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Referee comments: Referee 1 (Alvaro Pascual-Leone)

Posted by PLOS_ONE_Group on 10 Apr 2008 at 16:15 GMT

Referee 1's review (Alvaro Pascual-Leone):

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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.
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This is an interesting paper. The authors describe a novel method to achieve proper blinding for sham TMS. Given the increased use of TMS in cognitive neuroscience and its potential therapeutic uses, a good sham method is certainly needed and those presently available are not satisfactory. The authors propose a method that appears to fulfill many of the critical needs. They present various lines of evidence and convincing data to support their claim that their method ought to be explored further.

The introduction is long. However, it does provide a nice overview of presently available sham TMS methods and their limitations.

For the Motor Physiology studies we are told that the TMS coil for 'clamped' to assure consistent placement. How was this done?
Regarding the motor physiology, the authors elected to determine motor threshold. This seems unfortunate given the more variable nature of this parameter. It seems that measuring the amplitude or the probability of induction of an MEP at a given device output intensity depending on the coil used would be of greater value.

Regarding the results, it seems that pain was significantly less but loudness significantly higher in the sham coil. Surely this could impact the blinding. This should be discussed in more detail. Pain and loudness was only tested in 3 subjects. Why such a small number? In this case TMS was delivered frontally. Why a different target area? Could that have an impact on the findings?

In the experiments on Perceptual Discriminability the authors elected to target Cz. I think this is unfortunate, since, as they acknowledge, frontal or parieto-temporal areas would be a lot more relevant for cognitive science studies with TMS. More importantly, it is likely that the stimulation over Cz (as compared with those other targets) caused significantly less muscle contraction, facial activation, and ultimately discomfort. The authors mention that they did target F3/4 in 'pilot studies' and found the same findings. I think that adding those data would be of value.

I have also a few more, rather minor comments:

Both references given regarding therapeutic applications of TMS refer to psychiatric applications. Perhaps one of them could be changed for a review of TMS applications in neurology.

The circular coil is said to be used 'less in clinical research'. This is probably correct. However, it is the main coil used in clinical neurophysiology applications, as it offers the opportunity to target both motor cortices at the same time with relatively little worry about specific placement or constant positioning. Perhaps this could be added.

Under 'Subjects' in 'Materials and Methods', the second sentence contains a minor grammatical oversight. It should read '....performing TMS experiments....' (rather than experiment).