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Repetitive TMS (rTMS) with a frequency of 5–10 Hz is widely used for language mapping. However, it may be accompanied by discomfort and is limited in the number and reliability of evoked language errors. We, here, systematically tested the influence of different stimulation frequencies (i.e., 10, 30, and 50 Hz) on tolerability, number, reliability, and cortical distribution of language errors aiming at improved language mapping. 15 right‐handed, healthy subjects (m = 8, median age: 29 yrs) were investigated in two sessions, separated by 2–5 days. In each session, 10, 30, and 50 Hz rTMS were applied over the left hemisphere in a randomized order during a picture naming task. Overall, 30 Hz rTMS evoked significantly more errors (20 ± 12%) compared to 50 Hz (12 ± 8%; p, The use of repetitive transcranial magnetic stimulation (rTMS) for language mapping is still hampered by a limited sensitivity and specificity, by an overall poor reliability and by stimulation‐associated discomfort. We, here, found that increasing the stimulation intensity up to 30 and 50 Hz can improve language mapping results as compared to the most commonly used protocol of 10 Hz rTMS.

OBJECTIVEEpilepsy affects neural processing and often causes intra- or interhemispheric language reorganization, rendering localization solely based on anatomical landmarks (e.g., Broca’s area) unreliable. Preoperative brain mapping is necessary to weigh the risk of resection with the risk of postoperative deficit. However, the use of conventional mapping methods (e.g., somatosensory stimulation, task-based functional MRI [fMRI]) in pediatric patients is technically difficult due to low compliance and their unique neurophysiology. Resting-state fMRI (rs-fMRI), a “task-free” technique based on the neural activity of the brain at rest, has the potential to overcome these limitations. The authors hypothesized that language networks can be identified from rs-fMRI by applying functional connectivity analyses.METHODSCases in which both task-based fMRI and rs-fMRI were acquired as part of the preoperative clinical protocol for epilepsy surgery were reviewed. Task-based fMRI consisted of 2 language tasks and 1 motor task. Resting-state fMRI data were acquired while the patients watched an animated movie and were analyzed using independent component analysis (i.e., data-driven method). The authors extracted language networks from rs-fMRI data by performing a similarity analysis with functionally defined language network templates via a template-matching procedure. The Dice coefficient was used to quantify the overlap.RESULTSThirteen children underwent conventional task-based fMRI (e.g., verb generation, object naming), rs-fMRI, and structural imaging at 1.5T. The language components with the highest overlap with the language templates were identified for each patient. Language lateralization results from task-based fMRI and rs-fMRI mapping were comparable, with good concordance in most cases. Resting-state fMRI–derived language maps indicated that language was on the left in 4 patients (31%), on the right in 5 patients (38%), and bilateral in 4 patients (31%). In some cases, rs-fMRI indicated a more extensive language representation.CONCLUSIONSResting-state fMRI–derived language network data were identified at the patient level using a template-matching method. More than half of the patients in this study presented with atypical language lateralization, emphasizing the need for mapping. Overall, these data suggest that this technique may be used to preoperatively identify language networks in pediatric patients. It may also optimize presurgical planning of electrode placement and thereby guide the surgeon’s approach to the epileptogenic zone.

Introduction: about 20% to 30% of patients with epilepsy are diagnosed with drug-resistant epilepsy and one third of these are candidates for epilepsy surgery. Surgical resection of the epileptogenic tissue is a well-established method for treating patients with intractable focal epilepsy. Determining language laterality and locality is an important part of a comprehensive epilepsy program before surgery. Functional Magnetic Resonance Imaging (fMRI) has been increasingly employed as a non-invasive alternative method for the Wada test and cortical stimulation. Sensitive and accurate language tasks are essential for any reliable fMRI mapping. Methods: The present study reviews the methods of presurgical fMRI language mapping and their dedicated fMRI tasks, specifically for patients with epilepsy. Results: Different language tasks including verbal fluency are used in fMRI to determine language laterality and locality in different languages such as Persian. there are some considerations including the language materials and technical protocols for task design that all presurgical teams should take into consideration. Conclusion: Accurate presurgical language mapping is very important to preserve patients language after surgery. This review was the first part of a project for designing standard tasks in Persian to help precise presurgical evaluation and in Iranian PWFIE.

Diffusive and progressive tumor infiltration within language-related areas of the brain induces functional reorganization. However, the macrostructural basis of subsequent language deficits is less clear. To address this issue, lesion topography data from 137 preoperative patients with left cerebral language-network gliomas (81 low-grade gliomas and 56 high-grade gliomas), were adopted for multivariate machine-learning-based lesion-language mapping analysis. We found that tumor location in the left posterior middle temporal gyrus—a bottleneck where both dorsal and ventral language pathways travel—predicted deficits of spontaneous speech (cluster size = 1356 mm3, false discovery rate corrected P

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.

Awake craniotomy with language mapping is being increasingly applied to avoid postoperative language dysfunctions worldwide. However, the effectiveness and reliability of this technique remain unclear due to the paucity of studies comparing the awake craniotomy with general anesthesia. To determine the benefit of awake craniotomy for language, motor, and neurological functions, as well as other clinical outcomes, we searched Medline, Embase, the Cochrane Library, and the Chinese Biomedical Literature Database up to December 2019. Gray literatures were also searched. We included randomized and non-randomized controlled studies comparing awake craniotomy versus general anesthetic resection and reporting the language and neurological outcomes. Ten studies with 833 patients were included in the meta-analysis. The pooled risk ratio (RR) suggested no significant differences in language and neurological outcomes between general anesthesia group and awake craniotomy group without electrical stimulation. Awake craniotomy with electrical stimulation, however, was associated with improved late language and neurological outcomes (≥ 3 months) versus general anesthesia with pooled RR of 0.44 (95% CI = 0.20–0.96) and 0.49 (95% CI = 0.30–0.79), respectively. Awake craniotomy with electrical stimulation was also associated with better extent of resection with the pooled RR of 0.81 (95%CI = 0.71–0.92) and shorter hospital stay duration with the pooled weighted mean difference (WMD) of − 1.14 (95%CI = − 1.80 to − 0.48). This meta-analysis suggested that the application of awake craniotomy with electrical stimulation during glioma resection is associated with lower risks of long-term neurological and language deficits and higher extent of tumor resection, as well as shorter hospital stay duration.

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.

