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T he resection of tumors within or adjacent to language-eloquent brain regions is still a neurosurgical quest, and a profound presurgical workup is crucial to achieving the best functional and oncological result. 6,71 Today, the most precise way to localize individual language-eloquent regions is direct cortical stimulation (DCS) during awake craniotomy. 9,12,26,44,45,54,62,65,74 Using only DCS, however, we cannot provide the longitudinal abbreviatioNs BOLD = blood oxygen level-dependent; CPS = cortical parcellation system; DCS direct cortical stimulation; ER = error rate; ERT error rate threshold; fMRI = functional MRI; IPI = interpicture interval; NPV = negative predictive value; nTMS navigated TMS; PPV = positive predictive value; PTI = picture-to-trigger interval; RMT = resting motor threshold; ROC = receiver operating characteristic; rTMS repetitive navigated TMS; TMS = transcranial magnetic stimulation. 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...

Navigated transcranial magnetic stimulation (nTMS) gains increasing importance in presurgical language mapping. Although bipolar direct cortical stimulation (DCS) is regarded as the gold standard for intraoperative mapping of language-related areas, it cannot be used to map the healthy human brain due to its invasive character. Therefore, the present study employed a non-invasive virtual-lesion modality to provide a causality-confirmed cortical language map of the healthy human brain by repetitive nTMS (rTMS) with functional specifications beyond language-positive/language-negative distinction. Fifty right-handed healthy volunteers underwent rTMS language mapping of the left hemisphere combined with an object-naming task. The induced errors were categorized and frequency maps were calculated. Moreover, a principal component analysis (PCA) was performed on the basis of language-positive cortical regions for each error category. The left hemisphere was stimulated at 258-789 sites (median: 361.5 sites), and 12-241 naming errors (median: 72.5 errors) were observed. In male subjects, a total number of 2091 language errors were elicited by 9579 stimulation trains, which is equal to an error rate of 21.8 %. Within females, 10,238 stimulation trains elicited 2032 language errors (19.8 %). PCA revealed that the inferior parietal lobe (IPL) and middle frontal gyrus (MFG) were causally involved in object naming as a semantic center and an executive control center. For the first time, this study provides causality-based data and a model that approximates the distribution of language-related cortical areas grouped for different functional aspects of single-word production processes by PCA.

Since transcranial magnetic stimulation (TMS) was introduced for stimulating the human motor cortex by Barker et al. in 1985, the method has become more sophisticated and was extensively refined.1 PascualLeone and colleagues introduced the term "virtual lesion" and were already in 1991 able to induce speech arrests and counting errors by the use of rapid-rate TMS. 35,36 In the late 1990s and early 2000s, a combination of TMS with optically tracked stereotactic navigation systems was established, whereby it was possible to visualize the stimulation sites via the 3D reconstructed MRI data of the patient's brain. 31,37 Thus, the door to the operating theater was opened since the recorded and analyzed stimulation sites could be used for presurgical planning and data could be abbreviatioNs BOLD = blood-oxygen-level dependent; CPS = cortical parcellation system; DCS = direct cortical stimulation; DTI-FT = diffusion tensor imaging fiber tracking; fMRI = functional MRI; NPV = negative predictive value; PPV = positive predictive value; PTI = picture-to-trigger interval; RMT = resting motor threshold; ROC = receiver operating characteristic; rTMS = repetitive navigated TMS; TMS = 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.

ObjectivesRecent repetitive TMS (rTMS) mapping protocols for language mapping revealed deficits of this method, mainly in posterior brain regions. Therefore this study analyzed the impact of different language tasks on the localization of language-positive brain regions and compared their effectiveness, especially with regard to posterior brain regions.MethodsNineteen healthy, right-handed subjects performed object naming, pseudoword reading, verb generation, and action naming during rTMS language mapping of the left hemisphere. Synchronically, 5 Hz/10 pulses were applied with a 0 ms delayResultsThe object naming task evoked the highest error rate (14%), followed by verb generation (13%) and action naming (11%). The latter revealed more errors in posterior than in anterior areas. Pseudoword reading barely generated errors, except for phonological paraphasias.ConclusionsIn general, among the evaluated language tasks, object naming is the most discriminative task to detect language-positive regions via rTMS. However, other tasks might be used for more specific questions.

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.

BackgroundAlthough language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) gains importance in neuropsychological research and clinical utility, neuroscientists still use different mapping protocols including different stimulation frequencies. To refine the existing language protocol, we tested two different repetition rates of 5 Hz/10 pulses and 7 Hz/10 pulses with a 0 ms delay in 19 healthy subjects. We furthermore investigated differences between both frequencies in case of performance of four different language tasks: object naming, pseudoword reading, verb generation, and action naming.ResultsEven the small variance in frequencies revealed statistically significant differences concerning the number and type of language errors. Stimulation with 5 Hz evoked a higher number of all occurred language errors in all language tasks (error rate object naming 14% (5 Hz) vs. 12% (7 Hz); pseudoword reading 4% (5 Hz) vs. 3% (7 Hz); verb generation 13% (5 Hz) vs. 11% (7 Hz); action naming 11% (5 Hz) vs. 9% (7 Hz)), whereas 7 Hz evoked specifically more total speech arrests.ConclusionThese findings suggest that the stimulation frequency has to be adapted to the aim of the rTMS language investigation.