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Objective To characterize the spatiotemporal dynamics of auditory and picture naming-related cortical activation in Japanese-speaking patients. Methods Ten patients were assigned auditory naming and picture naming tasks during extraoperative intracranial EEG recording in a tertiary epilepsy center. Time-frequency analysis determined at what electrode sites and at what time windows during each task the amplitude of high-gamma activity (65–95 Hz) was modulated. Results The superior-temporal gyrus on each hemisphere showed high-gamma augmentation during sentence listening, whereas the left middle-temporal and inferior-frontal gyri showed high-gamma augmentation peaking around stimulus offset. Auditory naming-specific high-gamma augmentation was noted in the bilateral superior-temporal gyri as well as left frontal-parietal-temporal perisylvian network regions, whereas picture naming-specific augmentation was noted in the occipital-fusiform regions, bilaterally. The inferior pre- and postcentral gyri on each hemisphere showed modality-common high-gamma augmentation time-locked to overt responses. Conclusions The spatiotemporal dynamics of auditory and picture naming-related high-gamma augmentation in Japanese-speaking patients were qualitatively similar to those previously reported in studies of English-speaking patients. Significance The cortical dynamics for auditory sentence recognition are at least partly shared by cohorts speaking two distinct languages. Multicenter studies regarding the clinical utility of high-gamma language mapping across Eastern and Western hemispheres may be feasible.

A number of investigators have reported that event-related augmentation of high-gamma activity at 70–110 Hz on electrocorticography (ECoG) can localize functionally-important brain regions in children and adults who undergo epilepsy surgery. The advantages of ECoG-based language mapping over the gold-standard stimulation include: (i) lack of stimulation-induced seizures, (ii) better sensitivity of localization of language areas in young children, and (iii) shorter patient participant time. Despite its potential utility, ECoG-based language mapping is far less commonly practiced than stimulation mapping. Here, we have provided video presentations to explain, point-by-point, our own hardware setting and time–frequency analysis procedures. We also have provided standardized auditory stimuli, in multiple languages, ready to be used for ECoG-based language mapping. Finally, we discussed the technical aspects of ECoG-based mapping, including its pitfalls, to facilitate appropriate interpretation of the data.

Objective Intra-stimulation discharges (IDs) can occur during language mapping, are largely unrecognized, and may precede the occurrence of after-discharges (ADs) and seizures. This study aimed to identify predictors of ID occurrence and determine whether IDs increase the probability of triggered ADs. Methods A total of 332 stimulation events performed during language mapping were analyzed in 3 patients who underwent intracranial EEG recordings during evaluations for epilepsy surgery. IDs were identified in 76 stimulation events. The relationships between IDs and the stimulus current intensity, stimulation duration, and proximity to regions of abnormal cortical excitability [characterized by the presence of baseline epileptiform discharges (BEDs)] were determined using regression analysis. Results The presence of BEDs in close proximity to stimulation, an increase in stimulus intensity by 1 mA, and an increase in stimulation duration by 1 s independently increased the odds of triggering IDs by 7.40, 1.37, and 1.39 times, respectively. All IDs were triggered during stimulations in the temporal lobe. The occurrence of IDs increased the odds of triggering ADs 5-fold. Conclusions Longer stimulations, higher currents, and the presence of BEDs at the stimulation site increase the probability of ID occurrence, which in turn increases the probability of triggering ADs. Significance Attention to IDs may improve the safety and precision of neurophysiologic mapping.

Objective This article explores the feasibility of a novel repetitive navigated transcranial magnetic stimulation (rnTMS) system and compares language mapping results obtained by rnTMS in healthy volunteers and brain tumor patients. Methods Fifteen right-handed healthy volunteers and 50 right-handed consecutive patients with left-sided gliomas were examined with a picture-naming task combined with time-locked rnTMS (5–10 Hz and 80–120% resting motor threshold) applied over both hemispheres. Induced errors were classified into four psycholinguistic types and assigned to their respective cortical areas according to the coil position during stimulation. Results In healthy volunteers, language disturbances were almost exclusively induced in the left hemisphere. In patients errors were more frequent and induced at a comparative rate over both hemispheres. Predominantly dysarthric errors were induced in volunteers, whereas semantic errors were most frequent in the patient group. Conclusion The right hemisphere’s increased sensitivity to rnTMS suggests reorganization in language representation in brain tumor patients. Significance rnTMS is a novel technology for exploring cortical language representation. This study proves the feasibility and safety of rnTMS in patients with brain tumor.

