Non-Invasive Modulation and Robotic Mapping of Motor Cortex in the Developing Brain

Our protocol involves using the first pediatric TMS robot in the world to map the motor cortex in healthy children and also in children who have had early brain injuries such as perinatal stroke. Protocol integrates MRI imaging with neuronavigation, which allows us to acquire maps with increased accuracy and precision, reduce mapping session times. It helps eliminate human error and it increases safety and tolerability for young patients.

Motor mapping is not yet used for diagnostic or prognostic purposes, however, it is a novel technique that measures how the brain changes and rewires after either damage to the brain has occurred or after an intervention. Similar techniques with different targets can be used for language area mapping. Language and motor mapping can be important for pre-surgical planning.

Begin by using the tabs in the neuronavigation software to reconstruct skin and full brain curvilinear. Select new, skin, and compute skin. Ensure the nose and top of the head are included.

Then, select new and full brain curvilinear. Enclose the green selection box outside of the brain, but inside of the skull. Select compute curvilinear.

Adjust the peel depth to 4.0 to 6.0 millimeters. Select configure landmarks. Place four landmarks at the tip of the nose, nasion, and the notches of both ears of the reconstructed skin.

Name the landmarks corresponding to their anatomy. Select the target’s tab to view the curvilinear brain. Select new and rectangular grid.

Place uniform 12 by 12 coordinate grids with seven millimeter spacing on the surface of the reconstructed brain over the handknob of the motor cortex. Next, use the target positioning tool on the right to optimize the grid positioning for rotation, tilt, and curvature. Convert the grid points into trajectories that will guide the robot to position the TMS coil.

Adjust the angle of the trajectory so they are 45 degrees to the longitudinal fissure or the brain. Use the snap tool to extrapolate and optimize the trajectories to the curvilinear brain. Finally, initialize and position the TMS robot arm and seat to welcome position and calibrate the force plate sensor using four sensor test.

Begin by escorting the participant into the testing room and having them fill out a safety questionnaire. Then, seat the participant in the robot chair and adjust the backrest and neck rest. Ensure their feet are supported.

Support the arms and hands with pillows during the mapping session. Clean the skin over the muscle of interest. Place silver silver chloride surface electrodes on both hands and forearms of the participant targeting four distal forelimb muscles.

The belly of the first dorsal interosseous, abductor pollicis brevis, abductor digiti minimi, and the wrist extensor. Connect the amplifier to a data collecting computer with compatible EMG software. Next, surface electrodes to the electromyography, or EMG, amplifier and a data acquisition system, making sure that the ground electrode is connected as well.

Co-register the four landmarks on the head of the participant using the landmark pointers and use the validation tab to ensure the participants head is properly registered. Then, select a grid point closest to the participant’s handknob. Select the align to target button to align the TMS coil held by the robot to this target location.

Select contact on. Monitor the contact quality using the contact force indicator and ensure the indicator is green or yellow. Instruct the participant not to move outside the scope of the robot arm.

Ensure the participant’s hand muscles are relaxed and remain still prior to contact. Select align and follow so the coil remains centered on the target if the participant moves. Use the TMS trigger button on the TMS machine to deliver five to 10 TMS pulses at an intensity between 40 to 60%maximum stimulator output.

Lastly, determine the grid point that gives the largest and most consistent motor evoked potential for the left or right FDI muscle. Determine the resting motor threshold as the lowest intensity that produces and MEP of at least 50 microvolts in the FDI muscle in five out of 10 stimulation. Begin by delivering four single pulse TMS pulses at an interstimulus of one second and intensity of 120%RMT at the grid point closes to the hotspot.

Then, repeat at the adjacent grid point. Continue sequentially in a linear fashion along responsive points until a non-responsive point is reached, which designates the first boarder region of the map. Then, continue mapping to establish the boarder points in all four directions of the rectangular grid.

Record all MEPs from all muscles using the EMG software for offline analysis. After three to four grid points, select contact off and give the participant a break until they feel ready to continue. Next, use a hard copy version of the same grids to track the stimulation order for further analysis.

Complete mapping using a robotic TMS. Finally, use a custom made coding script to generate 3D motor maps available by contacting the author. Calculate motor map area and volume using responsive trajectory sites.

Calculate center of gravity as weighted average of the motor representations of each coordinate location. These results indicated that tDCS and HD-tDCS improved the rate of learning over five days of training. The active intervention groups had larger improvements in daily average left hand PPT score at day four and five compared to sham.

This methodology has been replicated from a previous study and the data sets were combined. The replication data demonstrated similar results such that there was a significant increase in the rate of learning observed in the tDCS and HD-tDCS group compared to the sham group. Planning the procedure is as important as performing it.

Grids and trajectories should be carefully overlaid on an MRI. If using brain templates, multiple samples should be taken from the participants head. This procedure can be completed pre-and post-intervention to answer resulting motor map change.

Performing assessment following this procedure can indicate the relationship between motor map measures and function outcome. Using this protocol, researchers can learn how to generate motor maps accurately, timely, as well as safely in children using robotic TMS. Major challenge include guiding the robot and aligning it optimal its target areas.

The trajectories must be accurately predetermined. Practicing coil alignment with multiple combinations of tilt and rotation parameters helps optimize coil trajectory design. None of the instruments are hazardous.

It is important to constantly observe the robot while it is touching the participant’s head as the robot will react to any head movements.