## 5 Experiments and Results
### Repeated Response Experiment of Brain Stimulation
#### 5.3.2 Procedure  
In this experiment, we stimulated the primary motor cortex of the brain, specifically, the hand motor area (M1-hand), with the developed robotic system. With the help of the robotic system, we stimulated the same spot repeatedly with a time interval. Here, we used a 10-min interval. Only with navigation, it is very difficult or almost impossible to repeatedly stimulate the same spot with less than a 5-mm error [4]. However, the developed automatic positioning system enabled us to perform this experiment. Here, we used a TMS coil to non-invasively stimulate the brain. It is well known that involuntary movement is induced by the stimulation of the brain's motor area. The motor area consists of many small areas corresponding to different parts of the body. In this experiment, we stimulated the hand motor area because hand movement is easy to observe and it is generally stimulated to find the standard threshold value in clinical use. To quantify the motion, we measured EMG signals from the hand when we stimulated the brain. The TMS equipment (TAMAS, REMED Co., Republic of Korea) used for the experiment had a figure-of-eight coil (wing diameter: 75 mm).  
The test subjects placed their right hands in a comfortable position on a cushion while sitting comfortably in a chair, as shown in Figure 10. In addition, we attached an EMG sensor (Shimmer3 EMG Unit, Shimmer Co., Ireland) to the forearm muscle of the subject with Ag/AgCl surface recording electrodes and detected the MEP to verify the accuracy of the repeated stimulus. MEP is what causes the spinal cord and peripheral muscles to produce neuronal electrical signals by a single pulse stimulation of the brain [19]. Since the position of the motor cortex was slightly different for each subject, the stimulation target position for hand movement and the magnitude of EMG signals should be found and adjusted beforehand. When the optimal site was found through trial and error, the relative posture between the robot and the head was stored. This information was used to stimulate the same place in the next session. A motor threshold is defined as the lowest intensity required to elicit an MEP response of at least 50 \(\upmu\)V amplitude when the TMS is applied to the motor cortex. The motor threshold is the optimal intensity. Therefore, if a different brain area from the target area was stimulated, the MEP response would be smaller.  
We first recorded the location where the MEP amplitude was about 50 \(\upmu\)V while stimulating the subject's brain using the integrated system. This process is represented as TMS-MEP pre in Figure 10. A total of three repetition stimulation sessions were conducted at 10-min intervals per session. Between sessions, the subjects were allowed to leave the chair and take a rest in the room. Subjects were stimulated with the same intensity in all sessions, and the intensity was different for each subject.  
Figure 10: Procedure and setup of repeated response experiments of brain stimulation.  
When the positioning error dropped below 0.9 mm through motion compensation control, we let the stimulation occur. Stimulation was conducted five times per session. The interval in a session was about three seconds. This experiment was a single-blind test. The subjects were unaware of this cycle.