The Use of Magnetic Resonance Spectroscopy as a Tool for the Measurement of Bi-hemispheric Transcranial Electric Stimulation Effects on Primary Motor Cortex Metabolism

The overall goal of this procedure is to combine transcranial direct current stimulation with proton MRS measurements to investigate the effects of bilateral stimulation on primary motor cortex metabolism. This is accomplished by first carefully positioning the stimulating electrodes over the target area and securing them to the participant's scalp while the participant is outside the scanner. After determining the position of the MRS voxel using an anatomical scan of the participant brain, four blocks of 64 metabolite scans are run with an MRS mega press sequence.

Next, with the participants still in the MRI scanner, bilateral stimulation of the primary motor cortex is performed for 20 minutes at an intensity of one milliamp. Here, the final step is to run the same metabolite scans as the pre transcranial direct current stimulation or pre TDCS scan. Ultimately combining transcranial direct current stimulation with magnetic resonance spectroscopy is used to show modulations in GABA and GLX concentrations associated with bilateral stimulation of the primary motor cortex.

This method can help answer key questions in the neuromodulation field, such as which neurotransmitters are affected by specific stimulation protocols. How focal are the effects of stimulation? Does bilateral stimulation result in larger effects than unilateral stimulation?

And how long are the effects of TDCS? The implications of this technique are also clinical because it has been shown that TDCS can alleviate symptoms of depression. A better understanding of how TDCS works could help better define stimulation parameters, and could also lead to individualized therapy.

It could also serve as a way to better predict which patients will respond to the technique and which will not. Begin this protocol with preparatory steps as described in the text protocol, use a multimeter to verify the proper functioning of the electrode cable and resistance. After determining the positions of the electrodes, move as much hair as possible away from the targeted areas that will be stimulated.

Apply an EEG type exfoliating gel with a cotton swab to clean the targeted areas. Further clean the targeted areas with a 70%isopropyl alcohol and pumice prepping pad to enhance electrode contact. Then generously cover the entire electrode with an EEG type conductive paste.

Ensure that the paste is approximately five millimeters thick across the entire surface. Make sure the entire rubber area is covered with paste. Lightly wet the target areas and the conductive paste on the electrodes with the saline solution.

Position the electrodes as demonstrated here, and press the electrodes firmly onto the targeted areas. Place a rubber band around the head of the participant to ensure optimal stability of the electrodes. Adjust it in such a way that the participant will experience no pain or discomfort during the scanning session.

Then turn on the transcranial direct current stimulation device and load the test stimulation settings as described in the text protocol. Press button one to start the stimulation. The display will show the impedance level and automatically stop if it reaches more than 20 kilo ohms.

If the impedance level is over 20 kilo ohms, unplug the electrode wires from the inner box and verify the placement of the electrodes. Redo the test stimulation when a good level of impedance is reached, and when the test stimulation is over, unplug the electrodes from the inner box. Place the TDCS device and the outer box in the scanner control room.

Plug the outer box wires into the TDCS device and then plug the long box cable into the outer box. Run the TDCS box cable from the scanner control room into the magnetic resonance imaging or MRI room. Make sure to run this cable as straight as possible, avoiding any kinks or loops along the wall of the MRI room.

Towards the back of the MRI scanner. Put multiple MR compatible sandbags on the cable to ensure its stability. Bring the inner box into the MRI room and plug the long box cable into it.

Begin MRI scan preparation with instructions to the participant as well as positioning of the participant in the scanner as described in the text protocol, use medical tape to stabilize the electrode cable on the right side of the back of the coil. Plug the electrode wires located inside the scanner into the TDCS inner box. Put the inner box on the right side of the scanner with the sandbag on it for maximal stability.

Move the table back into its final position. Keep the TDCS turned on and the electrodes plugged into the outer box for the entire MRI session. For the pre T-D-C-S-M-R-S session, run a localizer sequence to acquire images needed to verify the proper positioning of the head, and to compare to a second localizer, which will be acquired at the end of the session to check for overall movement.

Then acquire anatomical T one weighted MP rage images for the positioning of the M1 voxel and detection of possible structural abnormalities. Next, perform a multiplanar reconstruction of the images in planes that are more appropriate for visualization of the spectroscopy volume of interest, or VOI first in the 3D card, browse the MP rage raw images. Then from the creating parallel ranges window, select axial two by two.

Adjust the position of the parallel lines and click on save to create the axial orthogonal view from the creating parallel ranges window, select coronal two by two. Adjust the position of the parallel lines and click on save to create the coronal orthogonal view. Locate the left M1 anatomical landmarks on the three orientation slices.

Then position the VOI on the area without any angulation relative to the scanner axis. Acquire the line width scan. Then open spectroscopy card to measure water line width on the real part of the signal from this line width scan.

Load the line with raw data from the browser. Then load the line width measurement protocol. Next, adjust the phase using the scanner software interactive post-processing tools.

Select the phase correction section and adjust the phase for the baseline with the cursor. In order to reduce the line width, run the fastest map sequence three times. Repeat the line width scan and the line width measurement.

Note the final water line width. Next start four blocks of 64 metabolite scans with the mega press sequence where vapor OVS and individual storage of FIS are enabled. Acquire a water reference using only the mega press sequence without mega water suppression with vapor suppression set to only RF off, and with a delta measurement at zero PPM.

The water reference scan should include a single block of four metabolite scans instead of 64. To begin, inform the participant that the TDCS stimulation will start and that the scanner will be silent for the entire stimulation. Then select one of the two previously programmed parameters according to the condition and start the stimulation.

Keep track of the impedance and voltage during the 20 minutes of stimulation. When the stimulation is over, notify the participant that the post T-D-C-S-M-R-S session will begin. Do not turn off the TDCS device for the post T-D-C-S-M-R-S session.

Run the same metabolite scans as the pre TDCS scan, but double the blocks of acquisition to acquire the metabolites at two different time points. Post TDCS as with the pre TDCS session, acquire a water reference scan using the same parameters. Finish the session with a localizer sequence.

Access the viewing card and go to the browser menu. Select the first and second localizer raw images. Load the images in the viewing card to compare both images.

Then visually compare the images with the localizer acquired at the beginning of the scanning session as an index of head movement. Finally, export data in the DICOM format through the server. See the text protocol for data analysis shown here is the position of the volume of interest in the primary motor cortex where all MRS measures were taken.

A 3D shows a clear representation of the TDCS electrodes positioned on the scalp over the putative primary motor cortex representative edit off and different spectra acquired in M1 are shown peaks corresponding to GLX GABA plus macromolecules, as well as NAA can be clearly seen. The percentage of change between the MRS acquisition, pre TDCS and post TDCS for the three different conditions in a single participant is shown. Results from the post TDCS session are separated into two time points.

To illustrate the evolution of change over time, there is no notable modulation for the percentage of change in GLX in sham stimulation and bilateral stimulation.One. A slight reduction of the GLX concentration is observed in the second time point following stimulation in bilateral stimulation.Two. GABA concentration displays no notable modulation in sham stimulation or bilateral stimulation.Two.

In contrast, a notable increase of GABA concentration is seen in the second time point after bilateral stimulation one Once mastered. This technique can be done in two hours if it is performed properly. After watching this video, you should have a good understanding on how to measure the effects of TTC S on specific brain metabolites such as GABA and glutamate.