MRI-Guided Repetitive Transcranial Magnetic Stimulation to the Dorsomedial Prefrontal Cortex

Abstract

Source: Dunlop, K., et al. MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder. J. Vis. Exp. (2015)

This video demonstrates the procedure for MRI-guided repetitive transcranial magnetic stimulation (rTMS) targeting the dorsomedial prefrontal cortex (dmPFC) to treat depression.

Protocol

All procedures involving human participants have been performed in compliance with the institutional, national, and international guidelines for human welfare and have been reviewed by the local institutional review board.

1. Repetitive transcranial magnetic stimulation (rTMS) treatment & adaptive titration

1. Perform a course of neuronavigated dorsomedial prefrontal cortex (dmPFC) -rTMS, using a total of 20-30 daily sessions over 4-6 weeks. For treatments, use the 120° angled, fluid-cooled coil and the parameters listed below for dmPFC stimulation in each treatment session (refer to Table of Materials).
2. Seat the patient in the treatment chair, adjusting the camera for an unobstructed view of the patient.
3. Place a headband with a marker clip attached to it around the patient’s head (placed laterally so as not to block the rTMS coil placement over the medial target site) as described above. Using a camera, the neuronavigation system, will detect the marker clip and will allow for preprocessing and neuronavigation.
4. Load the preprocessed anatomical scans to the neuronavigation program and turn on the camera.
5. Using a neuronavigation pen, highlight each scalp target point on the patient. The movements made with the neuronavigation pen will be projected on the television screen in the form of red lines.
6. Place the coil over the dmPFC target under magnetic resonance imaging (MRI) guidance using the neuronavigation system. For verification purposes, this point should lie close to 25% of the distance from nasion to inion. Orient the coil laterally, with the handle pointing away from the hemisphere to be stimulated. Stimulate the left hemisphere, then reorient the coil by 180° to stimulate the right hemisphere, maintaining the vertex in the same location over the dmPFC scalp site.
7. Ensure that the scalp site for dmPFC remains in close contact with the coil itself throughout treatment. Ensure that the patient and operator wear earplugs or other hearing protection during treatment.
8. For 10 Hz stimulation, use a duty cycle of 5 sec on, 10 seconds off for a total of 60 trains (3,000 pulses) per hemisphere per session. Perform this protocol of the left then right hemisphere by orienting the coil laterally.
   Note: The described protocol for 10 Hz rTMS is outside international safety guidelines.
9. For intermittent theta burst stimulation (TBS), use a duty cycle of 2 sec on, 8 sec off for a total of 600 pulses per hemisphere per session. Perform this protocol of the left then right hemisphere by orienting the coil laterally, as previously described.
10. Adaptively titrate the rTMS stimulus intensity upwards from an initial value of 20% maximum stimulator intensity, to allow the patient to habituate to the pain and scalp discomfort associated with rTMS during the initial sessions. Increment the stimulation intensity by 2-5% on each train of stimulation, as tolerated.
    1. To assess tolerability, have the patient rate pain on a verbal analogue scale (VAS) from 0 to 10 (0 = no pain, 10 = limit of tolerability without emotional distress) after each train of stimulation is delivered.
11. Begin with a higher stimulation intensity on each session, using a level associated with moderate tolerability (VAS 5-6) from the previous session, until the patient is starting at the target intensity of 120% of resting motor threshold on each hemisphere. Maintain a verbal analogue scale of less than 9 throughout treatments during this titration process. Titration is typically completed in 2-5 days.
12. Monitor the patient for other adverse effects during treatment.
    Note: The most common treatment-interrupting adverse effect is a syncopal episode, arising during the first or second session of treatment in ~1% of patients. The patient may recount feeling dizzy, faint, or disoriented, and may transiently (~10 sec) lose consciousness. Regular, repeated convulsive movements or post-episode confusion lasting more than a few seconds should be absent, however. In the event of a syncopal episode, lower the headrest on the chair if possible and encourage the patient to remain still until recovered. The session may proceed if the patient is recovered and willing to go on after a few min.
13. Monitor the patient for a generalized tonic-clonic seizure during treatment.
    Note: These events are rare, and we have not observed a seizure in ~8,000 sessions of dmPFC-rTMS across >200 individual patients to date. Regular, rhythmical, vigorous convulsive movements lasting 10-40 sec, initially around 3 Hz and becoming progressively less rapid, accompanied by unresponsiveness, are suggestive of seizure rather than syncope. However, the two may be difficult to distinguish for an untrained observer.
    1. Use video monitoring during all treatments so that the episode can be reviewed by a neurologist at subsequent assessment, if necessary. In the event of such an episode, apply standard seizure first aid steps, including clearing the area of objects with the potential to cause injury, placing the patient on the ground if possible or lowering the treatment chair to the horizontal position if not, laying the patient on the left side if possible, ensuring a clear airway, and ensuring that someone remains with the patient until the seizure terminates and the person regains full alertness.
    2. Call emergency services if the seizure does not self-terminate after ~60 sec.

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
3T GE Signa HDx Scanner	GE	n/a
Visor 2.0 Neuronavigation System	ANT Neuro	n/a
MagPro R30 Stimulator	MagVenture	n/a
Cool-DB80 Coil	MagVenture	n/a