Fumiko Hoeft, Daw-An Wu, Arvel Hernandez, Gary H. Glover, Shinsuke Shimojo

Transcranial magnetic stimulation (TMS) is increasingly being used to demonstrate the causal links between brain and behavior in humans. Further, extensive clinical trials are being conducted to investigate the therapeutic role of TMS in disorders such as depression. Because TMS causes strong peripheral effects such as auditory clicks and muscle twitches, experimental artifacts such as subject bias and placebo effect are clear concerns. Several sham TMS methods have been developed, but none of the techniques allows one to intermix real and sham TMS on a trial-by-trial basis in a double-blind manner. We have developed an attachment that allows fast, automated switching between Standard TMS and two types of control TMS (Sham and Reverse) without movement of the coil or reconfiguration of the setup. We validate the setup by performing mathematical modeling, search-coil and physiological measurements. To see if the stimulus conditions can be blinded, we conduct perceptual discrimination and sensory perception studies. We verify that the physical properties of the stimulus are appropriate, and that successive stimuli do not contaminate each other. We find that the threshold for motor activation is significantly higher for Reversed than for Standard stimulation, and that Sham stimulation entirely fails to activate muscle potentials. Subjects and experimenters perform poorly at discriminating between Sham and Standard TMS with a figure-of-eight coil, and between Reverse and Standard TMS with a circular coil. Our results raise the possibility of utilizing this technique for a wide range of applications.