Background Task-based functional MRI (tb-fMRI) is a well-established technique used to identify eloquent cortex, but has limitations, particularly in cognitively impaired patients who cannot perform language paradigms. Resting-state functional MRI (rs-fMRI) is a potential alternative modality for presurgical mapping of language networks that does not require task performance. The purpose of our study is to determine the utility of rs-fMRI for clinical preoperative language mapping when tb-fMRI is limited. Methods We retrospectively reviewed 134 brain tumor patients who underwent preoperative fMRI language mapping. rs-fMRI was post-processed with seed-based correlation (SBC) analysis, when language tb-fMRI was limited. Two neuroradiologists reviewed both the tb-fMRI and rs-fMRI results. Six neurosurgeons retrospectively rated the usefulness of rs-fMRI for language mapping in their patients. Results Of the 134 patients, 49 cases had limited tb-fMRI and rs-fMRI was post-processed. Two neuroradiologists found rs-fMRI beneficial for functional language mapping in 41(84%) and 43 (88%) cases respectively; Cohen’s kappa is 0.83, with a 95% confidence interval (0.61, 1.00). The neurosurgeons found rs-fMRI “definitely” useful in 26 cases (60%) and “somewhat” useful in 13 cases (30%) in locating potential eloquent language centers of clinical interest. Six unsuccessful rs-fMRI cases were due to: head motion (2 cases), nonspecific functionality connectivity outside the posterior language network (1 case), and an unknown system instability (3 cases). Conclusions This study is a proof of concept that shows SBC rs-fMRI may be a viable alternative for clinical language mapping when tb-fMRI is limited.

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.

Purpose The purported underutilization of magnetoencephalography (MEG) among the USA epilepsy centers has never been studied, and any evidence-based understanding of its magnitude is lacking. Methods Two hundred twenty-five National Association of Epilepsy Centers centers (2016) were invited to participate anonymously in a 13-question web-based survey of clinical practice focused on MEG use. Results On average, centers (N = 70; 61 of which were level 4) reported 7 dedicated epilepsy monitoring unit beds, 206 phase 1 studies, 15 phase 2 studies, 10 direct resections, and 9 indirect resections; 27% owned MEG. On average, 11.2 MEGs per year were ordered for epilepsy localization and 7.6 for any presurgical mapping modalities. Wada test aka the intracarotid sodium amobarbital procedure (ISAP) (43%) and functional MRI (29%) were preferred over MEG (4%) for language mapping. The number of epileptologists and the number of epilepsy monitoring unit beds correlated positively with the most clinical volumes. The centers who own a MEG had surgical volumes significantly higher than those without. The number and complexity of patients as well as the proximity of a MEG were perceived as significant contributors/obstacles to increased MEG use. Conclusions Only the centers with larger surgical volumes incorporate MEG regularly in presurgical evaluation of patients with drug-resistant epilepsy. A reversal of the pervasive underutilization of epilepsy surgery can benefit from MEG, but this requires a sustained concerted promotion by the epilepsy and MEG communities.

Background Maximal safe resection remains a key principle in infiltrating glioma management. Stimulation mapping is a key adjunct for minimizing functional morbidity while "fence-post" procedures use catheters or dye to mark the tumor border at the start of the procedure prior to brain shift. Objective To report a novel technique using stereotactically placed electrodes to guide tumor resection near critical descending subcortical fibers. Methods Navigated electrodes were placed prior to tumor resection along the deep margin bordering presumed eloquent tracts. Stimulation was administered through these depth electrodes for subcortical motor and language mapping. Results Twelve patients were included in this preliminary technical report. Seven patients (7/12, 58%) were in asleep cases, while the other 5 cases (5/12, 42%) were performed awake. Mapping of motor fibers was performed in 8 cases, and language mapping was done in 1 case. In 3 cases, both motor and language mapping were performed using the same depth electrode spanning corticospinal tract and the arcuate fasciculus. Conclusion Stereotactic depth electrode placement coupled with stimulation mapping of white matter tracts can be used concomitantly to demarcate the border between deep tumor margins and eloquent brain, thus helping to maximize extent of resection while minimizing functional morbidity.

Background Protocols for intraoperative language mapping with direct electrical stimulation (DES) often include various language tasks triggering both nouns and verbs in sentences. Such protocols are not readily available for navigated transcranial magnetic stimulation (nTMS), where only single word object naming is generally used. Here, we present the development, norming, and standardization of the verb and noun test for peri-operative testing (VAN-POP) that measures language skills more extensively. Methods The VAN-POP tests noun and verb retrieval in sentence context. Items are marked and balanced for several linguistic factors known to influence word retrieval. The VAN-POP was administered in English, German, and Dutch under conditions that are used for nTMS and DES paradigms. For each language, 30 speakers were tested. Results At least 50 items per task per language were named fluently and reached a high naming agreement. Conclusion The protocol proved to be suitable for pre- and intraoperative language mapping with nTMS and DES.

Neuronavigated repetitive transcranial magnetic stimulation (nrTMS) is an innovative technique that provides insight into language function with high accuracy in time and space. So far, nrTMS has mainly been applied in presurgical language mapping of patients with cranial neoplasms. For the present study nrTMS was used for language mapping in primary progressive aphasia Seven patients (median age: 70 years, 4 males) with the non-fluent variant of primary progressive aphasia were included in this pilot study. Inhibitory nrTMS trains (5 Hz, 40 % resting motor threshold) caused virtual lesions at 46 standardized cortical stimulation targets per hemisphere. Patients’ errors in a naming task during stimulation were counted. The majority of errors induced occurred during frontal lobe stimulation (34.3 %). Timing errors and non-responses were most frequent. More errors were induced in the right hemisphere (58%) than in the left hemisphere (42%). Mapping was tolerated by all patients, however, discomfort or pain was reported for stimulation of frontal areas. The elevated right-hemispheric error rate in our study supports the hypothesis of a partial shift of language function to the right hemisphere in neurodegenerative aphasia during the course of disease and therefore points to the existence of significant neuronal plasticity in primary progressive aphasia. While this is an interesting finding for neurodegenerative disorders per se, its promotion might also harbor future therapeutic targets.

Preoperative language mapping with navigated transcranial magnetic stimulation (nTMS) is currently based on the disruption of performance during object naming. The resulting cortical language maps, however, lack accuracy when compared to intraoperative mapping. The question arises whether nTMS results can be improved, when another language task is considered, involving verb retrieval in sentence context. Twenty healthy German speakers were tested with object naming and a novel action naming task during nTMS language mapping. Error rates and categories in both hemispheres were compared. Action naming showed a significantly higher error rate than object naming in both hemispheres. Error category comparison revealed that this discrepancy stems from more lexico-semantic errors during action naming, indicating lexico-semantic retrieval of the verb being more affected than noun retrieval. In an area-wise comparison, higher error rates surfaced in multiple right-hemisphere areas, but only trends in the left ventral postcentral gyrus and middle superior temporal gyrus. Hesitation errors contributed significantly to the error count, but did not dull the mapping results. Inclusion of action naming coupled with a detailed error analysis may be favorable for nTMS mapping and ultimately improve accuracy in preoperative planning. Moreover, the results stress the recruitment of both left- and right-hemispheric areas during naming., publishedVersion

Purpose fMRI is increasingly used for presurgical language mapping, but lack of standard methodology has made it difficult to combine/compare data across institutions or determine the relative efficacy of different approaches. Here, we describe a quantitative analytic framework for determining language laterality in clinical fMRI that addresses these concerns. Methods We retrospectively analyzed fMRI data from 59 patients who underwent presurgical language mapping at our institution with identical imaging and behavioral protocols. First, we compared the efficacy of different regional masks in capturing language activations. Then, we systematically explored how laterality indices (LIs) computed from these masks vary as a function of task and activation threshold. Finally, we determined the percentile threshold that maximized the correlation between the results of our LI approach and the laterality assessments from the original clinical radiology reports. Results First, we found that a regional mask derived from a meta-analysis of the fMRI literature better captured language task activations than masks based on anatomically defined language areas. Then, we showed that an LI approach based on this functional mask and percentile thresholding of subject activation can quantify the relative ability of different language tasks to lateralize language function at the population level. Finally, we determined that the 92nd percentile of subject-level activation provides the optimal LI threshold with which to reproduce the original clinical reports. Conclusion A quantitative framework for determining language laterality that uses a functionally-derived language mask and percentile thresholding of subject activation can combine/compare results across tasks and patients and reproduce clinical assessments of language laterality.

