15 healthy adults (9 men) ages 21–48 were stimulated with both real rTMS and the electrical sham control condition. Each subject was screened for a personal or family history of epilepsy 11
and signed written informed consent approved by the MUSC IRB. We used a Neuronetics system and Mecta Spectrum 5000Q (sham). To deliver the sham stimulation, one researcher triggered the electrical stimulation with a Neotonus sham coil attached, while the other researcher adjusted the appropriate settings with the RCS MECTA program. This modified ECT device is a constant current device and uses internal tests to assure that only a minimal intensity (20mA) of stimulation will be delivered to the subject, to prevent risk of seizures in the participants. The Spectrum 5000Q ECT machine delivered the electrical stimulation to the electrodes, while the Neotonus sham coil mimicked the noise and placement of the real rTMS coil and triggered the timing of the Spectrum machine. Both the real rTMS coil and the sham ran for 4 seconds at 10 Hz. Each subject received a total of 8 real TMSstimulations and 16 sham stimulations.
The subjects reclined in a supine position in the Neuronetics chair (). The forehead was swabbed with alcohol, and Pre Tac conductive skin preparation gel was placed in the general areas of electrode placement (medial and lateral). The medial electrode was centered at the nose and placed about 1cm above the eyebrows, and then the lateral electrode was placed about 1 cm to the left of the medial electrode and 1 cm above the eyebrow. The cords were placed posterior to avoid tugging and to keep the subject blinded about the anode/cathode placement. Before beginning electrical stimulation, the system was tested for static impedance with a target of less than 1000 ohms.
Experimental Set-up. Electrodes are placed on forehead for sham stimulation, and the TMS coil is positioned over the left-prefrontal cortex.
For electrical stimulation, we used one dose at 5mA for all subjects and then we also delivered an intensity that was about 70% (7±1/10) of the subject’s maximum pain tolerance, which we refer to in this study as ‘high intensity’ sham. This high intensity sham was found for each individual through an ascending staircase method where we started the machine at 5 mA and asked the subject to rate the pain on a scale of 0 to 10, with 0 being “no pain at all” and 10 being “the worst pain imaginable.” If the subject rated the delivered intensity below 7, the intensity was increased. If the subject rated the delivered intensity above 7, the intensity was decreased. Given the limits of this methodology, our target pain ratings were 7 ± 1. If inconsistent or unusual ratings were given, the stimulations were repeated.
The method routinely used to identify the correct area for rTMS treatment uses the motor cortex as an anatomical marker to locate the left prefrontal cortex 12
. The resting motor threshold is found by exploring for the scalp location over the motor cortex area that controls right-handed muscle movement. The location is identified using .3 Hz at low intensity TMS and is verified when the TMS pulse produces movement in the right hand. Next, to find the lowest intensity required to cause a muscle twitch or movement, a computerized algorithmic system, Adaptive P.E.S.T. 3 program was used with visible movement 13
. Once the motor threshold was determined, the experiment began.
The stimulations were run in a block, randomized fashion where the subject would first either receive 8 rTMS stimulations or 16 sham stimulations. All of the conditions within each of the two blocks were randomized. For rTMS, only two intensities were delivered (110% and 120% of the individual’s motor threshold). For the sham condition, each stimulation was randomized by intensity (5mA, 70% tolerance), medial placement of electrode (anode, cathode), and type of current (unidirectional, bidirectional). The combination of the three conditions was changed every two trains, giving a total of 8 combinations of stimulation, each given twice. The entire session took approximately one hour.
For each stimulation, the subject rated the sensation using a custom-developed “Face Locator” software program. This software program allows subjects to draw on a digital image of a human face where the sensation was felt. The subjects can vary the pen width to easily draw larger or smaller areas. The program records the left, right, top, and bottom boundaries of the indicated area of sensation as well as the center of the sensation on both the x and y axes. The Face Locator Program was projected on the ceiling over the Neuronetics chair, allowing the supine positioned subject to see it clearly without having to move his or her head. The subject responded to each stimulation using a mouse with the right hand. The subject drew the position and area of the sensation, and then using a visual analog scale (VAS) the subject rated the subjective qualities of the sensation (pain, tingling, sharpness, piercing, electric, tugging, pinching, and intolerability). Finally, the subject had the option of indicating whether or not the sensation had any directional quality by moving a digital compass if the sensation moved in a direction away from its origin.
VAS data was exported into a SPSS datafile for statistical analysis. Multivariate Analysis of Variance (MANOVA) was used to evaluate the differences between real and sham TMS across all sensation ratings collected. In order to analyze data on the position and area of the sensations, a program was written to open each subject’s individual Face Locator pictures and calculate the mean number of blue (i.e., activated) pixels within each 25×25 pixel block across the entire picture. It then generates a new picture that represents average activation in 25×25 pixel blocks and represents it with different shades of green (bright green means there were many combined blue pixels within a 25×25 pixel block and dark means there were few blue pixels in a block).