*2.5. Statistics*

Statistical analysis was performed in GraphPad Prism (version 8.0.0, GraphPad Software, San Diego, CA, USA). Due to the lack of prior investigations in the literature, we were hesitant to assume any given data distribution. Therefore, we tested for statistically significant differences between CT- and MRI-based e-field maxima using the non-parametric Wilcoxon matched-pairs signed rank test. The level of statistical significance was defined as *p* < 0.05.

### **3. Results**

#### *3.1. Patients*

We performed motor mappings by nTMS in a group of 21 patients (6 females) with a range of diagnoses and etiologies (Table 2). Median age was 69 years (age range: 17–89 years). Seven patients were mapped under sedation via propofol (median dosage: 30 mcg/kg/min, dosage range: 15–80 mcg/kg/min). Nine patients underwent motor mapping of a hemisphere ipsilateral to hemicraniectomy. Five patients had ICP monitoring in place (two via drainage, three via cranial bolt). Average ICP in these cases was 15 ± 4 mmHg (median ICP: 17 mmHG, range ICP: 9–18 mmHg).


**Table 2.** Patient overview.

This table shows an overview over all patients included in this study. Abbreviations: subarachnoidal hemorrhage (SAH), subdural hemorrhage (SDH), internal carotid artery (ICA), traumatic brain injury (TBI), intraparenchymal hemorrhage (IPH).

#### *3.2. Imaging Testing Results*

The average difference of CT to MRI e-fields was −0.4 V/<sup>m</sup> ± 7.5 V/m (median difference: 0 V/m), and the maximum difference in e-fields between corresponding points was 18 V/m. In our statistical analysis of recorded e-field values, we found no statistically significant difference (mean CT e-field: <sup>52</sup> <sup>±</sup> 14 V/m vs. mean MRI e-field: 52 <sup>±</sup> 11 V/m; *<sup>p</sup>* <sup>=</sup> 0.6574).

#### *3.3. Mapping Results*

MEPs were successfully evoked in 18 patients. Average rMT (in percent of maximum stimulator output) was 63 ± 20% (median rMT: 68%, rMT range: 28–91%) for left hemisphere and 62 ± 22% (median rMT: 63%, rMT range: 31–100%) for right hemisphere. Within the sedated group of patients, MEPs were successfully evoked in 5 out of 7 patients, including the two cases with the highest observed sedation levels of 80 mcg/kg/min and 70 mcg/kg/min propofol, respectively. Excluding image preparation, time required per mapped hemisphere was approximately 90 min.

There were no adverse effects during or immediately after motor mapping. Conscious patients did not report the stimulation to be painful or uncomfortable. We observed no changes in continuously monitored autonomic parameters (O<sup>2</sup> saturation, blood pressure, heart frequency, ICP) attributable to stimulation. nTMS motor mapping did not prevent any other necessary procedure (e.g., neurochecks, application of medication, and suction) from being carried out. If necessary, the mapping was paused until the end of the procedure.

Intracranial access devices (e.g., subdural drainage and cranial bolt) interfered with motor mappings due to physical limitations imposed on coil placement. Cranial bolts specifically blocked access to sections of the respective hemisphere by taking up space. Motor mapping in these patients was, therefore, restricted to the hemisphere contralateral to the cranial bolt. ICP monitoring via drainages complicated but did not prohibit mappings of the ipsilateral cortex.

Additionally, we were able to demonstrate that nTMS navigation equipment interferes with pulse oximetry (Figure 2). This problem was solved by putting textiles over the probe, thereby blocking the interfering signal.

**Figure 2.** Interference of navigation equipment with pulse oximetry. This figure demonstrates the effect that the navigated transcranial magnetic stimulation (nTMS) navigational system imposes on pulse oximetry. The underlying mechanism is likely the infrared-spectrum based navigational camera creating interference with light used in pulse oximetry. The white arrow indicates the moment at which the camera was positioned for nTMS navigation. The red arrow indicates the moment at which a layer of textiles was put over the pulse oximetry probe.