Navigated Transcranial Magnetic Stimulation (nTMS) is used to understand the cortical organization of language in preparation for the surgical removal of a brain tumor. Action naming with finite verbs can be employed for that purpose, providing additional information to object naming. However, little research has focused on the properties of the verbs that are used in action naming tasks, such as their status as transitive (taking an object; e.g., to read) or intransitive (not taking an object; e.g., to wink). Previous neuroimaging data show higher activation for transitive compared to intransitive verbs in posterior perisylvian regions bilaterally. In the present study, we employed nTMS and production of finite verbs to investigate the cortical underpinnings of transitivity. Twenty neurologically healthy native speakers of German participated in the study. They underwent language mapping in both hemispheres with nTMS. The action naming task with finite verbs consisted of transitive (e.g., The man reads the book) and intransitive verbs (e.g., The woman winks) and was controlled for relevant psycholinguistic variables. Errors were classified in four different error categories (i.e., non-linguistic errors, grammatical errors, lexico-semantic errors and, errors at the sound level) and were analyzed quantitatively. We found more nTMS-positive points in the left hemisphere, particularly in the left parietal lobe for the production of transitive compared to intransitive verbs. These positive points most commonly corresponded to lexico-semantic errors. Our findings are in line with previous aphasia and neuroimaging studies, suggesting that a more widespread network is used for the production of verbs with a larger number of arguments (i.e., transitives). The higher number of lexico-semantic errors with transitive compared to intransitive verbs in the left parietal lobe supports previous claims for the role of left posterior areas in the retrieval of argument structure information.

Background: Recently, electrocorticographic (ECoG) studies have emphasized the importance of gamma band-based functional mapping in the presurgical localization of the eloquent cortex. Passive functional mapping using ECoG signals provides a reliable method for identifying receptive language areas without many of the risks and limitations associated with electrical cortical stimulation. We report a surgical case of left temporal malignant glioma with intraoperative passive language mapping.Case Description: A 78-year-old woman was diagnosed with left temporal glioma with inspection of her language difficulty. MRI showed a left temporal tumor measuring 74.6 × 50.0 × 51.5 mm in size. Real-time CortiQ-based mapping using high-gamma activity by word-listening and story-listening tasks was performed. Significant listening task-evoked high gamma activities were detected in 5 channels in the superior temporal gyrus and one channel in the middle temporal gyrus. The tumor was grossly removed except for the region corresponding to listening task-evoked high gamma activities. Postoperatively, the patient's symptoms of language comprehension difficulty improved, and no new neurological deficits were observed.Conclusion: Intraoperative passive language mapping was successfully performed, and the patient's language function was well-preserved. Intraoperative passive language mapping, which is applicable in a short time and under general anesthesia, can be an important tool for detecting language areas.

BACKGROUND Functional mapping in awake craniotomy has the potential risk of electrical stimulation-related seizure. The authors have developed a novel mapping technique using a brain-cooling device. The cooling probe is cylindrical in shape with a thermoelectric cooling plate (10 × 10 mm) at the bottom. A proportional integration and differentiation-controlled system adjusts the temperature accurately (Japan patent no. P5688666). The authors used it in two patients with glioblastoma. Broca’s area was identified by electrical stimulation, and then the cooling probe set at 5°C was attempted on it. OBSERVATIONS Electrocorticogram was suppressed, and the temperature dropped to 8°C in 50 sec. A positive aphasic reaction was reproduced on Broca’s area at a latency of 7 sec. A negative reaction appeared on the adjacent cortices despite the temperature decrease. The sensitivity and specificity were 60% and 100%, respectively. No seizures or other adverse events related to the cooling were recognized, and no histological damage to the cooled cortex was observed. LESSONS The cooling probe suppressed topographical brain function selectively and reversibly. Awake functional mapping based on thermal neuromodulation technology could substitute or compensate for the conventional electrical mapping.

BACKGROUND Presurgical mapping of eloquent cortex in young patients undergoing neurosurgery is critical but presents challenges unique to the pediatric population, including motion artifact, noncompliance, and sedation requirements. Furthermore, as bilingualism in children increases, functional mapping of more than one language is becoming increasingly critical. Transcranial magnetic stimulation (TMS), a noninvasive brain stimulation technique, is well suited to evaluate language areas in children since it does not require the patient to remain still during mapping. OBSERVATIONS A 13-year-old bilingual male with glioblastoma multiforme involving the left parietal lobe and deep occipital white matter underwent preoperative language mapping using magnetic resonance imaging-guided TMS. Language-specific cortices were successfully identified in both hemispheres. TMS findings aided in discussing with the family the risks of postsurgical deficits of tumor resection; postoperatively, the patient had intact bilingual speech and was referred for chemotherapy and radiation. LESSONS The authors’ findings add to the evolving case for preoperative dual language mapping in bilingual neurosurgical candidates. The authors illustrate the feasibility and utility of TMS as a noninvasive functional mapping tool in this child. TMS is safe, effective, and can be used for preoperative mapping of language cortex in bilingual children to aid in surgical planning and discussion with families.

Resting‐state functional magnetic resonance imaging (rsfMRI) is a promising technique for language mapping that does not require task‐execution. This can be an advantage when language mapping is limited by poor task performance, as is common in clinical settings. Previous studies have shown that language maps extracted with rsfMRI spatially match their task‐based homologs, but no study has yet demonstrated the direct participation of the rsfMRI language network in language processes. This demonstration is critically important because spatial similarity can be influenced by the overlap of domain‐general regions that are recruited during task‐execution. Furthermore, it is unclear which processes are captured by the language network: does it map rather low‐level or high‐level (e.g., syntactic and lexico‐semantic) language processes? We first identified the rsfMRI language network and then investigated task‐based responses within its regions when processing stimuli of increasing linguistic content: symbols, pseudowords, words, pseudosentences and sentences. The language network responded only to language stimuli (not to symbols), and higher linguistic content elicited larger brain responses. The left fronto‐parietal, the default mode, and the dorsal attention networks were examined and yet none showed language involvement. These findings demonstrate for the first time that the language network extracted through rsfMRI is able to map language in the brain, including regions subtending higher‐level syntactic and semantic processes.

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.