We determined the utility of electrocorticography (ECoG) and stimulation for detecting language-related sites in patients with left-hemispheric language-dominance on Wada test.We studied 13 epileptic patients who underwent language mapping using event-related gamma-oscillations on ECoG and stimulation via subdural electrodes. Sites showing significant gamma-augmentation during an auditory-naming task were defined as language-related ECoG sites. Sites at which stimulation resulted in auditory perceptual changes, failure to verbalize a correct answer, or sensorimotor symptoms involving the mouth were defined as language-related stimulation sites. We determined how frequently these methods revealed language-related sites in the superior-temporal, inferior-frontal, dorsolateral-premotor, and inferior-Rolandic regions.Language-related sites in the superior-temporal and inferior-frontal gyri were detected by ECoG more frequently than stimulation (p0.05), while those in the dorsolateral-premotor and inferior-Rolandic regions were detected by both methods equally. Stimulation of language-related ECoG sites, compared to the others, more frequently elicited language symptoms (p0.00001). One patient developed dysphasia requiring in-patient speech therapy following resection of the dorsolateral-premotor and inferior-Rolandic regions containing language-related ECoG sites not otherwise detected by stimulation.Language-related gamma-oscillations may serve as an alternative biomarker of underlying language function in patients with left-hemispheric language-dominance.Measurement of language-related gamma-oscillations is warranted in presurgical evaluation of epileptic patients.

Introduction The resection of left-sided perisylvian brain lesions harbors the risk of postoperative aphasia. Because it is known that language function can shift between hemispheres in brain tumor patients, the preoperative knowledge of the patient’s language dominance could be helpful. Objective To investigate the correlation of hemispheric language dominance as measured by repetitive navigated transcranial magnetic stimulation (rTMS) and surgery-related deficits of language function. Patients & methods We pooled the bicentric language mapping data of 80 patients undergoing the resection of left-sided perisylvian brain lesions in our two university neurosurgical departments. We calculated error rates (ERs; ER = errors per stimulations) for both hemispheres and defined the hemispheric dominance ratio (HDR) as the quotient of the left- and right-sided ER (HDR > 1 = left dominant; HDR 1 = right dominant). The course of the patient’s language function was evaluated and correlated with the preoperative HDR. Result Only three of 80 patients (4%) presented with permanent surgery-related aphasia and 24 patients (30%) with transient surgery-related aphasia. The mean HDR (±standard deviation) of patients with new aphasia after five days was significantly higher (1.68 ± 1.07) than the HDR of patients with no new language deficit (1.37 ± 1.08) (p = 0.0482). With a predefined cut-off value of 0.5 for HDR, we achieved a sensitivity for predicting new aphasia of 100%. Conclusion A higher preoperative HDR significantly correlates with an increased risk for transient aphasia. Moreover, the intensive preoperative workup in this study led to a considerably low rate of permanent aphasia.

Introduction The resection of left-sided perisylvian brain lesions harbors the risk of postoperative language impairment. Therefore the individual patient’s language distribution is investigated by intraoperative direct cortical stimulation (DCS) during awake surgery. Yet, not all patients qualify for awake surgery. Non-invasive language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) has frequently shown a high correlation in comparison with the results of DCS language mapping in terms of language-negative brain regions. Objective To analyze the oncological and functional outcome of patients who underwent left-sided perisylvian resection of brain lesions purely based on rTMS language mapping. Patients & methods Four patients with left-sided perisylvian brain lesions (2 gliomas WHO III, 1 glioblastoma, 1 cavernous angioma) underwent rTMS language mapping prior to surgery. Data from rTMS language mapping and rTMS-based diffusion tensor imaging fiber tracking (DTI-FT) were transferred to the intraoperative neuronavigation system. Preoperatively, 5 days after surgery (=POD5), and 3 months after surgery (=POM3) clinical follow-up examinations were performed. Results No patient suffered from a new surgery-related aphasia at POM3. Three patients underwent complete resection immediately, while one patient required a second rTMS-based resection some days later to achieve the final, complete resection. Conclusion The present study shows for the first time the feasibility of successfully resecting language-eloquent brain lesions purely based on the results of negative language maps provided by rTMS language mapping and rTMS-based DTI-FT. In very select cases this technique can provide a rescue strategy with an optimal functional and oncological outcome when awake surgery is not feasible.

