MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

The overall goal of the following experiment is to stimulate the dorsal medial prefrontal cortex using repetitive transcranial magnetic stimulation or RTMS as a treatment for major depression. This is achieved by first acquiring an anatomical MRI for real-time neuronavigation during stimulation. As a second step resting motor threshold is assessed, which identifies the patient's stimulation intensity for RTMS treatment.

Next RTMS is performed to the D-M-P-F-C in order to reduce the severity of depression. The results show a significant reduction of depressive severity in open-label pilot studies based on self-reported and clinical administered questionnaires for depression. So the method of dors medial repetitive transcranial magnetic simulation or M-P-F-C-R-T-M-S is most commonly used for the treatment of major depression and for research into the basic mechanisms of major depression.

However, it also has applications and other psychiatric conditions including eating disorders, obsessive compulsive disorder, and post-traumatic stress disorder demonstrating the procedure today will be a couple of members from our lab will have vanity and far oak To begin select patients based on the set of inclusion and exclusion criteria described in the accompanying text protocol exclude patients with potential contraindications to RTMS or MRI prior to treatment. Acquire a high resolution MRI exam that can be reconstructed in three DA three Tesla scanner, equipped with an eight channel phased array. Head coil is used here, but any scanner capable of acquiring high resolution images can be used.

Next, prepare for MRI guidance using a neuro navigation system Here, the visor 2.0 Neuronavigation system is used. First, register these two segments into standard stereotactic space, such as rack and turno space. Then segment the anatomical MRI into separate scalp and brain components.

The patient's brain and scalp will be registered to stereotactic coordinates for individualized coil placement during treatment. Once the patient is comfortably seated, place the headband with a marker clip around the patient's head. The marker clip should sit above the bridge of the patient's nose.

Then load the pre-processed anatomical scans to the NEURONAVIGATION program and turn on the camera. Now using a neuronavigation pen, highlight each scalp target point on the patient. The movements made with a neuronavigation pen will be projected on the monitor in the form of red lines.

Next, the patient's motor thresholds or the minimum intensity needed to globally excite the motor pathway need to be assessed prior to the RTMS treatment. For this step, begin by having the patient's lower limbs extended and supported from below, using a stool or a chair equipped with an extensible leg rest, use a stimulator equipped with a fluid cooled coil. Also use an angled or double cone coil for deeper pulse penetration into medial areas.

Winding should be angled at 120 degrees to allow deeper penetration of the pulses. Perform motor thresholding separately for the left and right hemispheres. Using neuro navigation.

Target the patient's medial primary motor cortex by placing the coil vertex over the sagittal fissure. 0.5 to 1.0 centimeters anterior to the central sulcus. Orient the coil laterally to direct RTMS evoked current flow to the desired hemisphere.

For example, orient the coil with a handle pointing right words to direct current flow toward the left hemisphere. Observe the contralateral lower limb for movements during the following procedure. Determine threshold and elicited motor movement by observing the halluc longest muscle of the big toe.

Begin by stimulating at 55%of maximum machine intensity. Then depending on whether a response is observed, adjust upwards or downwards in increments of about 5%Reduce the increment size steadily to approximately 1%as the motor threshold is approached. Stimulate no more frequently than 0.2 hertz to avoid inhibitory or excitatory effects over time.

To perform a course of NeuroD RTMS to the dorsal medial prefrontal cortex, use a total of 20 to 30 daily sessions over four to six weeks. Again, use the 120 degree angled fluid cooled coil and parameters described here for stimulation in each treatment session. First, ensure that the patient and operator wear earplugs or other hearing protection during treatment.

Then place the coil over the dorsal medial prefrontal cortex. Target under MRI guidance using the neuro navigation system for 10 hertz stimulation. Use a duty cycle of five seconds on 10 seconds off for a total of 60 trains or 3000 pulses per hemisphere per session.

Perform this protocol on the left hemisphere, then on the right by orienting the co laterally. If performing treatment with theta birth stimulation, use a duty cycle of two seconds on eight seconds off for a total of 600 pulses per hemisphere per session. Also, perform this protocol on the left than right hemisphere.

During initial sessions, adaptively titrate upwards from an initial value of 20%maximum stimulator intensity. Titration of the RTMS stimulus intensity is to allow the patient to habituate to the pain and scalp discomfort associated with stimulation. Adjust stimulation intensity by two to 5%on each train of stimulation as tolerated after each train of stimulation is delivered.

Assess tolerability by having the patient rate pain on a verbal analog. Scale from zero to 10 with zero meaning no pain, and 10 being the limit of tolerability without emotional distress For each session. Begin with a higher stimulation intensity using a level associated with moderate tolerability from the previous session.

Do this until the patient can start at the target intensity of 120%resting motor threshold for each hemisphere. Be sure to maintain a verbal analog scale of less than nine throughout treatments during this titration process. Typically completed in two to five days.

Monitor the patient for any adverse effects during treatment. The most common treatment interrupting adverse effect is a syncopal episode arising during the first or second session of treatment in approximately 1%of patients. Although these events are rare.

Also, monitor the patient for seizure activity. Use video monitoring so that an episode can be reviewed by a neurologist at subsequent assessment if necessary. This figure displays the pre and post-treatment Hamilton depression rating percent improvement in a previously published case series among all subjects pre-treatment score was significantly decreased.

Post RTMS treatment. This figure displays the pre and post-treatment Beck depression inventory percent improvement in the same case series score significantly decreased post RTMS Dorsi medial RTMS using the 10 hertz protocol is just one approach to stimulation. There are lots of other approaches which are currently in development and offer some exciting potential to develop into new kinds of treatments.

These include approaches like inhibitory stimulation, stimulation of areas of the brain, other than the dors medial prefrontal cortex, and even accelerated protocols using multiple sessions per day to accelerate their treatment response. These kinds of approaches could lead to new treatments and more powerful treatments for major depression and other kinds of psychiatric conditions.