Cortical stimulation mapping is the gold standard for presurgical language mapping; however, it cannot be reliably performed in very young patients. Language mapping using noninvasive modalities is also challenging in very young patients. Although utility of language mapping using power of high-gamma in electrocorticographic recordings was demonstrated in adults and older children, there is a gap of knowledge in the ability of this procedure for localizing language-specific cortex in very young patients. We describe a case of a 2-year-old patient who, to our knowledge, is the youngest person to undergo successful high-gamma electrocorticographic presurgical language mapping for localization of the expressive language cortex (Broca area). The surgical plan was to resect a cortical tuber within the left inferior frontal gyrus and there was a strong concern about postoperative language deficit after resection. Presurgical language mapping using noninvasive modalities were attempted without success. Cortical stimulation mapping was not feasible in this patient. Therefore, high-gamma electrocorticography was the only viable option for language mapping, and it successfully localized the expressive language cortex. The patient underwent surgery for resection of the IFG tuber based on results of high-gamma electrocorticography and had no postoperative language deficit. High-gamma electrocorticography can be used for localizing language-specific cortex, especially Broca’s area, in very young patients.

Awake craniotomy with intraoperative neurophysiological language mapping (INLM) is an established procedure for patients undergoing surgery to resection tumors in the language cortex area. INLM and continuous neurophysiological monitoring allow assessment of the language function, which is not possible under general anesthesia. INLM of the brain areas provides a helpful tool to the operating surgeon in reducing the risks associated with tumor resection in the motor and language cortex. We present a literature review and the technical method used for INLM by utilizing direct electrical cortical stimulation. We also report the usefulness of INLM for evaluation of the language function during resection of cortical tumors, epilepsy foci, and arteriovenous malformations (AVMs) located near language areas. First, the central sulcus is identified by sensory mapping, followed by the motor cortex's identification by direct electrical cortical stimulation (DECS). Neurological assessment of the patient is done by auditory and visual feedback. The patient is asked to repeat numbers, days, words, sentences, read words, and name pictures during cortical stimulation. DECS may cause a slurring or speech arrest. Electrocorticography (ECoG) is also performed during cortical stimulation to identify any after-discharges. Examination of the patient occurs immediately after surgery, and then 24 hours, one week, six months, and 12 months postoperatively. Bipolar DECS for motor mapping with ECoG can safely and reliably be utilized to identify essential language areas with minimizing permanent language deficits and maximizing the extent of tumor resection.

Accurate presurgical mapping of motor, speech, and language cortices, while crucial for neurosurgical planning and minimizing post-operative functional deficits, is challenging in young children with neurological disease. In such children, both invasive (cortical stimulation mapping) and non-invasive functional mapping imaging methods (MEG, fMRI) have limited success, often leading to delayed surgery or adverse post-surgical outcomes. We therefore examined the clinical utility of transcranial magnetic stimulation (TMS) in young children who require functional mapping. In a retrospective chart review of TMS studies performed on children with refractory epilepsy or a brain tumor, at our institution, we identified 47 mapping sessions in 36 children 3 years of age or younger, in whom upper and lower extremity motor mapping was attempted; and 13 children 5–6 years old in whom language mapping, using a naming paradigm, was attempted. The primary hand motor cortex was identified in at least one hemisphere in 33 of 36 patients, and in both hemispheres in 27 children. In 17 children, primary leg motor cortex was also successfully identified. The language cortices in temporal regions were successfully mapped in 11 of 13 patients, and in six of them language cortices in frontal regions were also mapped, with most children (n = 5) showing right hemisphere dominance for expressive language. Ten children had a seizure that was consistent with their clinical semiology during or immediately following TMS, none of which required intervention or impeded completion of mapping. Using TMS, both normal motor, speech, and language developmental patterns and apparent disease induced reorganization were demonstrated in this young cohort. The successful localization of motor, speech, and language cortices in young children improved the understanding of the risk-benefit ratio prior to surgery and facilitated surgical planning aimed at preserving motor, speech, and language functions. Post-operatively, motor function was preserved or improved in nine out of 11 children who underwent surgery, as was language function in all seven children who had surgery for lesions near eloquent cortices. We provide feasibility data that TMS is a safe, reliable, and effective tool to map eloquent cortices in young children.

Background:The simplistic approaches to language circuits are continuously challenged by new findings in brain structure and connectivity. The posterior middle frontal gyrus and area 55b (pFMG/area55b), in particular, has gained a renewed interest in the overall language network.Methods:This is a retrospective single-center cohort study of patients who have undergone awake craniotomy for tumor resection. Navigated transcranial magnetic simulation (nTMS), tractography, and intraoperative findings were correlated with language outcomes.Results:Sixty-five awake craniotomies were performed between 2012 and 2020, and 24 patients were included. nTMS elicited 42 positive responses, 76.2% in the inferior frontal gyrus (IFG), and hesitation was the most common error (71.4%). In the pMFG/area55b, there were seven positive errors (five hesitations and two phonemic errors). This area had the highest positive predictive value (43.0%), negative predictive value (98.3%), sensitivity (50.0%), and specificity (99.0%) among all the frontal gyri. Intraoperatively, there were 33 cortical positive responses—two (6.0%) in the superior frontal gyrus (SFG), 15 (45.5%) in the MFG, and 16 (48.5%) in the IFG. A total of 29 subcortical positive responses were elicited−21 in the deep IFG–MFG gyri and eight in the deep SFG–MFG gyri. The most common errors identified were speech arrest at the cortical level (20 responses−13 in the IFG and seven in the MFG) and anomia at the subcortical level (nine patients—eight in the deep IFG–MFG and one in the deep MFG–SFG). Moreover, 83.3% of patients had a transitory deterioration of language after surgery, mainly in the expressive component (p= 0.03). An increased number of gyri with intraoperative positive responses were related with better preoperative (p= 0.037) and worse postoperative (p= 0.029) outcomes. The involvement of the SFG–MFG subcortical area was related with worse language outcomes (p= 0.037). Positive nTMS mapping in the IFG was associated with a better preoperative language outcome (p= 0.017), relating to a better performance in the expressive component, while positive mapping in the MFG was related to a worse preoperative receptive component of language (p= 0.031).Conclusion:This case series suggests that the posterior middle frontal gyrus, including area 55b, is an important integration cortical hub for both dorsal and ventral streams of language.

Stereo-electroencephalography (sEEG) is a method that uses stereotactically implanted depth electrodes for extra-operative mapping of epileptogenic and functional networks. sEEG derived functional mapping is achieved using electrical cortical stimulations (ECS) that are currently the gold standard for delineating eloquent cortex. As this stands true especially for primary cortices (e.g., visual, sensitive, motor, etc.), ECS applied to higher order brain areas determine more subtle behavioral responses. While anterior and posterior language areas in the dorsal language stream seem to share characteristics with primary cortices, basal temporal language area (BTLA) in the ventral temporal cortex (VTC) behaves as a highly associative cortex. After a short introduction and considerations about methodological aspects of ECS using sEEG, we review the sEEG language mapping literature in this perspective. We first establish the validity of this technique to map indispensable language cortices in the dorsal language stream. Second, we highlight the contrast between the growing empirical ECS experience and the lack of understanding regarding the fundamental mechanisms underlying ECS behavioral effects, especially concerning the dispensable language cortex in the VTC. Evidences for considering network architecture as determinant for ECS behavioral response complexities are discussed. Further, we address the importance of designing new research in network organization of language as this could enhance ECS ability to map interindividual variability, pathology driven reorganization, and ultimately identify network resilience markers in order to better predict post-operative language deficit. Finally, based on a whole body of available studies, we believe there is strong evidence to consider sEEG as a valid, safe and reliable method for defining eloquent language cortices although there have been no proper comparisons between surgical resections with or without extra-operative or intra-operative language mapping.

