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Intraoperative functional mapping of tumor and peri-tumor tissue is a well-established technique for avoiding permanent neurologic deficits and maximizing extent of resection. Motor, language, and other cognitive domains may be assessed with intraoperative tasks. This article describes techniques used for motor and language mapping including awake mapping considerations in addition to less traditional intraoperative testing paradigms for cognition. It also discusses complications associated with mapping and insights into complication avoidance.

Purpose We studied the association between electrical stimulation mapping (ESM) with a visual naming task and post-operative neuropsychological outcomes after pediatric epilepsy surgery. Methods Children who underwent epilepsy surgery, having pre- and 1-year post-surgery neuropsychological evaluation (NPE) available, were included. NPE scores were transformed using principal components (PC) analysis. The relationship between post-surgical PC scores, adjusted for pre-surgery PC scores, and ESM was analyzed. Clinical variables influencing this relationship were also sought. Results One hundred and four children (89 patients >5 years-old, and 15 patients 3−5 years-old) were included. Among children >5 years-of-age, a significant effect of language ESM was observed on all 3 post-surgery PC scores adjusted for respective pre-surgery PC scores. Specifically, only 30 % patients who underwent language ESM had a decrease in PC1 scores ≥1-year after epilepsy surgery, compared to 68 % those who did not undergo language ESM (p = 0.001). Seizure outcomes, age at the time of surgery, predominant seizure type, and family history of epilepsy were other significant determinants of post-surgical PC scores including a change in PC scores from pre-surgery baseline. Combinations of pre-surgical variables were able to predict post-surgical PC scores with high specificity. In children aged 3−5 years, no significant effect of language ESM was seen on post-surgery PC scores adjusted for respective pre-surgery PC scores. Conclusions Speech/language ESM should be performed more widely in patients >5 years-of-age undergoing epilepsy surgery. Also, more efficient brain mapping techniques and language paradigms are needed for younger children.

Objective The aim of the present study was to compare localization of the language cortex using electrical cortical stimulation (ECS) and functional magnetic resonance imaging (fMRI) to establish the relevance of fMRI language mapping. Methods Language mapping with fMRI and functional ECS mapping were retrospectively compared in ten patients with refractory epilepsy who underwent fMRI language mapping and functional ECS mapping between June 2012 and April 2019. A shiritori task, a popular Japanese word chain game, was used for fMRI language mapping. Results BOLD signal activation was observed in the left inferior frontal gyrus (including the pars opecularis and the pars triangularis), and superior temporal gyrus, which is a language-related area, as well as in the left superior and middle frontal gyri, the intraparietal sulcus, and fusiform gyrus. These results were compared with ECS to elucidate the functional role of the activated areas during fMRI language tasks. These activated areas included language areas, negative motor areas, supplementary motor areas (SMAs), and non-functional areas. Conclusion The activated areas of fMRI language mapping include language-related areas, the negative motor area, and SMAs. These findings suggest the involvement of language and higher order motor networks in verbal expression.

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.

Highlights • Awake craniotomy for language mapping in children requires a specific perioperative strategy. • Extraoperative language cortical mapping using a grid electrode provides more optimal setting that reduces anxiety and improves compliance. • The utilization of video game familiar to the pediatric patient reduce anxiety and enhance cooperation during awake language cortical mapping., Intraoperative functional language mapping is vital to minimize the risks associated with surgical removal of the seizure onset zone in selected patients with epilepsy. In children, this method has been reported extraoperatively by the placement of invasive electrodes to map the language area and monitor epileptic activity. It is difficult from a technical standpoint to perform an awake craniotomy and language mapping in young children under 10 years of age. Here we report a 9-year-old boy suffering from drug-resistant non-lesional epilepsy who underwent extraoperative and intraoperative electrical stimulation with successful identification of Broca’s language area. Electrocorticography (ECOG) was applied intraoperatively in a continuous manner utilizing grid electrodes before the skin opening. We found that the use of visual digital video games facilitated extraoperative and intraoperative cortical mapping. Cortical language inhibition by electrical stimulation was elicited at an amplitude of 7 mA (100 μs single-phase duration and 50 Hz pulse width). Resection of the seizure onset zone was completed safely. The post-resection ECOG revealed the disappearance of epileptogenic electrographic discharges at the seizure onset contacts and at other involved contacts in the epileptogenic zone. After surgery, the child recovered well with no language deficits and remained seizure-free. The child remembered only the video game test that was performed intraoperatively. This report highlights safety strategies for awake language mapping in pediatrics and the importance of the perioperative use of a visual digital video game and continuous ECOG, in addition to the use of targeted language cortex stimulation to facilitate faster and safer intraoperative language mapping under awake conditions in this age group.

