Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method

The variation of stimulated targets across the DLPFC may account for most of the efficacy heterogeneity of rTMS. This method helps in locating the effective target precisely. The differences between individual brains may lead to inaccurate stimulation target by the traditional five cm rule.

This protocol provides a strategy to acquire the individual stimulate target for each subject. This technique may help enhance the accuracy of positioning and possibly improve the treatment response of depression. Demonstrating the procedure will be Min Zhang and Xin Luo, a couple of members from my laboratory.

Begin by selecting the subgenual anterior cingulate cortex, or sgACC, as the region of interest, or ROI, with a 10-millimeter radius. Remove the white matter and cerebrospinal fluid in the ROI based on the Harvard-Oxford cortical atlas. using a gray matter probability threshold of 0.25.

Extract the average time course of the ROI. To generate the functional connectivity, or FC, map, compute Pearson's correlation coefficients between the ROI and dorsolateral prefrontal cortex, or DLPFC, in a voxel-wise manner. Normalize each correlation coefficient using Fisher's r-to-z transformation.

According to the FC map, identify the peak coordinate in DLPFC with the largest Pearson's anti-correlation coefficient with sgACC. This is the subregion of DLPFC with the strongest negative FC with sgACC, which will be later targeted in the transcranial magnetic stimulation, or TMS, treatment for the experimental group. To begin determining the resting motor threshold, or RMT, and recording the hotspot for each subject, instruct the patient to sit back and relax.

Then, put two recording electrodes on the thenar of the right hand and a reference electrode on the bony part of the wrist. Stimulate the motor hotspot with 10 consecutive stimulations with different intensities, meanwhile recording the number of thenar muscle contractions. Identify the minimum TMS intensity at which a motor-evoked potential of greater than or equal to 50 microvolts is recorded at least five times, and define it as the patient's RMT.

Assess the severity of depression using clinical scales as described in Clinical Data Collection. Perform the TMS treatment two times a day for 10 days. To create a new patient entry, select the Create New Patient option.

Input the patient's ID number or name in the text box. Then, to overlay the structural MRI images onto the navigation system, select Import patient MRI, and then import the structural image of the patient and select the image type. Create an individual head model, and define the stimulation target by first pressing the Specify MRI Fiducials button.

Place the crosshair on different spots in the MRI image as mentioned in the manuscript. Press Create Head Model, and select Manual Brain Segmentation. And adjust the threshold of the scalp, the lower brain, and the upper brain.

Click on Define Target to proceed. Select the Target Marker page, and click Go to MRI Coordinates to input the coordinate of the treatment target as identified previously, and then press Go to. Press Add Marker to name the point.

To calibrate the coil, first click Proceed to Neuronavigation. In the text box, select the right type of tools to be used in the treatment. Ensure all the tools of reference are in the view of the infrared camera.

Then press Validate Coil, and put the tip of the pointer on the marked coil point. Press Validate when the indicator of each tool turns green. Select the patient's name or ID on the Select Patient page.

Then, click on Select Targets on the next page. Choose Read target markers to browse the file of targets. Import the file, and select the target.

Click on Define Coordinate System. Put a headband with a reference tool on the patient. Ensure the coil tracker and the reference tool are in the vision of the navigation system.

Place the pointer's tip on nasion and both tragi in turn. Press the green button on the remote control each time the indicator of a marker turns green. Continuously move the pointer's tip over the top of the head.

Press the button on the remote control to continue. Press Neuronavigation, and on the Active Coil page, set the stimulation intensity to 100%RMT. Choose Stimulate at targets to see the target on the head model online.

When the coil matches the target crosshair and the indicator text turns green, stimulate. Prepare and start the treatment directly from the coil calibration step if the patient's entry has been created before. Conduct follow-up assessments on day one, day 28, and day 56 after the whole treatment course.

The response rate among 23 MDD patients was found to be 90.48%19 of 22 participants met the remission criteria in the intent-to-treat analysis. The scores of clinical assessments post-TMS treatment were calculated for all the patients. By precisely locating the effective target of rTMS, this technique may improve the treatment of depression and also provide new ideas for treatment of treatment-resistant depression.