(1) Background—Mapping language using direct cortical stimulation (DCS) during an awake craniotomy is difficult without using more than one language paradigm that particularly follows the demand of DCS by not exceeding the assessment time of 4 s to prevent intraoperative complications. We designed an intraoperative language paradigm by combining classical picture naming and verb generation, which safely engaged highly relevant language functions. (2) Methods—An evaluation study investigated whether a single trial of the language task could be performed in less than 4 s in 30 healthy subjects and whether the suggested language paradigm sufficiently pictured the cortical language network using functional magnetic resonance imaging (fMRI) in 12 healthy subjects. In a feasibility study, 24 brain tumor patients conducted the language task during an awake craniotomy. The patients’ neuropsychological outcomes were monitored before and after surgery. (3) Results—The fMRI results in healthy subjects showed activations in a language-associated network around the (left) sylvian fissure. Single language trials could be performed within 4 s. Intraoperatively, all tumor patients showed DCS-induced language errors while conducting the novel language task. Postoperatively, mild neuropsychological impairments appeared compared to the presurgical assessment. (4) Conclusions—These data support the use of a novel language paradigm that safely monitors highly relevant language functions intraoperatively, which can consequently minimize negative postoperative neuropsychological outcomes.

Visualization of functionally significant subcortical white matter fibers is needed in neurosurgical procedures in order to avoid damage to the language network during resection. In an effort to achieve this, positive cortical points revealed during preoperative language mapping with navigated transcranial magnetic stimulation (nTMS) can be employed as regions of interest (ROIs) for diffusion tensor imaging (DTI) fiber tracking. However, the effect that the use of different language tasks has on nTMS mapping and subsequent DTI-fiber tracking remains unexplored. The visualization of ventral stream tracts with an assumed lexico-semantic role may especially benefit from ROIs delivered by the lexico-semantically demanding verb task, Action Naming. In a first step, bihemispheric nTMS language mapping was administered in 18 healthy participants using the standard task Object Naming and the novel task Action Naming to trigger verbs in a small sentence context. Cortical areas in which nTMS induced language errors were identified as language-positive cortical sites. In a second step, nTMS-based DTI-fiber tracking was conducted using solely these language-positive points as ROIs. The ability of the two tasks’ ROIs to visualize the dorsal tracts Arcuate Fascicle and Superior Longitudinal Fascicle, the ventral tracts Inferior Longitudinal Fascicle, Uncinate Fascicle, and Inferior Fronto-Occipital Fascicle, the speech-articulatory Cortico-Nuclear Tract, and interhemispheric commissural fibers was compared in both hemispheres. In the left hemisphere, ROIs of Action Naming led to a significantly higher fraction of overall visualized tracts, specifically in the ventral stream’s Inferior Fronto-Occipital and Inferior Longitudinal Fascicle. No difference was found between tracking with Action Naming vs. Object Naming seeds for dorsal stream tracts, neither for the speech-articulatory tract nor the inter-hemispheric connections. While the two tasks appeared equally demanding for phonological-articulatory processes, ROI seeding through the task Action Naming seemed to better visualize lexico-semantic tracts in the ventral stream. This distinction was not evident in the right hemisphere. However, the distribution of tracts exposed was, overall, mirrored relative to those in the left hemisphere network. In presurgical practice, mapping and tracking of language pathways may profit from these findings and should consider inclusion of the Action Naming task, particularly for lesions in ventral subcortical regions., publishedVersion

Preoperative mapping of cortical structures prior to neurosurgical intervention can provide a roadmap of the brain with which neurosurgeons can navigate critical cortical structures. In patients undergoing surgery for brain tumors, preoperative mapping allows for improved operative planning, patient risk stratification, and personalized preoperative patient counseling. Navigated transcranial magnetic stimulation (nTMS) is one modality that allows for highly accurate, image-guided, non-invasive stimulation of the brain, thus allowing for differentiation between eloquent and non-eloquent cortical regions. Motor mapping is the best validated application of nTMS, yielding reliable maps with an accuracy similar to intraoperative cortical mapping. Language mapping is also commonly performed, although nTMS language maps are not as highly concordant with direct intraoperative cortical stimulation maps as nTMS motor maps. Additionally, nTMS has been used to localize cortical regions involved in other functions such as facial recognition, calculation, higher-order motor processing, and visuospatial orientation. In this review, we evaluate the growing literature on the applications of nTMS in the preoperative setting. First, we analyze the evidence in support of the most common clinical applications. Then we identify usages that show promise but require further validation. We also discuss developing nTMS techniques that are still in the experimental stage, such as the use of nTMS to enhance postoperative recovery. Finally, we highlight practical considerations when utilizing nTMS and, importantly, its safety profile in neurosurgical patients. In so doing, we aim to provide a comprehensive review of the role of nTMS in the neurosurgical management of a patient with a brain tumor.

Graphical abstract, Highlights • Counting is used in Electrical Stimulation Mapping (ESM), often as a language screen. • We report a case where ESM reliably disrupted production of letters, but not numbers. • Counting is not an accurate screen of all language functions in ESM., Neurosurgery has the potential to cure patients with drug-resistant focal epilepsy, but carries the risk of permanent language impairment when surgery involves the dominant hemisphere of the brain. This risk can be estimated and minimized using electrical stimulation mapping (ESM), which uses cognitive and linguistic tasks during cortical ESM to differentiate “eloquent” and “resectable” areas in the brain. One such task, counting, is often used to screen and characterize language during ESM in patients whose language abilities are limited. Here we report a patient with drug-resistant epilepsy arising from the language-dominant hemisphere using fMRI. Our patient experienced loss of the ability to recite or write the alphabet, but not to count, during ESM of the dominant left posterior superior temporal gyrus. This selective impairment extended to both spoken and written production. We suggest the need for caution when using counting as a sole means to screen language function and as a method of testing low functioning patients using ESM.

