Transcranial magnetic stimulation (TMS) in controlled treatment studies: are some “sham” forms active?

Background: Carefully designed controlled studies are essential in further evaluating the therapeutic efficacy of transcranial magnetic stimulation (TMS) in psychiatric disorders. A major methodological concern is the design of the “sham” control for TMS. An ideal sham would produce negligible cortical stimulation in conjunction with a scalp sensation akin to real treatment. Strategies employed so far include alterations in the position of the stimulating coil, but there has been little systematic study of their validity. In this study, we investigated the effects of different coil positions on cortical activation and scalp sensation. Methods: In nine normal subjects, single TMS pulses were administered at a range of intensities with a “figure eight” coil held in various positions over the left primary motor cortex. Responses were measured as motor-evoked potentials in the right first dorsal interosseus muscle. Scalp sensation to TMS with the coil in various positions over the prefrontal area was also assessed. Results: None of the coil positions studied met the criteria for an ideal sham. Arrangements associated with a higher likelihood of scalp sensation were also more likely to stimulate the cortex. Conclusions: The choice of a sham for TMS involves a trade-off between effective blinding and truly inactive “stimulation.” Further research is needed to develop the best sham condition for a range of applications.