Repetitive TMS and synaptic plasticity – what is the link?
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During the last two decades, transcranial magnetic stimulation (TMS) has rapidly become a valuable method to investigate non-invasively the human brain. Depending on the stimulation parameters, TMS is able to excite or inhibit the brain, and offers opportunities to study various aspects of brain functioning. It can be used as a tool to explore the excitability of different regions, but it also offers the possibility to localize brain functions in space and time. Furthermore, repetitive TMS (rTMS) is able to induce changes in brain activity that last after stimulation. Therefore, rTMS has therapeutic potential in patients with neurological and psychiatric disorders like stroke, major depression disorder and schizophrenia. The question is, however, by which mechanisms rTMS influences the brain, resulting in these lasting effects. An appealing hypothesis is that the effects of rTMS on the brain are LTD- or LTP-like, as the lasting effects seem to implicate changes in synaptic plasticity. However, is this assumption supported by experiments and is it possible to be more specific about the way rTMS affects the brain? That is the topic of discussion in this thesis. In the first part, we will discuss several forms of synaptic plasticity and the mechanisms underlying these processes. Secondly, different rTMS protocols will be described. In part III, we present several lines of evidence that suggest a link between the effects of rTMS on the one hand and the processes involved in synaptic plasticity on the other. We then discuss these results (part IV), and state that, although these results are important and to a certain extent give insight into the mechanism by which rTMS modifies the brain, they do not provide direct evidence for the hypothesis that rTMS alters synaptic plasticity. In addition, focusing on the synaptic level seems to be too narrow because rTMS-effects can be widespread through the brain. In part V, we look forward to the future of rTMS. We strongly emphasize the need for innovating research in order to investigate the long-lasting effects of rTMS on the human brain into more detail and give suggestions for such experiments. In addition, we point out the importance of such research for the improvement of rTMS as a treatment for neurological and psychiatric disorders. To conclude, we state there are strong indications for a link between rTMS and synaptic plasticity. However, the details of this link need to be further investigated. Future research needs to examine both the local effects of rTMS on the synapse and the effects of rTMS on other, more global levels of brain organization. Only in that way can the after-effects of rTMS on the brain be completely understood.