BACKGROUND: Functional MRI improves preoperative planning in patients with brain tumors, but task-correlated signal intensity changes are only 2%–3% above baseline. This makes accurate functional mapping challenging. Marchenko-Pastur principal component analysis (MP-PCA) provides a novel strategy to separate functional MRI signal from noise without requiring user input or prior data representation. PURPOSE: To determine whether MP-PCA denoising improves activation magnitude for task-based functional MRI language mapping in patients with brain tumors. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act–compliant study, MP-PCA performance was first evaluated by using simulated functional MRI data with a known ground truth. Right-handed, left-language–dominant patients with brain tumors who successfully performed verb generation, sentence completion, and finger tapping functional MRI tasks were retrospectively identified between January 2017 and August 2018. On the group level, for each task, histograms of z scores for original and MP-PCA denoised data were extracted from relevant regions and contralateral homologs were seeded by a neuroradiologist blinded to functional MRI findings. Z scores were compared with paired two-sided t tests, and distributions were compared with effect size measurements and the Kolmogorov-Smirnov test. The number of voxels with a z score greater than 3 was used to measure task sensitivity relative to task duration. RESULTS: Twenty-three patients (mean age ± standard deviation, 43 years ± 18; 13 women) were evaluated. MP-PCA denoising led to a higher median z score of task-based functional MRI voxel activation in left hemisphere cortical regions for verb generation (from 3.8 ± 1.0 to 4.5 ± 1.4; P < .001), sentence completion (from 3.7 ± 1.0 to 4.3 ± 1.4; P < .001), and finger tapping (from 6.9 ± 2.4 to 7.9 ± 2.9; P < .001). Median z scores did not improve in contralateral homolog regions for verb generation (from −2.7 ± 0.54 to −2.5 ± 0.40; P = .90), sentence completion (from −2.3 ± 0.21 to −2.4 ± 0.37; P = .39), or finger tapping (from −2.3 ± 1.20 to −2.7 ± 1.40; P = .07). Individual functional MRI task durations could be truncated by at least 40% after MP-PCA without degradation of clinically relevant correlations between functional cortex and functional MRI tasks. CONCLUSION: Denoising with Marchenko-Pastur principal component analysis led to higher task correlations in relevant cortical regions during functional MRI language mapping in patients with brain tumors. © RSNA, 2020 Online supplemental material is available for this article.

This chapter explores the applications of magnetoencephalography (MEG) to the study of the brain mechanisms for language functions. Language mapping with MEG has proved helpful in presurgical estimates of the location and extent of language-related cortex as well as in the intraoperative identification of these cortical patches. In fact, in several neurosurgical centers around the world, such assessments are part of the protocol of surgical interventions, especially in the case of epilepsy. Moreover, MEG alone or in combination with other imaging methods, such as functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS), is extensively used for the testing of alternative models of cortical organization for language in normal populations. However, applications of MEG to language mapping face most of the limitations that characterize brain imaging techniques relying on hemodynamic measures. Perhaps the most fundamental of these limitations concerns the degree of specificity of results: Activation profiles feature brain regions that may not be indispensable for a particular target function. This problem is particularly serious in the case of language mapping and to a lesser degree in motor cortex mapping.

OBJECTIVE Intraoperative tasks for awake language mapping are typically selected based on the language tracts that will likely be encountered during tumor resection. However, diminished attention and arousal secondary to perioperative sedatives may reduce a task’s usefulness for identifying eloquent cortex. For instance, accuracy in performing select language tasks may be high preoperatively but decline in the operating room. In the present study, the authors sought to identify language tasks that can be performed with high accuracy in both situational contexts so the neurosurgical team can be confident that speech errors committed during awake language mapping result from direct cortical stimulation to eloquent cortex, rather than from poor performance in general. METHODS We administered five language tasks to 44 patients: picture naming (PN), text reading (TR), auditory object naming (AN), repetition of 4-syllable words (4SYL), and production of syntactically intact sentences (SYNTAX). Performance was assessed using the 4-point scale of the quick aphasia battery 24 hours preoperatively and intraoperatively. We next determined whether or not accuracy on each task was higher preoperatively than intraoperatively. We also determined whether 1) intraoperative accuracy on a given task predicted intraoperative performance on the other tasks and 2) low preoperative accuracy on a task predicted a decrease in accuracy intraoperatively. RESULTS Relative to preoperative accuracy, intraoperative accuracy declined on PN (3.90 vs 3.82, p = 0.0001), 4SYL (3.96 vs 3.91, p = 0.0006), and SYNTAX (3.85 vs 3.67, p = 0.0001) but not on TR (3.96 vs 3.94, p = 0.13) or AN (3.70 vs 3.58, p = 0.058). Intraoperative accuracy on PN and AN independently predicted intraoperative accuracy on the remaining language tasks (p < 0.001 and p < 0.01, respectively). Finally, low preoperative accuracy on SYNTAX predicted a decrease in accuracy on this task intraoperatively (R2 = 0.36, p = 0.00002). CONCLUSIONS While TR lacks sensitivity in identifying language deficits at baseline, accuracy on TR is stable across testing settings. Baseline accuracy on the other four of our five language tasks was not predictive of intraoperative performance, signifying the need to repeat language tests prior to stimulation mapping to confirm reliability.

Intraoperative language mapping of tumor and peritumor tissue is a well-established technique for avoiding permanent neurological deficits and maximizing extent of resection. Although there are several components of language that may be tested intraoperatively (eg, naming, writing, reading, and repetition), there is a lack of consistency in how patients are tested intraoperatively as well as the techniques involved to ensure safety during an awake procedure. Here, we review appropriate patient selection, neuroanesthetic techniques, cortical and subcortical language mapping stimulation paradigms, and selection of intraoperative language tasks used during awake craniotomies. We also expand on existing language mapping reviews by considering how intensity and timing of electrical stimulation may impact interpretation of mapping results.

Nowadays, numerous neuropsychological tests are available for multidisciplinary teams to perform awake brain surgery but none-or very few-of them constitutes a mandatory prerequisite. No consensus has been reached about the choice of intraoperative tests, which can be relatively simple for certain primary functions, but can be much more difficult for high-level cognitive functions. This review aims to give an overview about the assessment of language during awake brain surgery in adults and focus on the analysis of the different language protocols that have been published, to compile the most used standardized tests that evaluate different linguistic cognitive processes. We performed a systematic review about awake brain surgery studies that mentioned a specific test or protocol for assessing language in adults from the last 15 years. The search yielded 3,504 articles. 120 studies reported a linguistic protocol or test. This review allowed to obtain a defined neuropsychological picture of the essential tasks that a linguistic protocol in awake surgery should compile. This review will help clinicians in selecting tasks for monitoring cognition during awake brain surgery as well as contributes to enlighten the efficacy of linguistics protocols in order to minimize language deficits in awake surgery.

