14
]; thus, the observed increase in the PT, induced by 1 Hz rTMS, that indicates an inhibitory effect on the cortical area, would suggest that there was a decrease in brain activation in these areas after the rTMS session. However, the comparison of the statistical maps before and after the rTMS run shows decrease in brain activation after rTMS at the right cuneus, right parietal, and left FEF instead. Reduction in brain activation was also observed in the medial frontal gyrus (motor area) and right brainstem (midbrain), a part of the brainstem that has a conduit function for eyes input (superior colliculus) [23
] and motor coordination (the red nucleus) [24
]; therefore decrease in brain activation in these areas is explained by the reduced phosphene sensation induced by 1 Hz, that led to reduced button press frequency. Finally, the overall change in the brain activation pattern in this group indicates that low frequency rTMS has a significant effect in their brains, but it cannot be considered completely inhibitory.
The group unable to see phosphene showed a significant reduction of brain activation after 1 Hz rTMS just in one brain area, the lingual gyrus at the occipital lobe, and increase in brain activation just in two brain regions, the precentral gyrus at the frontal lobe, and precuneus at the parietal lobe. This points to an inhibitory effect near the stimulation site (left cuneus), but opposite effect on the parietal and frontal lobe, suggesting that low frequency rTMS cannot be considered inhibitory for this group. In fact, their lack of phosphene sensation and the non-significant changes in brain activation after the rTMS session indicate that TMS does not have a major effect on brain function in this group. Accordingly, rTMS might not be a good treatment procedure for this population.
In this study, we also evaluated whether any unwanted persistent effects on behavior/cognition might be induced during the TMS sessions, for safety purpose only, since it is recommended at the guidelines for rTMS use [15
]. The results from the neuropsychological tests demonstrated, as expected, that there were no detrimental effects on behavior/cognition induced by either the low frequency rTMS session or the two simultaneous TMS-fMRI sessions, suggesting that this type of study can be safely used in healthy adult volunteers.
Low frequency rTMS (1 Hz) has shown to increases motor [7
] and phoshene [4
] thresholds when applied for 15 minutes in a group of healthy individuals over the motor or occipital cortices, respectively; therefore suggesting an inhibitory effect in these areas. Based on these findings, low frequency rTMS has been applied in other brain regions to induce inhibition of those brain areas. However, our results, employing imaging to monitor the effect of 1 Hz rTMS in the brain of healthy individuals, show that, although an increase in PT suggests its inhibitory effect at the stimulus site, such an effect may not be true for other brain regions.
Moreover, for those people unable to see phosphene reduction in cortical excitability cannot be verified, since PT cannot be measured and change in brain activation occurred just in few brain regions. Of course, our results are based on a small number of volunteers and future studies, with a larger number of participants, are needed to replicate and validate these preliminary results. In particular, changes in the lateralization in the insula and cerebellum activations, as a result of rTMS, need to be clarified. Nevertheless, this work demonstrated the value of using simultaneous TMS-fMRI or even the combination of TMS and other imaging modalities to better understand the nature of the effect of rTMS in the brain.