Objective To report a technique for endoscopic cystoventriculostomy guided by preoperative navigated transcranial magnetic stimulation (nTMS) and tractography in a patient with a large speech eloquent arachnoid cyst. Methods A 74-year old woman presented with a seizure and subsequent persistent anomic aphasia from a progressive left-sided parietal arachnoid cyst. An endoscopic cystoventriculostomy and endoscope-assisted ventricle catheter placement were performed. Surgery was guided by preoperative nTMS and tractography to avoid eloquent language, motor, and visual pathways. Results Preoperative nTMS motor and language mapping were used to guide tractography of motor and language white matter tracts. The ideal locations of entry point and cystoventriculostomy as well as trajectory for stent-placement were determined preoperatively with a pseudo-3-dimensional model visualizing eloquent language, motor, and visual cortical and subcortical information. The early postoperative course was uneventful. At her 3-month follow-up visit, her language impairments had completely recovered. Additionally, magnetic resonance imaging demonstrated complete collapse of the arachnoid cyst. Conclusion The combination of nTMS and tractography supports the identification of a safe trajectory for cystoventriculostomy in eloquent arachnoid cysts.

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.

Resting state functional MR imaging (rs-fMR imaging) has become an indispensable tool for examining brain function. The greatest opportunity to translate rs-fMR imaging from the research domain into clinical use is as a tool for examining intrinsic brain networks for preoperative planning. Many studies have demonstrated concordance of intrinsic motor networks from rs-fMR imaging data with task-fMR imaging and direct cortical stimulation. Earlier reports show concordance of language networks as well, although more recent studies with larger numbers of subjects demonstrate subject-level variability that needs to be further investigated and addressed before widespread implementation of rs-fMR imaging for preoperative planning.

Objective The value of preoperative repetitive transcranial magnetic stimulation (rTMS) language mapping for function preservation in surgery of speech-eloquent lesions under general anesthesia remains to be determined. Methods We prospectively enrolled 20 consecutive right-handed patients with a malignant, left-sided perisylvian language-eloquent brain tumor. All patients were subjected to surgical resection under general anesthesia guided by preoperative rTMS language mapping (rTMS group, 2014–2016). A matched-pair analysis with 20 patients who also underwent surgical resection under general anesthesia in the pre-rTMS era (pre-rTMS group, 2009–2013) was performed. Language performance status was ranked from grade 0 to grade 3 (none, mild, medium, severe). Results Rates of gross total resection, tumor residual, and complications were equal in both groups. Duration of surgery ( P = 0.039) and inpatient stay ( P = 0.001) were significantly shorter in the rTMS group. Preoperatively, 14 patients in the rTMS and 13 patients in the pre-rTMS group had language deficits ( P = 0.380). One week after surgery, 8/14 patients (57.1%) in the rTMS group but only 1/13 patients (7.7%) in the pre-rTMS group experienced improvement of language performance status ( P = 0.013). At 6 weeks follow-up, language performance status was significantly better in the rTMS group ( P = 0.048). However, at 3 months follow-up, the rTMS and pre-rTMS groups showed an equal language performance status. Conclusions Implementation of preoperative rTMS language mapping seems to provide a favorable early language outcome in patients undergoing surgical resection of language-eloquent lesions under general anesthesia.

Objective The objective of the study was to develop and clinically test a trial-free online-based language mapping method for localizing the eloquent cortex easily in epilepsy operation. Methods Nine patients with refractory epilepsy were included in this study according to the results of preoperative evaluation for their epileptogenic zones (EZs) located adjacent to the eloquent cortex. When patients were awakened up from general anesthesia during operation, the trial-free online-based language-mapping paradigm was performed. All positive points marked on the cortex in each test were labeled and superimposed together as the result of functional mapping for each patient. The eloquent cortex was mapped according to the results obtained both from the intraoperative trial-free task localization method and the traditional electrical cortical stimulation (ECS). Results All patients completed this paradigms twice within 10 min. Based on the results of mapping, the EZs were tried to fully resected on the premise of preserving the mapped eloquent cortex as much as possible. The postoperative follow-up showed the outcome of Engel I in six patients and Engel II in three patients, whereas only two patients had aphemia after surgery and recovered within one week and three months, respectively. Significance The intraoperative trial-free online-based language mapping method was primarily identified to be safe and effective. This novel method seems to be promising and worthy of improvement.

