Concurrent TMS-fMRI: Technical Challenges, Developments, and Overview of Previous Studies

Abstract

Transcranial magnetic stimulation (TMS) is a promising treatment modality for psychiatric and neurological disorders. Repetitive TMS (rTMS) is widely used for the treatment of psychiatric and neurological diseases, such as depression, motor stroke, and neuropathic pain. However, the underlying mechanisms of rTMS-mediated neuronal modulation are not fully understood. In this respect, concurrent or simultaneous TMS-fMRI, in which TMS is applied during functional magnetic resonance imaging (fMRI), is a viable tool to gain insights, as it enables an investigation of the immediate effects of TMS. Concurrent application of TMS during neuroimaging usually causes severe artifacts due to magnetic field inhomogeneities induced by TMS. However, by carefully interleaving the TMS pulses with MR signal acquisition in the way that these are far enough apart, we can avoid any image distortions. While the very first feasibility studies date back to the 1990s, recent developments in coil hardware and acquisition techniques have boosted the number of TMS-fMRI applications. As such, a concurrent application requires expertise in both TMS and MRI mechanisms and sequencing, and the hurdle of initial technical set up and maintenance remains high. This review gives a comprehensive overview of concurrent TMS-fMRI techniques by collecting (1) basic information, (2) technical challenges and developments, (3) an overview of findings reported so far using concurrent TMS-fMRI, and (4) current limitations and our suggestions for improvement. By sharing this review, we hope to attract the interest of researchers from various backgrounds and create an educational knowledge base.

Keywords: concurrent TMS-fMRI; functional MRI (fMRI); interleaved TMS-fMRI; review; transcranial magnetic stimulation (TMS).

Figure 1

Example of TMS-fMRI set up. (A) This particular example of TMS-fMRI set up includes MR compatible TMS coils (Magventure, Farum, Denmark), MR coils (16), neuronavigation system (Localite, Bonn, Germany), and a BrainAmp ExG MR amplifier (BrainProducts, Gilching, Germany) for electromyographic (EMG) measurements to determine motor threshold (MT). (B) TMS coil is mounted on a holder which goes in the bore of the scanner. The holder system is attached to the scanner bed so that it moves together. The MR head coil, in this example, is two thin and flat seven channel coils. One is attached below the TMS coil, and the other is stabilized on the other side of the head using a vacuum pillow. Two trackers on the forehead and coil enable neuronavigation. (C) EMG amplifier continues to record the motor evoked potential (MEP) and the neuronavigation system tracks the TMS coil location throughout the scanning session. (D) TMS device remains in the technical room as it is ferromagnetic. The TMS coil is connected to the MRI room by a 6-m cable through a hole in the wall. The cable is covered with a filter tube, and a filter box is installed along the cable. (E) Neuronavigation system shows the location of the stimulation. The red dot is calculated with a coordinate that defines the target point. By defining the coil orientation, it calculates the entering point which is the green dot with the green bar showing the coil handle orientation. The pink pins show the actual stimulation location, which is recorded each time a TMS pulse is applied during the TMS-fMRI session. These pink pins can be recorded during the concurrent TMS-fMRI session and can be used for the post-analysis as far as the head and coil trackers are visible in the MR bore as shown in panel (C).

Figure 2

Example of concurrent TMS-fMRI protocols. There are three possible ways to apply TMS pulses during fMRI simultaneously. (A) A method enabling TMS to interfere with EPI slices. Perturbed EPI slices (indicated by an orange cross) are sacrificed and replaced by slice interpolation, typically from the volumes before and after the volume of interest (indicated by orange EPI slices). Advantages: High flexibility to stimulate at any time regardless of EPI timing. Disadvantages: It requires a high level of post-processing capabilities to detect the damaged EPI slices and replace them. (B) A method to insert a gap time between EPI slices and apply TMS pulses meanwhile. Advantages: No EPI slices are sacrificed. Disadvantages: The number of stimulations is limited as it needs to fit in the gap time. Hence, the whole TMS-fMRI protocol tends to be longer. (C) A method to interleave TMS pulses with EPI slices. Advantages: It allows for continuous stimulation which is often used as a therapeutic protocol. Disadvantages: Reliable hardware and software are essential as the pulses must be controlled precisely.