Study Design for Navigated Repetitive Transcranial Magnetic Stimulation for Speech Cortical Mapping

Our protocol is noninvasive and comparable to the invasive gold standard. Thus, it can assist in selecting patients in designing the surgery and speed up the direct cortical stimulation conducted during the surgery. This technique allows detailed speech cortical mapping and flexible changes of the task and the stimulation parameters.

It can be also applied to a healthy population and adjusted for any kind of language task. Our protocol can replace direct cortical stimulation in cases where it cannot be performed and it can also be applied when identifying language network nodes to be stimulated in stroke patients. It is challenging to decide which parameters to change first to induce more naming errors.

It's advisable to change one parameter at a time and to get prior spatial and temporal information from different imaging modalities such as MEG, EEG, or FMRI. To begin, familiarize the subject with the printed or digital format images before the baseline object naming task. Use images of standardized and normalized color frequently seen in an everyday environment with minimal synonyms and high name agreement.

Let the subject practice with the images before the session starts. The subject could also practice at home. Next, attach an accelerometer on the skin above the larynx and the vocal cords to record the speech onset.

Present the images one by one to the subject on a screen placed at a 0.5 to 1 meter distance and ask them to name the images allowed without stimulation.Pinchers. A cake. Adjust the inter-picture interval, IPI, to make the task slightly challenging for each subject starting with 2, 500 milliseconds and varying between 1, 500 to 4, 000 milliseconds.

If more errors occur during the baseline naming task, increase the IPI in steps of 200 to 300 milliseconds. If the task is too easy, decrease the IPI in steps of 200 to 300 milliseconds. For the actual speech mapping session with navigated repetitive TMS, omit the images that during the baseline testing were not trained adequately, not named correctly, not named clearly, not articulated correctly, named with delay or hesitance or seemed difficult for the subject.

Run the baseline naming task three times and adjust the IPI if performance is unsatisfactory. Before starting the stimulation, check that the induced electric field values are approximately similar in the different speech-related areas in both hemispheres. Adjust the cortical depth if needed and ensure the coil center is not in the air.

Start with a default picture to TMS interval, PTI, of 300 milliseconds or use a 0 to 400 milliseconds PTI. A PTI above 150 milliseconds is preferred to optimize the overlap of stimulation with language processing. Start with five pulses at a five hertz rate at a cortical area unrelated to speech processing so that the subject gets used to the stimulation-induced sensation.

Then move the coil to the expected speech-related areas. Keep the coil in the same position until the pulse train is over and the subject's naming is completed. Focus on the subject's performance.

If there is no error, move on to the next locus. If an error or even a hesitation is observed, continue stimulating that site for an additional two to three navigated repetitive TMS trains, and then move on. But remember the site for possible later restimulation.

Make small coil adjustments when even a slight error is detected, like minor hesitation or a louder voice during the naming due to an increased effort to provoke clearer errors. Avoid repeating stimulation on the same site for more than five consecutive trains. Continue with other cortical sites and revisit the site later.

If repeated errors appear at several stimulated locations, lift the coil in the air above the scalp and check if errors still occur. If errors still occur, take a break and wait until the naming returns to normal. Then stimulate in blocks of 7 to 10 minutes continuously and have a 2 to 5 minute break in between.

Stimulate all the possibly related anatomical areas to obtain as many controlled responses as possible. Reduce the TMS intensity in steps of 2%to 5%of the maximum stimulator output if the mapping induces pain or discomfort. Stop the measurement if the induced pain or discomfort is not tolerated by the subject.

When no naming error occurs, terminate the stimulation as demonstrated and change stimulation parameters. Decrease the IPI in steps of 200 milliseconds from the default value. Collaborate with an expert who should optimally be present in the operating room and double check the evoked naming errors by observing the coil positioning and possible pain interference from the video recordings.

Classify the errors as anomia, semantic and phonological paraphasia, and performance errors. If a particular type of error repeats itself in the baseline video, do not consider it an error. If an object is named after the repetitive mode TMS train, consider this a delay or a no error.

Also, check for possible discomfort of the subject during the pulse delivery. If the subject cannot name a given object although the tongue, lips and jaws are moving, record a no response error. If unsure, control the performance of the neighboring stimulation site or the effect of the stimulation of the other hemisphere with the same image.

The different TMS-evoked naming errors in a healthy subject during the task at different PTIs of 180, 200, and 215 milliseconds are shown here. Most of the errors were evoked in the classical speech areas and along the path connecting the pre-supplementary motor area and broca's area. A comparison of the results between extraoperative direct cortical stimulation mapping and navigated repetitive TMS with a fixed PTI at 300 milliseconds in a patient with intractable epilepsy is presented here.

In the direct cortical stimulation mapping, the yellow spheres represent all the electrodes on the cortex. The sites of stimulation with two to five milliamps induced motor responses of the hand and mouth, naming arrest, and interrupting sentence repetition. The navigated repetitive TMS of speech cortical mapping induced anomias, semantic and phonological paraphasia, and hesitations.

The areas with highly reproducible and reliable error induction are circled. Relevant and normalized images, sufficient baseline, flexibility in changing the parameters, if not errors, and careful video analysis are critical in this procedure. MEG, FMRI, and diffusion-based MRI can personalize the procedure and increase the sensitivity and specificity of this protocol.

EEG will be useful in the future to localize functional relevant areas in real time. This technique changed the pre-surgical evaluation standards and allowed scientists in the cortical mapping field to study the link between cortical structural and functional connectivity with behavior during cognitive tasks.