Transcranial Magnetic Stimulation for Investigating Causal Brain-behavioral Relationships and their Time Course

The overall goal of the following procedure is to investigate causal relationships between brain and behavior. The first step is to prepare the TMS experiment by choosing the stimulation parameters, tasks, and localization method. The second step is to localize the stimulation site, customizing it to each individual in order to ensure that the correct brain site is targeted.

The next step is to conduct the main TMS experiment using either a virtual lesion or chronometric approach in order to test whether stimulation affects task performance. Results that demonstrate an effect of TMS on behavioral measures, typically in the form of longer reaction times in comparison to performance in control conditions indicate that the stipulated brain region is a necessary component of normal task performance. The main advantage of TMS over neuroimaging methods is that it offers the opportunity to disrupt neuro information processing and measure its effects on behavior.

In other words, it offers more than a simple correlation, but allows one to draw causal inferences between brain and behavior. In addition, TMS also offers advantages over more traditional causal methods, such as patient research, because it provides a non-invasive alternative approach that allows us to produce virtual lesions, which are temporary, reversible, and more spatially precise Individuals new to this methodology may struggle due to the large number of free parameters that need to be chosen in order to make an experiment successful. These include things like the duration and intensity of the stimulation, the way the stimulation sites are localized, and even seemingly more minor things like the orientation of the actual coil.

As a result, extensive pilot testing is normally necessary in order to determine which parameters work for your particular experiment. Prior to the TMS session, acquire a high resolution T one weighted MRI scan of the participant. Include the fiducial points for the frameless stereo taxii system, the tip of the nose, the bridge of the nose, and the notch above the tragus of each ear.

Load the scan into a frameless, stereo taxii system and mark the fiducial points and the stimulation sites on the participant's image. Keep the stimulation sites at least 10 millimeters away from each other at the start of the TMS session. First, explain the experimental procedures to the participant so they can give informed consent.

Second, ask the participant to complete a TMS safety screening form approved by the Institutional Review Board to make sure they can receive TMS Permanent contraindications to TMS include a, a family or personal history of epilepsy, a clinical diagnosis of a psychiatric or a neurological disorder, or any kind of implanted medical device like a cochlear implant or a pacemaker. Not following TMS safety guidelines puts the participant at risk of either seizure or damage to the implanted medical devices. Once the screening is complete, place the subject tracker on the participant's head.

Then using the tracker as a reference, touch each fiducial point on the participant's head with a pointer that comes with the stereo taxi system. Save the corresponding coordinates to calibrate the participant's head with the MRI image. Be sure to check the quality of registration and repeat the process as needed.

Now is also a good time to ask the participant to put in earplugs. Next, set up the TMS equipment according to the protocol. This example uses standard biphasic stimulation in conjunction with a figure of eight shaped coil.

The frequency of stimulation chosen here is 10 hertz and is set to a duration of 500 milliseconds, which is a common choice, common choice. The intensity chosen is 55%of the maximum output of the stimulator. Typically, 50 to 70%of maximum is the right power to use.

Now, introduce the participant to the stimulation before conducting the experiment First, demonstrate it on the researcher's arm. Then on the participant's arm. Next, demonstrate the stimulation on each testing site.

The coil should be oriented tangential to the scalp, such that the line of the maximum magnetic flux intersects the stimulated site. Monitor the position of the coil throughout the experiment. In some cases, this can lead to discomfort that can be ameliorated by adjusting the orientation of the coil.

If the participant does not tolerate the stimulation, then testing must be stopped. But this is not common. Use a localizer task that taps into the cognitive function of interest and has a measurable behavior such as reaction, time, accuracy, or eye movements.

Create multiple versions of the task to avoid repeating the stimuli in the first practice session. Let the participant practice the task without stimulation. In the next practice session, introduce TMS pseudo randomly to 50%of the trials after the practice sessions.

Conduct the localization task on the first stimulation site. Immediately check if TMS affected the participant's performance by, for example, producing longer reaction times compared to the no TMS condition. Choose sites where TMS produces a consistent, reasonable, and site-specific effect.

Sometimes an incorrect site will actually facilitate responses relative to no stimulation due to inters sensory facilitation. In addition, large TMS effects are usually artifactual and required retesting. Test multiple sites back to back in the same session.

And be sure to counterbalance the order that sites are stimulated across participants after localization, and in the same session, run the main experiment using the stimulation site that was functionally localized. Use a different task from the one used for localization, but one that shares the key process of interest. For example, a rhyme judgment task for localization and a homophone judgment task for the main experiment.

Both tasks here require phonological processing of written words, although the specific task demands and stimuli differ to demonstrate functional specificity of the testing site include a task that does not include the process of interest. Also, test a control site to demonstrate anatomical specificity of the effect. Now, conduct either a traditional virtual lesion experiment using the same TMS parameters as during localization and or a chronometric TMS experiment, which replaces the train of pulses used during localization with a single or double pulse delivered at different time points.

This investigation tested whether the left supramarginal gyrus is causally involved in processing the sounds of words. Five pulses of repetitive TMS delivered at 10 hertz and 55%of maximum intensity were delivered to the super marginal gyrus. During three tasks, each with 100 trials, a phonological task focused attention on the sounds of words.

Trials with TMS have significantly longer reaction times than trials without TMS indicating that TMS disrupted phonological processing a semantic control task focused on the meaning of words. Trials with TMS do not differ significantly from the trials without TMS indicating that TMS did not significantly disrupt semantic processing. TMS to the super marginal gyrus selectively affected phonological, but not semantic processing.

An additional control task presented pairs of consonant letter strings and asked whether they were identical. Again, TMS did not affect performance on this control task altogether. Stimulation of the left SMG selectively interfered with processing the sounds of words.

Next, the temporal dynamics of SMG involvement in phonological processing was investigated using the same task. Double pulses of TMS were delivered at five different time windows after stimulus onset. When compared to the baseline condition, there was a significant increase in reaction times when TMS was delivered in the three later time windows.

The results suggest SMG engagement in phonological processing begins early and is sustained for about 100 milliseconds. It's very important to remember that TMS protocols have a large number of free parameters, and choosing the optimal parameters is crucial to produce robust effects. So each TMS experiment requires extensive piloting.

Once all the parameters are chosen, A TMS experiment can typically last around an hour. But this depends, of course on how long it takes the participant to get familiarized with ATM S, as well as how long it takes to successfully localize A TMS site. Most importantly, safety considerations need to be taken into account whenever you're designing A TMS experiment.

And this has important implications for things like the number of trials that a participant's exposed to, the number of conditions that you can test, and the number of sites that you can test in a day.