Introduction Functional magnetic resonance imaging (fMRI) is considered to be the standard method regarding non-invasive language mapping. However, repetitive navigated transcranial magnetic stimulation (rTMS) gains increasing importance with respect to that purpose. However, comparisons between both methods are sparse. Objective To compare the results of rTMS and fMRI language mapping in healthy volunteers. Patients & methods We performed fMRI and rTMS language mapping of the left hemisphere in 40 healthy, right-handed subjects in combination with the tasks that are most commonly used in the neurosurgical context (fMRI: word-generation = WGEN task; rTMS: object-naming = ON task). Different rTMS error rate thresholds (ERTs) were calculated, and Cohen’s kappa coefficient and the cortical parcellation system (CPS) were used for systematic comparison of the two techniques. Results Overall, mean kappa coefficients were low, revealing no distinct agreement. We found the highest agreement for both techniques when using the 2-out-of-3 rule (CPS region defined as language-positive in terms of rTMS if at least 2 out of 3 stimulations led to a naming error). However, kappa for this threshold was only 0.24, indicating fair agreement. Conclusions Regarding the comparison of fMRI and rTMS, language mapping results seem to differ in a wide range, at least when the tasks of the present trials are used. Since it is not possible to verify the present results via direct cortical stimulation (DCS) as the gold standard method, we must be careful to call one of the two techniques the true one. However, this study yields valuable results regarding the comparison of these frequently used mapping techniques for the most common language tasks applied in the neurosurgical routine.

Objective Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is in-creasingly used and already replaces functional magnetic resonance imaging (fMRI) in some institutions for preoperative mapping of neurosurgical patients. However, some factors affect the concordance of both methods with the gold standard direct cortical stimulation (DCS). We therefore analyze the impairment of rTMS and fMRI by intraparenchymal lesions as compared to the results of DCS during awake surgery. Methods We performed language mapping in 27 patients with left-sided perisylvian lesions by DCS, rTMS, and fMRI using an object-naming task, and assigned the obtained language eloquent sites of each method to Corina’s cortical parcellation system (CPS). Subsequently, we calculated the receiver operating characteristics for rTMS and fMRI compared to DCS, and analyzed different subgroups with (W) and with-out (WO) lesion in the mapped areas. Results Within the W subgroup we revealed an overall sensitivity of 100% (WO: 100%), a specificity of 8% (WO: 5%), a PPV of 34% (WO: 53%), and a NPV of 100% (WO: 100%) for the comparison of rTMS with DCS. For the comparison of fMRI with DCS within the W subgroup we obtained an overall sensitivity of 32% (WO: 62%), a specificity of 88% (WO: 60%), a PPV of 56% (WO: 62%), and a NPV of 73% (WO: 60%). Conclusion With this study we were able to show that rTMS is less affected by a brain lesion than fMRI, particularly when performing mapping of language-negative cortical regions based on sensitivity and NPV. With this in mind, rTMS could be useful for the language mapping assessment prior to the gold standard DCS.

Objective Various studies already explored cortical language function. However, language organization models and time course patterns are still derived from meta-analyses of numerous single publications, which only investigated scattered cortical regions. Yet, there is no systematic investigation on the distinct role and time course of the perisylvian cortex in language processing. Methods Ten right-handed volunteers (7 females & 3 males, mean age 27.2 ± 2.3 years) underwent rTMS language mapping of 12 predefined, left-hemispheric cortical regions known to be involved in language function. During investigation of each subject, rTMS pulses were applied with different picture-to-trigger intervals (PTIs) (0 ms, 100 ms, 200 ms, 300 ms, 400 ms, and 500 ms) in combination with an object naming task. Naming errors elicited by rTMS were categorized into six different error types (no-response error, performance error, hesitation, neologism, semantic error, and phonological error), and error rates (= number of errors/number of stimulations) and ratios (= number of errors of one category/total number of errors) for each category were calculated. Then, a predominant error type was defined, which represents the category with the highest error ratio per cortical region. Results The distribution of rTMS-induced naming errors changed according to the time point of naming disruption by varying PTIs: Immediate rTMS onset (PTI = 0 ms) led to a widespread cortical distribution of no responses, whereas performance and hesitation errors increased with PTIs, reaching their peak at 400 ms (performance errors) and 300 ms (hesitations). Conclusion In general, we were able to provide a time course of language processing by rTMS. Furthermore, the present study showed that the occurrence of different naming errors is significantly linked to the onset time of rTMS, and the time points of language subfunctions could be demonstrated.

