Robot-assisted image-guided transcranial magnetic stimulation for somatotopic mapping of the motor cortex: a clinical pilot study

At the time of Ri-TMS, one of five patients required anticonvulsant medication because of a history of focal seizures. Medication of the other patients included dexamethasone and non-steroidal antiphlogistic therapy, which are not known to interfere with TMS. During the Ri-TMS, the patients were allowed to position and move their heads freely. Both hemispheres were examined, with the exception of one patient who developed a focal seizure and discontinued the mapping study. The stimulation intensity used for the mapping was selected between 40% and 45% (43 ± 2, mean ± SD) of maximum stimulator output (MSO). This corresponds well with the intensities other authors applied for the same task [24]. Per hemisphere, an average of 38 grid points (range 32–60) was examined (Table 1). Measurements were started at a grid point directly above the anatomical hand knob identified on the surface reconstruction of MRI and continued in all planar directions at a grid width of 8 mm until no MEP response could be elicited in the muscle group of interest (Fig. 1, panel H).

The areas of maximal MEP response by Ri-TMS and fMRI activation were projected as maps on the surface reconstructions from MRI for each individual (Fig. 2). In a healthy volunteer, Ri-TMS was performed for both hemispheres. The maps of the calculated maximal MEP response demonstrated a maximal MEP response of the m. abductor digiti minimi in an area corresponding to the “hand knob” of the precentral gyrus (Fig. 2a). The area of maximal MEP response of the m. abductor digiti minimi was similar for the left and right hemispheres and corresponded well to the expected anatomical region (Fig. 2a and b). Repeated measurements using de novo registration and de novo definition of a grid system for Ri-TMS demonstrated a high reproducibility with the MEP response of the m. abductor digiti minimi localizing to exactly the same anatomical site (Fig. 2a and c).

Simultaneous registration of the MEP response for m. brachioradialis, m. abductor pollicis brevis, and m. abductor digiti minimi demonstrated individual peak areas of maximal MEP response for the individual muscle groups, which corresponded to their expected somatotopic representation within the precentral gyrus (Fig. 3 a, b and c). fMRI using a “finger tapping” paradigm showed activation of larger areas of the precentral gyrus and parts of the postcentral gyrus. The areas of maximal MEP response for m. brachioradialis, m. abductor pollicis brevis, and m. abductor digiti minimi matched with the area of fMRI activation (Fig. 3d). In four of five patients with intracranial tumors near the motor cortex, Ri-TMS mapping of the effected hemisphere allowed identification of clearly distinct areas of maximal MEP response for the three muscles. In one patient (patient #2) with a large postcentral histologically confirmed glioblastoma, Ri-TMS mapping localized the maximal MEP response for all three muscles to a relatively large area of the precentral gyrus. However, the areas of maximal MEP response for each of the three muscles overlapped, which did not allow discrimination of the individual peak areas of MEP response for the individual muscles. In a case of a low-grade glioma (patient #5) involving the left central region and displacing the precentral gyrus rostrally, Ri-TMS mapping demonstrated highly circumscript areas of maximal MEP response for the m. brachioradialis, m. abductor pollicis brevis, and m. abductor digiti minimi, but the three peak areas localized to a small area of the distorted precentral gyrus (Fig. 4). In both of these cases, identification of distinct cortical motor areas for the three muscles was possible for the unaffected contralateral hemisphere (Table 1).

Using a “finger tapping” paradigm, fMRI for all individuals tested showed a large area of activation within the lateral precental gyrus and, to a varying extent, activation of the ipsilateral SMA, the contralateral precentral gyrus, some postcentral areas and bilateral cerebellar areas. When Ri-TMS mapping was compared to the corresponding fMRI studies, the areas of maximal MEP response for the three muscles localized within the “finger tapping”-activated areas by fMRI in four of five patients and the healthy volunteer (compare Table 1). For patient #2, a partial overlap of the area of maximal MEP response and fMRI was found.

Two of the five patients examined by Ri-TMS had previously undergone biopsy and did present for follow up examination only, the other three were scheduled for surgery and intraoperative ECS was performed during tumor resection in two of these (in the third case, the central region was not exposed during surgery). In two of these patients prior to surgery, the Ri-TMS spatial coordinates of the maximal MEP response were integrated into the neuronavigational device (VectorVision 2) to allow a reference for intraoperative acquisition of ECS data. Intraoperative direct electrical stimulation of the motor cortex successfully located areas of maximal MEP for different muscles in hand and forearm in both patients. Areas of maximal MEP response were registered using the neuronavigation (Fig. 5). Measurements of the cortical distance between the areas of peak MEP response to preoperative Ri-TCM and intraoperative ECS were performed. This analysis demonstrated distances between 5 and 26.3 mm. For the latter case, access to the precentral gyrus could only be obtained after removal of a large tumor and significant volume shifts had occurred (compare Table 1.).