Mapping the After-effects of Theta Burst Stimulation on the Human Auditory Cortex with Functional Imaging

The overall goal of this procedure is to combine functional brain imaging with transcranial magnetic stimulation to investigate the auditory cortex. This is accomplished by first carrying out a functional Mr.Localizer in order to identify the network associated with an auditory task. Second, define the stimulation target based on data from the functional Mr.Localizer.

Next, carry out a functional MR scan to measure activity in the auditory cortex prior to stimulation. Then use NEURONAVIGATION tools in order to position the TMS coil relative to the individual anatomy and function of the participant. This is done while the subject is lying on the scanner bed.

In order to avoid displacing the participant back and forth from the scanner room, the final step is to slide the participant back into the scanner bore as quickly as possible and start the FMRI acquisition. Ultimately, FMRI can map TMS induced effects. The data showed that after TMS there is a functional reorganization in the auditory network.

TMS is a unique tool for investigating causal relationships between specific brain areas and cognitive functions. However, its interpretation is limited, but lack of information regarding the location and nature of changes in brain activity induced by TMS. This is why we decided to combine TMS with functional imaging in order to determine the functional changes induced by TMS.

The difference between our study and previous studies is that we carry out TMS inside the scanner room in the standard offline TMS and FMI. The participant has to leave the MRI room, go to another room in order to receive TMS, and then come back as fast as possible. For the second FMRI session this back, this back and forth can add viability to brain changes and used by TMS in our protocol.

The head position remains relatively stable, which can lead to a greater accuracy when we compare pre and post FM RI data. And in addition, the TMS and used effects will be mapped more quickly. This protocol is divided in a two day session.

The first day consists of an FMRI LOCALIZER session with an anatomical and a functional scan to define the areas to be targeted with TMS. The second day consists of FMRI sessions, both pre and post TMS on the first day have the participant practice the melody discrimination task outside the scanner. In this task, the subject indicates if two consecutive five note melodies are the same or different.

A non-discrimination auditory control task is also included in which the subject hears to equal length patterns of five notes all at the same pitch of C five and presses a button after the second tone. Next, begin the MRI session by acquiring a high resolution MR.Anatomical image. Then acquire functional images using a gradient echo EPI pulse sequence and a sparse sampling paradigm to minimize any bold effect or auditory masking due to MRI scanning.

Noise after scanning is complete. Define the subject stimulation site using both anatomical and functional landmarks. Be aware that TMS is limited regarding the depth of the stimulation site due to the attenuation of the electric field strength and depth and cannot expect to reach areas deeper than three centimeters.

It is crucial to use similar landmarks for each participant despite differences in anatomy and function between individuals. Therefore, use anatomical landmarks to locate heschel's gyrus as defined by Harvard Oxford structural Atlas masks. The mask is shown here in green, then defined the TMS target by finding the peak of activation within heschel's gyrus, which is shown here by the blue dot.

Also locate the vertex as a site to control for non-specific effects of TMS such as acoustic and somatosensory artifacts. This is defined anatomically as a point midway between the inion and the bridge of the nose and equidistant from the right and left interal notches. Note that the order of sight of stimulation should be counterbalanced across individuals.

On the day of the TMS experiment. Set up all equipment. Starting with the Frameless stereo taxi system.

The computer system must be positioned outside of the scanner room adjacent to the door, which will be open during TMS application. The systems registration tools and trackers are MR compatible, as well as a multi-joint arm. The infrared camera used here is not MR compatible and therefore must be positioned two meters away from the scanner bed inside the scanner room near the scanner door.

The TMS stimulator system should be located in a room adjacent to the MRI scanner room. An MRI compatible TMS coil will be used in the scanner room connected to the TMS system via a seven meter cable through an RF filter tube load, the participant's anatomical and functional images and the stimulation targets into the stereotactic software package. Here we'll be targeting the participant's right heschel's gyrus prior to beginning the scan.

Have the subject fill out an MR screening form and remove all metal. Then start MR Acquisition with anatomical and functional scans identical to the one carried out in the localizer session. Next, slide the scanner bed out and keep the body platform raised during the whole TMS session.

Remove the upper Mr.Head coil and fix the headband and tracker set onto the participant's head mount the multi-joint arm to the scanner bed. Then fix the MR compatible TMS coil onto the arm. Verify that all the trackers and the coil are in the field of view of the camera Here.

The camera is slightly to the right side of the participant to enable an easier tracking of the coil displacement. When targeting the right hemisphere, calibrate your subject's head with the stereo taxi tools, coregister the tip of the nose, the nas, and the tragus of both ears with the same landmarks on the anatomical data. Two experimenters are needed for this.

Step one at the participant's head and at the computer to perform the registration on the computer. Next position, the MR compatible TMS coil tangential to the scalp with the coil trackers directed towards the infrared camera. The coil should be oriented with the handle pointing backward and parallel to the midline.

Fix the coil position using the screws on the multi-joint arm. Now turn on the TMS system and begin stimulation. TMS should be applied following a patterned protocol such as continuous theta birth stimulation consisting of three pulses at 50 hertz, repeated at five hertz for 40 seconds.

This protocol has been shown to modulate cortical plasticity for a duration up to 30 minutes after stimulation cessation in healthy populations. Once stimulation is complete, it is important to place the subject back in the scanner as quickly as possible. Remove all TMS equipment and slide the participant's head into the Mr.Head coil.

Ensure your scan sequences are prepared and ready to go with number and duration of localizer scans reduced to a minimum. Since the effects of RTMS are transitory, the final scanning session should begin with the functional scan. Again, conduct FMRI during the 12 minute run of the melody task.

After the functional scan is complete, finish with an anatomical scan After the experiment. Conduct analysis of FMRI data separately for both the pre and post T-M-S-F-M-R-I session for each FMRI session. Contrast between the melodies and the auditory control task.

Then to evaluate differences between pre and post T-M-S-F-M-R-I sessions, perform a random effect analysis using a student's paired T-test. Here we see results of the contrast melody discrimination minus auditory control trials for a single participant in the pre T-M-S-F-M-R-I session and in the post T-M-S-F-M-R-I session for both pre and post T-M-S-F-M-R-I sessions coordinates are displayed in MNI 1 52 standard space to show changes in the left hemisphere contralateral to the site of stimulation, including heschel's gyrus. Here we can see results of the contrast post minus pre T-M-S-F-M-R-I sessions using a student's paired T-test.

The data suggests that CTBS targeting the right heschel's gyrus induces an increase in signal in the contralateral auditory cortex and also in other contralateral areas. In addition, we also observe changes in functional connectivity between auditory cortices in the two hemispheres. After watching this video, you should have a good understanding of how to use TMS neuronavigation equipment to target specific brain areas and how to perform TMS inside an ML environment.

This procedure enables researchers to map the TMS induced effects on auditory cortex using FMRI. However, the procedure can also be used to target other regions of interest, such as frontal or parietal areas.