A Standardized Protocol for Functional Motor Mapping Using Navigated Transcranial Magnetic Stimulation

We present a standardized protocol for motor mapping and corticospinal tract assessment using navigated TMS combined with DTI suitable for neurosurgical planning and neuroplasticity research. While intraoperative direct electrical stimulation is the gold standard for motor mapping, existing preoperative methods are limited. Improved preoperative motor mapping methods are required to help neurosurgeons improve their surgical planning and better assess surgical risks.

This protocol uses navigated TMS for accurate motor pathway mapping and improved surgical planning. To begin, import high-resolution anatomical brain images of the subject into the neuronavigation system to generate a three-dimensional brain reconstruction. Mark the key anatomical points on the magnetic resonance imaging within the neuronavigation software by identifying the nasion, right ear, and left ear.

Now, position the subject on a comfortable armchair with a slight recline to reduce back tension. Adjust the headrest to support the head and neck at the inion. Place the head tracker on the subject's forehead.

Using the digitizing pen, coregister the key anatomical points on the subject with the imported image in the neuronavigation software and refine the registration by digitizing additional scalp points for scalp surface matching. Validate the coregistration, ensuring a coregistration error below three millimeters. Next, give the subject a pair of earplugs and wear protective earmuffs during stimulation.

Then prepare the skin over the target muscle by gently scraping it using alcohol pads and subsequently attach surface electrodes. Place surface electrodes on the muscles of interest using a belly-tendon montage and the ground electrode on a neutral site. Connect all electrodes to the electromyography amplifier.

Start electromyography acquisition and verify that the muscles are at rest. On the rendered brain volume within the neuronavigation software, adjust the peeling depth to between 15 and 25 millimeters from the scalp to optimally visualize the cortical anatomy based on individual case characteristics, then start the stimulator unit. Position the stimulation coil tangentially to the scalp and stabilize it using one hand on the handle and the other on the coil surface to maintain firm contact during repositioning.

Stimulate at an intensity sufficient to elicit motor revoked potentials within the amplitude range of 100 to 500 microvolts. Now, adjust the coil orientation based on the limb being mapped. For the upper limb and the face, maintain the coil perpendicular to the central sulcus to ensure a posterior-to-anterior induced current.

For the lower limb, orient the coil perpendicular to the sagittal midline to generate a mid-to-lateral current direction. Perform stimulations across the target region. Space the stimulation points one to two millimeters apart and sample three parallel lines along the gyrus.

Space each stimulation by at least 1.5 seconds. Stop the course mapping once 20 to 30 motor evoked potentials per muscle have been recorded and review all motor evoked potentials. Next, display the recordings using a normalized color scale to identify the hotspot for each muscle, defined as the stimulation point that evokes the largest motor evoked potential amplitude.

Locate the area containing the highest amplitude responses and select the single response with the largest amplitude within that region. For each muscle, select the hotspot to determine the resting motor threshold to store the coil's position and orientation for consistent use during the threshold measurement and determine the resting motor threshold for each muscle. Ensure that the subject remains fully relaxed without any involuntary muscle contractions.

For each muscle, perform stimulation at 105%to 110%of its resting motor threshold. Using the same coil orientation as during course mapping, reduce the spacing between stimulation points for higher resolution. Delineate functional motor maps as cortical areas, where navigated transcranial magnetic stimulation generates motor evoked potentials of 50 microvolts or higher.

Perform stimulation until the motor maps are bordered by one or two consecutive lines of negative sites that fail to elicit motor evoked potentials. Ensure the motor maps are elliptic, with few negative sites inside. For any negative stimulation points within the motor map, perform additional stimulations at different times to account for transient changes in motor cortex excitability.

Open the motor evoked potential review panel or signal viewer in the neuronavigation software. Inspect each recorded motor evoked potential to correct amplitude and latency and adjust markers if needed. Exclude artifactual or abnormal stimulation points from the dataset and display the motor map for each muscle in a binary format.

Export the positive stimulation points at 15, 20, and 25-millimeter depths in binarized DICOM format. Use these files for fiber tracking, employing the positive stimulation points as seed points for corticospinal tract reconstruction. For analysis of motor mapping, import the DICOM files of the motor maps into an image analysis software compatible with neurosurgical neuronavigation for brain tumor removal.

Register the anatomical T1-weighted image with the motor map DICOMs and diffusion-weighted imaging files. Generate objects from the motor map DICOMs and expand them by one to two millimeters to enhance sensitivity. Crop the motor maps to exclude the ears and nasion in order to avoid incorrect fiber reconstruction during tractography.

Manually draw an ending region of interest at the inferior pontine level on the same side as the mapped hemisphere. Perform fiber tracking using the motor map regions of interest as seed points and the pontine region of interest as the endpoint. Select a suitable tractography algorithm, such as deterministic streamlined tracking or probabilistic tractography, and adjust tracking parameters according to the specific case.

Finally, segment the brain tumor and create a corresponding object within the analysis software. Display the corticospinal tract either separated by limb part using different colors or as a unified tract from the entire motor mapping. The resting motor threshold was determined at the hotspot of the first interosseous dorsalis muscle identified through course mapping in a healthy subject, and the coil position and orientation were maintained at the same location during the procedure using a neuronavigation target.

Motor mapping of a healthy subject revealed cortical representations for the left lower limb, upper limb, and face, with positive stimulation sites color coded by motor evoked potential amplitude and negative sites shown in gray. Motor cortical mapping and reconstruction of the corticospinal tracts were performed in a patient with brain metastasis from lung cancer involving the premotor gyrus with an upper limb motor deficit. By combining neuronavigation with the subject's anatomical brain, this NTMS protocol provides precise identification and delineation of motor eloquent cortical regions in under 19 minutes.

Careful selection of stimulation intensity is critical, as it affect motor evoked potential determination and motor map interpretation. Net result level provide conservative map approximating direct electrical stimulation. This technique was first developed to provide clinically useful functional information for surgical planning.

In addition, we know now that this technique is able to be applied for longitudinal assessment of motor plasticity in various neurological or psychiatric disorders.