Transcranial Magnetic Stimulation

Transcranial Magnetic Stimulation (TMS) is a new non-invasive method that enables the delivery of an electric stimulation to the cortex. With this technique, a cortical excitation is created using magnetic impulses emitted by an external stimulation coil. A suite of such stimulations is able to modulate either up or down the cortical excitability for hours or even weeks, depending on stimulation parameters. As such, it provides a potential non-invasive therapy for many functional brain disorders. Its efficiency has currently strong support in the case of refractory depression and hallucinations with mean effect size of 0.8 (~ number needed to treat between 3 and 5), and studies are currently being conducted for other psychiatric pathologies like post-traumatic stress disorder, compulsive obsessive disorders, negative symptoms of schizophrenia and neurological diseases like partial epilepsy of the motor cortex, pain, dystonia, Parkinson’s disease and even tinnitus.

However, even if the applicability of this technique seems very promising, it is not yet widely accepted because of the observed variability of efficiency between patients. This is partly due to the problem of defining right stimulation parameters (frequency, organisation, intensity etc…). But it is more related to the definition of the target area and the control of coil positioning.

Target definition

The knowledge concerning the regions to be stimulated is still in infancy for many diseases. Epilepsy is one exception with a long history of localisation strategy of the ''epileptic zone'' required for surgical interventions. But the strategy can potentially be generalized to other symptoms like auditory hallucinations: fMRI allows mapping of the regions more active during the symptom for each patient. Such adaptation is probably required because there are major variations between patients.

Coil positioning

The correct positioning of the coil in front of the target regions is performed by neuro-navigation using frameless stereotaxy. This system uses pre-operative MRI images with superimposed fMRI results, fiducials on the patient head and on the coil, and infrared stereo cameras. The placement of the coil on the head of the patient is performed manually by looking at a screen where the coil position and orientation are indicated in real-time with respect to the target region.

By now, the majority of teams position the coil on one target point, without taking into account the whole target regions. This one is sometimes as long as 5 to 6 cm, i.e. the superior longitudinal sulcus in the case of hallucinations (Figure 1), without clear “hot-spot” that should be more stimulated than another. The displacement of the coil in a regular movement along such target (Figure 2) with adaptation to the patient movements is difficult and physically too demanding to be performed manually.

Fig. 1. The STS more activated in a case of verbal hallucinations         Fig. 2. Example of the stimulated trajectory

A robotic system is therefore needed to perform more easily, reliably and efficiently rTMS procedure for therapeutic purpose. To our knowledge, little work exists on robotised transcranial magnetic stimulation. Therefore, we developed a novel robotic system allowing a reliable clinical evaluation of the TMS procedure.

The medical constraints

The robotic device aims at replacing the physician during the stimulation session. The system will work in a fully automatic mode, taking into account safety and medical constraints.

The physician’s task consists in positioning the magnetic figure-of-eight stimulation coil in close contact with the patient’s head with a precision of 1 to 5 mm. The patient security implies the definition of a maximum threshold for the force applied to the skull. In addition, the system has to be able to detect and adapt to small head movements. As the electrical field induced in the brain is maximal along the line that is orthogonal to the coil centre, the coil plane needs to be tangent to the head. The orientation of the coil has to be precisely controlled since the response to the stimulation also depends on it.

The robotic system and associated workflow

The proposed robotic system is based on the analysis of the previously described medical

constraints:

The workflow of a robotised TMS procedure is conceptually the same as for manual procedures. However, some additional tasks are mandatory to allow an autonomous stimulation session:

• Firstly, different MRI and fMRI images are recorded which are used to build a 3D model of the brain and the head of the patient.
• Secondly, in a pre-interventional planning session, the neurologist specifies the cortical regions to be stimulated and their orders based on the fMRI data. For each of them, he defines the stimulation parameters such frequency and intensity.
• Thirdly, the neuro-navigation system computes the trajectory of the coil center on the head that best stimulates each area allowing for the required specifications.
• Fourthly, the patient is placed under the robotic system and a registration of his head with the robot and the 3D model is carried out.
• Finally, the stimulation procedure is executed autonomously enabling the head movements of the patient.

The physician may repeat exactly the same automatic stimulation procedure as many times as prescribed by the treatment, and could retrospectively control the quality of the procedure based on the registration of the coil position for each stimulation.

Perspectives

In the future, we plan to use the robotic rTMS system to clinically validate its therapeutic effects on verbal hallucinations, depression and partial epilepsy of non-removable cortices. Even in cases of non-complex target zone, the procedure is expected to be more accurate, efficient and easy to perform and less time-consuming. It should allow the diffusion of rTMS with a good economical profile, as one technician could supervise more than one rTMS-robotic device, allowing the physician to limit his intervention to the planning and side effect management.