Development of a task-free method for presurgical mapping of language function is important for use in young or cognitively impaired patients. Resting state connectivity fMRI (RS-fMRI) is a task-free method that may be used to identify cognitive networks. We developed a voxelwise RS-fMRI metric, Functional Connectivity Hemispheric Contrast (FC-HC), to map the language network and determine language laterality through comparison of within-hemispheric language network connections (Integration) to cross-hemispheric connections (Segregation). For the first time, we demonstrated robustness and efficacy of a RS-fMRI metric to map language networks across five groups (total N = 243) that differed in MRI scanning parameters, fMRI scanning protocols, age, and development (typical vs pediatric epilepsy). The resting state FC-HC maps for the healthy pediatric and adult groups showed higher values in the left hemisphere, and had high agreement with standard task language fMRI; in contrast, the epilepsy patient group map was bilateral. FC-HC has strong but not perfect agreement with task fMRI and thus, may reflect related and complementary information about language plasticity and compensation.

The incidence and causes that may lead to an early end (unfinished cortical/subcortical mapping) of awake surgery for language mapping are little known. A study was conducted on 41 patients with brain glioma located in the language area that had awake surgery under conscious sedation. Surgery was ended early in 6 patients. The causes were: tonic-clonic seizure (1), lack of cooperation due to fatigue/sleep (4), whether or not word articulation was involved, a decreased level of consciousness for ammonia encephalopathy that required endotracheal intubation (1). There are causes that could be expected and in some cases avoided. Tumour size, preoperative aphasia, valproate treatment, and type of anaesthesia used are variables to consider to avoid failure in awake surgery for language mapping. With these results, the following measures are proposed: l) If the tumour is large, perform surgery in two times to avoid fatigue, 2) if patient has a preoperative aphasia, do not use sedation during surgery to ensure that sleepiness does not cause worse word articulation, 3) if the patient is on valproate treatment, it is necessary to rule out the pre-operative symptoms that are not due to ammonia encephalopathy.

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.

Objective The purpose of this study was to improve the surgical treatment of epilepsy by maximising seizure control while protecting language function. Methods A combined process of extra-operative electrical cortical stimulation (ECS) mapping, direct ECS and intra-operative continuous language assessment was performed during complicated operative cases. Of the 24 epilepsy patients, nine had a complex relationship between the seizure onset zone and the language cortices. The combined process was used in these nine patients. In the other 15 patients, surgical resection was completed based on extra-operative ECS results alone. Evaluations were performed before and after surgery to assess language function and seizure control. Results The intra-operative continuous language assessment provided important information at the time of the resection. Seven extra-operative ECS positive language sites were resected without obvious language deficits in two patients. Resection was interrupted by language disturbances in an area where no extra-operative ECS positive site was identified in one patient. In three other patients, functional boundary was undefined in extra-operative ECS result, epileptogenic cortices were maximally resected during the continuous language assessment. In terms of seizure control, 18 of 24 (75%) patients reached Engel's class I, including all nine patients who underwent intra-operative continuous language assessment. One patient had minor surgery-related language deficits three months after resection. Conclusions Intra-operative continuous language assessment proved to be complementary to extra-operative ECS mappings. The combination of ECS mappings and intra-operative continuous language assessment can maximise the resection of epileptogenic cortices and preserve language function in difficult cases involving the language cortex.

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.

Extraoperative electrocortical stimulation mapping (ESM) is used to identify functional cortex prior to epilepsy surgery, with the goal of preserving function postoperatively. Although attempts are made to avoid stimulation-evoked seizure activity, the clinical impact of these events with regard to safety, clinical utility, functional outcome, and even disruption to the procedure itself is unknown. We conducted a retrospective review of 57 patients with pharmacoresistant focal epilepsy who underwent intracranial electrode implantation and ESM. Stimulation-evoked seizures (afterdischarges associated with clinical signs or symptoms) occurred in 19 patients (33%). Mapping sessions were disrupted for 11 of these patients (i.e., 19% of the full sample and 58% of the subgroup of patients with stimulation-evoked seizures). Patients who had ESM disruption were no less likely than patients without ESM disruption to be seizure-free at one year (p = 0.63) and two years (p = 0.57) postoperatively. Among 23 patients who underwent language assessment pre- and postoperatively, 4 (17%) had evoked seizures that disrupted language mapping; these patients were no more likely to show postoperative language declines relative to those who had no ESM disruption (p = 0.26). Results suggest that evoked seizures occur frequently during ESM and can disrupt the procedure; however, these events do not appear to adversely affect postoperative outcomes. Nevertheless, attempts should be made to limit stimulation-evoked seizures in order to reduce patient discomfort, increase efficiency, and maximize the utility of ESM.

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.