Focal electrical stimulation as a sham control for repetitive transcranial magnetic stimulation: Does it truly mimic the cutaneous sensation and pain of active prefrontal repetitive transcranial magnetic stimulation?
BACKGROUND
Repetitive transcranial magnetic stimulation (rTMS) is a novel, noninvasive method of stimulating selected regions of the brain that has both research applications and potential clinical utility, particularly for depression. To conduct high-quality clinical studies of rTMS, it is necessary to have a convincing placebo (or sham) treatment. Prefrontal rTMS causes cutaneous discomfort and muscle twitching; therefore, an optimal control condition, ie, sham condition, would mimic the cutaneous sensation and muscular discomfort of rTMS without stimulating the brain. Ideally, the quality and intensity of the sham condition would feel identical to the quality and intensity of the rTMS condition, except that the sham would have no effect on cortical activity. We designed and built a focal electrical stimulation system as a sham rTMS condition. Although this electrical sham system is superior to methods used in previous studies, little is known about how the new electrical sham system compares with active rTMS in terms of the level of discomfort and type of sensation it produces.


METHODS
We hypothesized that the electrical sham system may not mirror the experimental condition sufficiently. We studied this hypothesis under single-blind conditions in 15 healthy adults by administering either the real or sham rTMS at high and low intensities while subjects, who were unaware of condition, rated subjective qualities of the stimulation (such as tingling, pinching, and piercing), the scalp location of the perception, and the painfulness of the stimuli.


RESULTS
At low-intensity stimulation, the two techniques (active and sham) differ with respect to the subjective quality of the sensation. The differences between real and sham rTMS were less dramatic at higher intensities. The best sham condition that most closely mimics real prefrontal rTMS requires individual titration of the intensity of electrical stimulation across a broad range. Performing this titration without unblinding patients is likely possible, but technically challenging. We propose a new approach to do this.


CONCLUSIONS
We conclude that it is possible to create a truly indistinguishable sham condition (with appropriate acoustic masking as well), but more work is needed beyond these initial attempts.
Brain Stimulation Laboratory (BSL), Psychiatry Department, Medical University of South Carolina (MUSC), Charleston, SC 29425, USA. arana@musc.edu
Ashley B
AB
Arana
Jeffery J
JJ
Borckardt
Raffaella
R
Ricci
Berry
B
Anderson
Xingbao
X
Li
Katherine J
KJ
Linder
James
J
Long
Harold A
HA
Sackeim
Mark S
MS
George
D000328:Adult; D004558:Electric Stimulation / Q000295:instrumentation / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D010919:Placebos; D017397:Prefrontal Cortex / Q000502:physiology*; D012677:Sensation / Q000502:physiology*; D012867:Skin / Q000294:innervation*; D050781:Transcranial Magnetic Stimulation / Q000295:instrumentation / Q000379:methods; D055815:Young Adult
D010919:Placebos