Neurophysiology of rTMS: Important caveats when interpreting the results of therapeutic interventions

Abstract

Transcranial magnetic stimulation (TMS) is a safe and non-invasive method of stimulating neurons in intact humans. TMS uses electromagnetic induction to induce weak electric currents in the brain. There is good evidence that repetitive application of TMS (repetitive TMS, rTMS) can produce after-effects, offering potential for clinical application in variety of neurological and psychiatric diseases. Although the mechanisms of this after-effect are not fully understood, because of its similarity to synaptic plasticity in animals, it is generally assumed that rTMS-induced effects may closely relate to synaptic plasticity, such as long-term potentiation (LTP) or depression (LTD). Therefore, the term LTP- or LTD-like is frequently used to describe the changes observed after rTMS. It has yet, however, to be demonstrated that the site of rTMS-induced changes is the synapse. Furthermore, the response to rTMS is highly variable. A number of factors have been identified that could contribute to this, but none of them accounts for a large proportion of the effect. This unavoidable variability of rTMS hampers attempts to assess treatment effectiveness. One potential approach to dealing with this problem is to find strong predictors of the response to rTMS so that parameters of stimulation could be optimized on an individual basis. Another would be to invent new non-invasive stimulation protocols that have more consistent effects in all individuals. Variability in response to rTMS need not be seen as a weakness of this method but a great opportunity to gain further insight into individual differences in the awake human brain.