Introduction Maximizing the extent of resection whilst preserving important brain functions is a major goal in the surgical treatment of brain tumours. For primary motor functions, the presurgical diagnostic techniques such as functional MRI (fMRI) and navigated transcranial magnetic stimulation (TMS) have improved a lot over the last decades and are extremely useful for preoperative risk evaluation and planning of the surgical approach. By contrast, presurgical mapping techniques for language-relevant areas are regarded poorly reliable (fMRI) and/or rather unspecific (repetitive TMS, rTMS). Methods We investigated the retest reliability of neuronavigated rTMS for speech/language mapping in 11 right-handed healthy volunteers in 3 consecutive sessions, spaced by 2–5 (short term) and 21–40 (long term) days. Navigated 10 Hz rTMS (Nexstim eXimia 4.2) was applied over the dominant hemisphere after determination of the individual inhibition threshold over the primary motor representation of the face/tongue. The bursts were triggered to picture presentation (naming task) without delay (picture-to-trigger interval = 0). Errors were categorised as follows: arrest, delay, anomia, dysarthria, semantic and phonematic paraphasia. Results As shown in Table 1 , a good feasibility in terms of the evocation of errors was observed. Per session, speech delays occurred most frequently (9.2 ± 2.1), followed by dysarthria (5.1 ± 2.4) and speech arrests (3.8 ± 1.8) whilst paraphasias were rather rare. There was a high variability in the distribution and the frequency of speech errors between the subjects. The reliability of the error frequency was rather good regarding long-term comparisons (Cohen’s weighted Kappa k = 0.41 [session 1–3]/k = 0.42 [session 2–3]) and still fair for the short-term (k = 0.29 [session 1–2]). Analyses of the spatial reliability of error representation are ongoing. Conclusions Presurgical speech/language mapping by neuronavigated rTMS is a promising tool to improve the risk evaluation and the planning of the surgical approach. In this preclinical study a rather satisfactory retest reliability of rTMS mapping at 10 Hz could be shown. However, since the method is still young, optimisation of the stimulation protocol and further intraoperative validation in clinical trials are required.

Objective Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is used for resection planning in patients suffering from brain lesions within regions known to be involved in language function. Yet, we also need data that show whether preoperative rTMS for language mapping also has an impact on the patients' clinical course and functional outcomes as it was proved for motor mapping. Methods We enrolled 25 patients with language eloquently located brain lesions undergoing preoperative rTMS language mapping (GROUP 1, 2011–2013) with mapping results not being available for the surgeon, and matched these patients with 25 subjects who also underwent preoperative rTMS (GROUP 2, 2013–2014), but mapping results were taken into account during awake mapping and tumor resection via implementation into the neuronavigation system. In addition, cortical language maps were generated by analyzing preoperative rTMS data. Results Mean craniotomy sizes were significantly smaller in patients of GROUP 2 (GROUP 1 vs. GROUP 2: 50.1±16.8cm 2 vs. 41.6±10.4cm 2 , p =0.0373), and postoperative language deficits were found significantly more often in patients of GROUP 1 ( p =0.0153), although preoperative language status did not differ between groups ( p =0.7576). Additionally, there was a trend towards less unexpected tumor residuals (GROUP 1 vs. GROUP 2: 32.0% vs. 16.0%, p =0.1853), shorter surgery duration (240.3±53.2min vs. 215.5±48.5min, p =0.0914), and higher postoperative KPS scores (80 vs. 90, p =0.2102) in GROUP 2 patients. Conclusion In general, the clinical course and functional outcomes of patients suffering from brain tumors might be improved by preoperative rTMS language mapping. Furthermore, reliable and precise language maps can be generated by rTMS in brain tumor patients, and this approach has once again proven to be safe, effective, and well-tolerable for the individual subject. However, more patients have to be enrolled for more definite data.