Continuous Theta Burst Stimulation to Reduce Responses to Ideological Threats

Abstract

Source: Holbrook, C., et al. Continuous Theta Burst Stimulation of the Posterior Medial Frontal Cortex to Experimentally Reduce Ideological Threat Responses. J. Vis. Exp. (2018)

This video demonstrates the application of continuous theta burst stimulation (cTBS) to modulate responses to ideological threats. Electromyography (EMG) electrodes record motor signals, while a magnetic coil stimulates the primary motor cortex to determine the active motor threshold (aMT). The coil is then repositioned over the posterior medial frontal cortex (pMFC) for targeted stimulation. Prolonged cTBS reduces excitatory signaling and enhances pMFC inhibition, temporarily decreasing responsiveness to ideological threats.

Protocol

1. Continuous Theta Burst Stimulation (cTBS) Procedure
   1. Seat the participant in a comfortable position and fit a grid-marked swim cap to his/her head. Use earplugs if needed to increase the comfort of the subject. Attach two differential parallel-bar electromyography (EMG)-recording electrodes, centered over the belly of the tibialis anterior muscle, after cleaning the skin over the muscle thoroughly. Attach a third, ground electrode to the skin over a bone somewhere else on the hand or arm.
   2. On the swim cap, measure and mark the center location (Cz) on the subject's head.
      1. If using neuronavigation (recommended), launch the neuronavigation software and follow the software's procedure for localizing the subject's head. Have the subject rest comfortably and begin recording the EMG electrode output to software that will filter and display the signal.
   3. Perform thresholding on the primary motor cortex. With a double-cone coil (110 mm), place the center of the coil over the motor cortex, held tangential to the scalp surface. Apply single-pulse transcranial magnetic stimulation (TMS) at 50% of the maximum stimulus output (MSO) and observe whether a motor-evoked potential (MEP) was present in the EMG signal following the stimulation.
      1. If no MEP is seen following the stimulation, reposition the coil 1 cm away in any direction and try the stimulation again. Wait at least 6–10 s between stimulations in order for the neurons to completely recover. Continue moving the coil 1 cm at a time, marking on the cap the stimulation sites that result in an MEP of 50 mV or greater.
      2. If no MEPs are seen after trying many locations, increase the stimulation intensity by 5% at a time until MEPs are observed.
      3. Multiple nearby locations on the grid may elicit reliable MEPs. If this is the case, stimulate each of these locations at intensities decreasing by 1% at a time, until only one location remains that elicits reliable MEPs.
   4. To determine the active motor threshold (aMT), have the subject slightly contract the target muscle. Stimulate the located region for 10 repetitions, separated by ~7 s, at decreasing intensities, until a corresponding observable twitch in the hand muscle no longer occurs for 50% of the stimulations (5 out of 10). The threshold is the lowest intensity that elicits 5/10 twitches.
      1. Navigate the coil to the specified location on the cap corresponding to the brain region of interest. If the double-cone coil to be used has a directionality of current flow, and if the target region is lateralized, orient the coil laterally so that the current flow is directed toward the hemisphere to be stimulated (e.g., a rightward current flow for a right hemisphere target).
         1. If using neuronavigation, locate the coordinates for the region of interest (posterior medial frontal cortex, or pMFC) at Montreal Neurological Institute (MNI) coordinates [8, 16, 52] and mark this point on the system. Use the guiding software to target the region with the coil.
         2. If neuronavigation is unavailable due to logistical or financial constraints (as was the case in the example experiment), determine the location of the pMFC for each subject's head using the international 10–20 system. Place the coil 3.75 cm anterior to the motor cortex.
   5. Apply cTBS as follows: three pulses at 50 Hz repeated at 200 ms intervals for 40 s, totaling 600 pulses.
   6. If the participant is in the sham group, apply cTBS at only 10% of the maximal stimulation output.

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Isopropyl alcohol
Ear plugs
Adult swim cap	Sprint Aquatics	304
MobiMini 2-channel recording system	TMSi
EMG electrodes	TMSi
Covidien Kendall disposable surface electrodes (24 mm)	Bio-medical	H124SG
Magstim Rapid2 TMS device	Magstim
D70 figure-of-eight coil	Magstim
Visor2 Neuronavigation software	ANT Neuro