We aimed to investigate clinical parameters that affected the results of navigated repetitive transcranial magnetic stimulation (nrTMS) language mapping by comparing the results of preoperative nrTMS language mapping with those of direct cortical stimulation (DCS) mapping. In the prospective, non-randomized study, patients had to meet all of the following inclusion criteria: the presence of left- or right-side brain tumors in the vicinity of or inside the areas anatomically associated with language functions; awake brain surgery scheduled; and age >18 years. Sixty one patients were enrolled, and this study included 42 low-grade gliomas and 19 high-grade gliomas (39 men, 22 women; mean age, 41.1 years, range 18–72 years). The tumor was located in the left and right hemisphere in 50 (82.0%) and 11 (18.0%) patients, respectively. In the 50 patients with left-side gliomas, nrTMS language mapping showed 81.6% sensitivity, 59.6% specificity, 78.5% positive predictive value, and 64.1% negative predictive value when compared with the respective DCS values for detecting language sites in all regions. We then investigated how some parameters, including age, tumor type, tumor volume, and the involvement of anatomical language-related regions, affected different subpopulations. Based on the receiver operating curve statistics, subgroup analysis showed that the non-involvement of language-related regions afforded significantly better the area under the curve (AUC) values (AUC = 0.81, 95% confidence interval (CI): 0.74–0.88) than the involvement of language-related regions (AUC = 0.58, 95% CI: 0.50–0.67; p

We read with great interest the article entitled, “Lesion-Specific Language Network Alterations in Temporal Lobe Epilepsy,” by Foesleitner et al.[1][1] Functional connectivity, often synonymously used in reference to “resting-state functional connectivity,” offers a unique insight into brain

Navigated transcranial magnetic stimulation (nTMS) is increasingly applied in language mapping. However, the application mode and task selection of nTMS are not standardized. The aim of this study was to assessed the necessity and validity of multitask nTMS language mapping by comparing results with extraoperative electrical cortical stimulation (eoECS). In this study, sixteen epilepsy surgery patients were examined by nTMS and eoECS language mapping, and the two results were compared. The mapping results were validated with pre- to postoperative language assessments. Compared with eoECS, nTMS showed the overall sensitivity of 82.4%, specificity of 95.1%, positive predictive value of 66.7%, and negative predictive value of 97.8%. Spontaneous speech was the most sensitive task in the frontal area, naming was the sensitive task in both frontal and temporal areas. The false responses were mainly located in the perisylvian region. Multitask nTMS helps to reduce missing language relevant cortex preoperatively. Selecting spontaneous speech and naming tasks in frontal area, comprehension and naming tasks in temporal and posterior language area would strike the balance between the validity and efficiency of the mapping procedure. These results manifested the necessity of applying multitask in nTMS language mapping. Our study highlighted the importance of the nTMS evaluation mode and task selection for epilepsy patients.

OBJECTIVE The authors assessed the clinical relevance of preoperative task-induced high-frequency activity (HFA) for language mapping in patients with refractory epilepsy during stereoelectroencephalography recording. Although HFA evaluation was described as a putative biomarker of cognition, its clinical relevance for mapping language networks was assessed predominantly by studies using electrocorticography (ECOG). METHODS Forty-two patients with epilepsy who underwent intracranial electrode implantation during both task-induced HFA and direct cortical stimulation (DCS) language mapping were evaluated. The spatial and functional relevance of each method in terms of specificity and sensitivity were evaluated. RESULTS The results showed that the two methods were able to map classic language regions, and a large and bilateral language network was obtained with induced HFA. At a regional level, differences were observed between methods for parietal and temporal lobes: HFA recruited a larger number of cortical parietal sites, while DCS involved more cortical temporal sites. Importantly, the results showed that HFA predicts language interference induced by DCS with high specificity (92.4%; negative predictive value 95.9%) and very low sensitivity (8.9%; positive predictive value 4.8%). CONCLUSIONS DCS language mapping appears to be more appropriate for an extensive temporal mapping than induced HFA mapping. Furthermore, induced HFA should be used as a complement to DCS to preselect the number of stimulated sites during DCS, by omitting those reported as HFA−. This may be a considerable advantage because it allows a reduction in the duration of the stimulation procedure. Several parameters to be used for each method are discussed and the results are interpreted in relation to previous results reported in ECOG studies.

Repetitive TMS (rTMS) allows to non-invasively and transiently disrupt local neuronal functioning. Its potential for mapping of language function is currently explored. Given the inter-individual heterogeneity of tumor impact on the language network and resulting rTMS derived functional mapping, we propose to use machine learning strategies to classify potential patterns of functional reorganization. We retrospectively included 90 patients with left perisylvian glioma tumors, world health organization (WHO) grade II-IV, affecting the language network. All patients underwent navigated rTMS language mappings. The severity of aphasia was assessed preoperatively using the Berlin Aphasia Score (BAS), which is adapted to the Aachener Aphasia Test (AAT). After spatial normalization to MNI 152 of all rTMS spots, we calculated the error rate (ER) in each cortical area by automated anatomical labeling parcellation (AAL) and used support vector machine (SVM) as a classifier for significant areas in relation to aphasia. 29 of 90 (32.2%) patients suffered from aphasia. Univariate analysis revealed 11 perisylvian AVOIs’ ERs (eight left, three right hemispheric) that were significantly higher in the aphasic than non-aphasic group (p < 0.05), depicting a broad, bihemispheric language network. After feeding the significant AVOIs into the SVM model, it showed that additional to age (w = 2.95), the ERs of right Frontal_Inf_Tri (w = 2.06) and left SupraMarginal (w = 2.05) and Parietal_Inf (w= 1.80) contributed more than other features to the model. The model’s sensitivity was 89.7%, the specificity was 82.0%, the overall accuracy was 81.1% and AUC was 88.7%. Our results demonstrate an increased vulnerability of the right inferior frontal gyrus to rTMS in patients suffering from aphasia due to left perisylvian gliomas. This confirms a functional relevant involvement of the right frontal area in relation to aphasia. While age as a feature improved our SVM model the most, the tumor location feature didn’t affect the SVM model. This finding indicates that general tumor induced network disconnection is relevant to aphasia and not necessarily related to specific lesion locations. Additionally, our results emphasize the decreasing potential for neuroplasticity with age.

OBJECTIVEBy looking at how the accuracy of preoperative brain mapping methods vary according to differences in the distance from the activation clusters used for the analysis, the present study aimed to elucidate how preoperative functional neuroimaging may be used in such a way that maximizes the mapping accuracy.METHODSThe eloquent function of 19 patients with a brain tumor or cavernoma was mapped prior to resection with both functional MRI (fMRI) and magnetoencephalography (MEG). The mapping results were then validated using direct cortical stimulation mapping performed immediately after craniotomy and prior to resection. The subset of patients with equivalent MEG and fMRI tasks performed for motor (n = 14) and language (n = 12) were evaluated as both individual and combined predictions. Furthermore, the distance resulting in the maximum accuracy, as evaluated by the J statistic, was determined by plotting the sensitivities and specificities against a linearly increasing distance threshold.RESULTSfMRI showed a maximum mapping accuracy at 5 mm for both motor and language mapping. MEG showed a maximum mapping accuracy at 40 mm for motor and 15 mm for language mapping. At the standard 10-mm distance used in the literature, MEG showed a greater specificity than fMRI for both motor and language mapping but a lower sensitivity for motor mapping. Combining MEG and fMRI showed a maximum accuracy at 15 mm and 5 mm—MEG and fMRI distances, respectively—for motor mapping and at a 10-mm distance for both MEG and fMRI for language mapping. For motor mapping, combining MEG and fMRI at the optimal distances resulted in a greater accuracy than the maximum accuracy of the individual predictions.CONCLUSIONSThis study demonstrates that the accuracy of language and motor mapping for both fMRI and MEG is heavily dependent on the distance threshold used in the analysis. Furthermore, combining MEG and fMRI showed the potential for increased motor mapping accuracy compared to when using the modalities separately.Clinical trial registration no.: NCT01535430 (clinicaltrials.gov)

