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Neal Conway, Noémie Wildschuetz, Tobias Moser, Lucia Bulubas, Nico Sollmann, Noriko Tanigawa, Bernhard Meyer and Sandro M. Krieg

OBJECTIVE

The goal of this study was to obtain a better understanding of the mechanisms underlying cerebral plasticity. Coupled with noninvasive detection of its occurrence, such an understanding has huge potential to improve glioma therapy. The authors aimed to demonstrate the frequency of plastic reshaping, find clues to the patterns behind it, and prove that it can be recognized noninvasively using navigated transcranial magnetic stimulation (nTMS).

METHODS

The authors used nTMS to map cortical motor representation in 22 patients with gliomas affecting the precentral gyrus, preoperatively and 3–42 months postoperatively. Location changes of the primary motor area, defined as hotspots and map centers of gravity, were measured.

RESULTS

Spatial normalization and analysis of hotspots showed an average shift of 5.1 ± 0.9 mm (mean ± SEM) on the mediolateral axis, and 10.7 ± 1.6 mm on the anteroposterior axis. Map centers of gravity were found to have shifted by 4.6 ± 0.8 mm on the mediolateral, and 8.7 ± 1.5 mm on the anteroposterior axis. Motor-eloquent points tended to shift toward the tumor by 4.5 ± 3.6 mm if the lesion was anterior to the rolandic region and by 2.6 ± 3.3 mm if it was located posterior to the rolandic region. Overall, 9 of 16 (56%) patients with high-grade glioma and 3 of 6 (50%) patients with low-grade glioma showed a functional shift > 10 mm at the cortical level.

CONCLUSIONS

Despite the small size of this series, analysis of these data showed that cortical functional reorganization occurs quite frequently. Moreover, nTMS was shown to detect such plastic reorganization noninvasively.

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Sebastian Ille, Nico Sollmann, Theresa Hauck, Stefanie Maurer, Noriko Tanigawa, Thomas Obermueller, Chiara Negwer, Doris Droese, Claus Zimmer, Bernhard Meyer, Florian Ringel and Sandro M. Krieg

OBJECT

Repetitive navigated transcranial magnetic stimulation (rTMS) is now increasingly used for preoperative language mapping in patients with lesions in language-related areas of the brain. Yet its correlation with intraoperative direct cortical stimulation (DCS) has to be improved. To increase rTMS's specificity and positive predictive value, the authors aim to provide thresholds for rTMS's positive language areas. Moreover, they propose a protocol for combining rTMS with functional MRI (fMRI) to combine the strength of both methods.

METHODS

The authors performed multimodal language mapping in 35 patients with left-sided perisylvian lesions by using rTMS, fMRI, and DCS. The rTMS mappings were conducted with a picture-to-trigger interval (PTI, time between stimulus presentation and stimulation onset) of either 0 or 300 msec. The error rates (ERs; that is, the number of errors per number of stimulations) were calculated for each region of the cortical parcellation system (CPS). Subsequently, the rTMS mappings were analyzed through different error rate thresholds (ERT; that is, the ER at which a CPS region was defined as language positive in terms of rTMS), and the 2-out-of-3 rule (a stimulation site was defined as language positive in terms of rTMS if at least 2 out of 3 stimulations caused an error). As a second step, the authors combined the results of fMRI and rTMS in a predefined protocol of combined noninvasive mapping. To validate this noninvasive protocol, they correlated its results to DCS during awake surgery.

RESULTS

The analysis by different rTMS ERTs obtained the highest correlation regarding sensitivity and a low rate of false positives for the ERTs of 15%, 20%, 25%, and the 2-out-of-3 rule. However, when comparing the combined fMRI and rTMS results with DCS, the authors observed an overall specificity of 83%, a positive predictive value of 51%, a sensitivity of 98%, and a negative predictive value of 95%.

CONCLUSIONS

In comparison with fMRI, rTMS is a more sensitive but less specific tool for preoperative language mapping than DCS. Moreover, rTMS is most reliable when using ERTs of 15%, 20%, 25%, or the 2-out-of-3 rule and a PTI of 0 msec. Furthermore, the combination of fMRI and rTMS leads to a higher correlation to DCS than both techniques alone, and the presented protocols for combined noninvasive language mapping might play a supportive role in the language-mapping assessment prior to the gold-standard intraoperative DCS.

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Sebastian Ille, Nico Sollmann, Theresa Hauck, Stefanie Maurer, Noriko Tanigawa, Thomas Obermueller, Chiara Negwer, Doris Droese, Tobias Boeckh-Behrens, Bernhard Meyer, Florian Ringel and Sandro M. Krieg

OBJECT

Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is increasingly used and has already replaced functional MRI (fMRI) in some institutions for preoperative mapping of neurosurgical patients. Yet some factors affect the concordance of both methods with direct cortical stimulation (DCS), most likely by lesions affecting cortical oxygenation levels. Therefore, the impairment of the accuracy of rTMS and fMRI was analyzed and compared with DCS during awake surgery in patients with intraparenchymal lesions.

METHODS

Language mapping was performed by DCS, rTMS, and fMRI using an object-naming task in 27 patients with left-sided perisylvian lesions, and the induced language errors of each method were assigned to the cortical parcellation system. Subsequently, the receiver operating characteristics were calculated for rTMS and fMRI and compared with DCS as ground truth for regions with (w/) and without (w/o) the lesion in the mapped regions.

RESULTS

The w/ subgroup revealed a sensitivity of 100% (w/o 100%), a specificity of 8% (w/o 5%), a positive predictive value of 34% (w/o: 53%), and a negative predictive value (NPV) of 100% (w/o: 100%) for the comparison of rTMS versus DCS. Findings for the comparison of fMRI versus DCS within the w/ subgroup revealed a sensitivity of 32% (w/o: 62%), a specificity of 88% (w/o: 60%), a positive predictive value of 56% (w/o: 62%), and a NPV of 73% (w/o: 60%).

CONCLUSIONS

Although strengths and weaknesses exist for both rTMS and fMRI, the results show that rTMS is less affected by a brain lesion than fMRI, especially when performing mapping of language-negative cortical regions based on sensitivity and NPV.