We report a 41- year-old, left-handed patient with drug-resistant right temporal lobe epilepsy (TLE). Presurgical fMRI was conducted to examine whether the patient had language functioning in the right hemisphere given that left-handedness is associated with a higher prevalence of right hemisphere dominance for language. The fMRI results revealed bilateral activation in Broca's and Wernicke's areas and activation of eloquent cortex near the region of planned resection in the right temporal lobe. Due to right temporal language-related activation, the patient underwent an awake right-sided temporal lobectomy with intraoperative language mapping. Intraoperative direct cortical stimulation (DCS) was conducted in the regions corresponding to the fMRI activation, and the patient showed language abnormalities, such as paraphasic errors, and speech arrest. The decision was made to abort the planned anterior temporal lobe procedure, and the patient instead underwent a selective amygdalohippocampectomy via the Sylvian fissure at a later date. Post-operatively the patient was seizure-free with no neurological deficits. Taken together, the results support previous findings of right hemisphere language activation in left-handed individuals, and should be considered in cases in which presurgical localization is conducted for left-hand dominant patients undergoing neurosurgical procedures., Highlights • The report evaluates evidence for the possibility of right hemisphere language activation in a left-handed right TLE patient • The results of the fMRI tasks showed bilateral speech regions, such as left and right Broca's area and Wernicke's area • The results support previous findings of right hemisphere language activation in left-handed individuals • The report discusses the value of fMRI of language tasks for presurgical planning in epilepsy cases • Report highlights how fMRI findings can alter surgical strategy and how intraoperative brain mapping validates these findings

The left frontal aslant tract (FAT) has been proposed to be relevant for language, and specifically for spontaneous speech fluency. However, there is missing causal evidence that stimulation of the FAT affects spontaneous speech, and not language production in general. We present a series of 12 neurosurgical cases with awake language mapping of the cortex near the left FAT. Tasks for language mapping included the commonly used action picture naming, and sentence completion, tapping more specifically into spontaneous speech. A task dissociation was found in 10 participants: while being stimulated on specific sites, they were able to name a picture but could not complete a sentence. Overlaying of these sites on preoperative white-matter tract reconstructions revealed that in each individual case they were located on cortical terminations of the FAT. This corroborates the language functional specificity of the left FAT as a tract underlying fluent spontaneous speech.

BACKGROUND AND PURPOSE: Previous literature has demonstrated disparity in the post-operative recovery of first and second language function of bilingual neurosurgical patients. However, it is unclear to whether pre-operative brain mapping of both languages is needed. In this study, we aimed to evaluate the clinical utility of language task functional MRI (fMRI) implemented in both languages in bilingual patients. METHODS: We retrospectively examined fMRI data of thirteen bilingual brain tumor patients (age: 23 to 59 years) who performed antonym generation task-based fMRIs in English and non-English language. The usefulness of bilingual language mapping was evaluated using a structured survey administered to five neurosurgeons. Additionally, quantitative comparison between the brain activation maps of both languages was performed. RESULTS: Survey responses revealed differences in raters’ surgical approach, including asleep vs. awake surgery and extent of resection, after viewing the language fMRI maps. Additional non-English fMRI led to changes in surgical decision-making and bettered localization of language areas. Quantitative analysis revealed an increase in laterality index (LI) in non-English fMRI compared to English fMRI. The Dice coefficient demonstrated fair overlap (0.458 +/− 0.160) between the activation maps. CONCLUSION: Bilingual fMRI mapping of bilingual patients allows to better appreciate functionally active language areas that may be neglected in single language mapping. Utility of bilingual mapping was supported by changes in both surgical approach and LI measurements, suggesting its benefit on pre-operative language mapping.

The role of language in communication plays a crucial role in human development and function. In patients who have a surgical lesion at the functional language areas, surgery should be intricately planned to avoid incurring further morbidity. This normally requires extensive functional and anatomical mappings of the brain to identify regions that are involved in language processing and production. In our case report, regions of the brain that are important for language functions were studied before surgery by employing (a) extraoperative methods such as functional magnetic resonance imaging, transmagnetic stimulation, and magnetoencephalography; (b) during the surgery by utilizing intraoperative awake surgical methods such as an intraoperative electrical stimulation; and (c) a two-stage surgery, in which electrical stimulation and first mapping are made thoroughly in the ward before second remapping during surgery. The extraoperative methods before surgery can guide the neurosurgeon to localize the functional language regions and tracts preoperatively. This will be confirmed using single-stage intraoperative electrical brain stimulation during surgery or a two-stage electrical brain stimulation before and during surgery. Here, we describe two cases in whom one has a superficial lesion and another a deep-seated lesion at language-related regions, in which language mapping was done to preserve its function. Additional review on the neuroanatomy of language regions, language network, and its impairment was also described.

Summary Objective Navigated transcranial magnetic stimulation (nTMS) is becoming increasingly popular in noninvasive preoperative language mapping, as its results correlate well enough with those obtained by direct cortical stimulation (DCS) during awake surgery in adult patients with tumor. Reports in the context of epilepsy surgery or extraoperative DCS in adults are, however, sparse, and validation of nTMS with DCS in children is lacking. Furthermore, little is known about the risk of inducing epileptic seizures with nTMS in pediatric epilepsy patients. We provide the largest validation study to date in an epilepsy surgery population. Methods We compared language mapping with nTMS and extraoperative DCS in 20 epilepsy surgery patients (age range 9‐32 years; 14 children and adolescents). Results In comparison with DCS, sensitivity of nTMS was 68 specificity 76 positive predictive value 27 and negative predictive value 95 Age, location of ictal‐onset zone near or within DCS‐mapped language areas or severity of cognitive deficits had no significant effect on these values. None of our patients had seizures during nTMS. Significance Our study suggests that nTMS language mapping is clinically useful and safe in epilepsy surgery patients, including school‐aged children and patients with extensive cognitive dysfunction. Similar to in tumor surgery, mapping results in the frontal region are most reliable. False negative findings may be slightly more likely in epilepsy than in tumor surgery patients. Mapping results should always be verified by other methods in individual patients.

Electrical stimulation mapping (ESM) is considered the gold standard for identification of essential language cortex and is especially important in patients for whom classic language landmarks are less useful because of reorganization in response to epileptogenic or neoplastic cortex. However, little is known regarding the reliability of the procedure, particularly over extended time intervals. The authors present the case of a young man with refractory left temporal lobe epilepsy in the setting of a low-grade left temporal tumor who had undergone intraoperative language mapping at age 14 years and repeat mapping at age 25. Results from both the initial ESM and the repeat ESM 11 years later revealed a positive auditory description naming site in the same location on the superior temporal gyrus, at the anterior aspect of the tumor. This case provides support for the reliability of ESM and underscores intraindividual reliability in the location of language cortex over a prolonged period.

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.