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Accurate mapping of the seizure onset zone (SOZ) is critical to the success of epilepsy surgery outcomes. Epileptogenicity index (EI) is a statistical method that delineates hyperexcitable brain regions involved in the generation and early propagation of seizures. However, EI can overestimate the SOZ for particular electrographic seizure onset patterns. Therefore, using direct cortical stimulation (DCS) as a probing tool to identify seizure generators, we systematically evaluated the causality of the high EI nodes (>0.3) in replicating the patient's habitual seizures. Specifically, we assessed the diagnostic yield of high EI nodes, i.e., the proportion of high EI nodes that evoked habitual seizures. A retrospective single-center study that included post-stereo encephalography (SEEG) confirmed TLE patients (n = 37) that had all high EI nodes stimulated, intending to induce a seizure. We evaluated the nodal responses (true and false responder rate) to stimulation and correlated with electrographic seizure onset patterns (hypersynchronous-HYP and low amplitude fast activity patterns-LAFA) and clinically defined SOZ. The ictogenicity (i.e., the propensity to induce the patient's habitual seizure) of a high EI node was only 44.5%. The LAFA onset pattern had a significantly higher response rate to DCS (i.e., higher evoked seizures). The concordance of an evoked habitual seizure with a clinically defined SOZ with good outcomes was over 50% (p = 0.0025). These results support targeted mapping of SOZ in LAFA onset patterns by performing DCS in high EI nodes to distinguish seizure generators (true responders) from hyperexcitable nodes that may be involved in early propagation.

Objective Direct cortical stimulation (DCS) is standard for intracranial presurgical evaluation in drug-resistant epilepsy (DRE). Few studies have reported levels of concordance between spontaneous seizure generators and triggered seizures during DCS. The present work reports validity measures of DCS for detecting the seizure onset zone (SOZ) during stereoelectroencephalography (SEEG). Methods We evaluated all patients who underwent SEEG evaluation at our epilepsy center between 2013 and 2019. Data were analyzed using contingency tables. Validity measures of the diagnostic test were computed for all patients evaluated with DCS and for seizure free patients. Results Fifty-eight consecutive patients were evaluated through DCS. One hundred seventy-three clinical seizures were elicited with DCS. Electroclinical identical to spontaneous seizures were considered true positive (TP) seizures. They showed a high specificity (96.9%) for detecting the SOZ in patients that remained seizure free one year after treatment. Sensitivity was low (23.0%), and a high percentage of false-negative stimulations was documented in the SOZ. The accuracy was 87.9%. Conclusions DCS is a technique with high specificity but a low sensitivity for the localization of the SOZ. The DCS validity measures need to be known when considered for surgical decisions. The interpretation of DCS-triggered seizures and the differentiation of true-positive vs false-positive seizures should be carefully evaluated. Significance DCS seizure triggering is highly specific for SOZ localization. This work received support from the project “Clúster Emergent del Cervell Humà” (CECH) and the European Regional Development Fund under the framework of the ERFD Operative Programme for Catalonia.

One of the major challenges during glioblastoma surgery is balancing between maximizing extent of resection and preventing neurological deficits. Several surgical techniques and adjuncts have been developed to help identify eloquent areas both preoperatively (fMRI, nTMS, MEG, DTI) and intraoperatively (imaging (ultrasound, iMRI), electrostimulation (mapping), cerebral perfusion measurements (fUS)), and visualization (5-ALA, fluoresceine)). In this review, we give an update of the state-of-the-art management of both primary and recurrent glioblastomas. We will review the latest surgical advances, challenges, and approaches that define the onco-neurosurgical practice in a contemporary setting and give an overview of the current prospective scientific efforts. ispartof: NEURO-ONCOLOGY PRACTICE vol:9 issue:5 pages:364-379 ispartof: location:England status: published

BACKGROUND Monitoring of motor function during surgery for supratentorial tumors under general anesthesia applies either transcranial electrical stimulation (TES) or direct cortical stimulation (DCS) to elicit motor-evoked potentials. To date, there is no guideline that favor one method over the other. Therefore, we designed this randomized study to compare between both methods regarding the prediction of postoperative motor deficits and extent of tumor resection. METHODS This is a multicenter (six centers in Germany and one in Switzerland), double blind, parallel group, exploratory, randomized controlled clinical trial. Patients without or with mild paresis, who are scheduled for surgical resection of motor-eloquent brain tumors under general anesthesia will be randomized to surgical resection under TES or surgical resection under DCS. The primary endpoint is sensitivity and specificity in prognosis of motor function 7 days after surgery. The main secondary endpoint is the extent of tumor resection. The study is planned to include 120 patients within 2 years. DISCUSSION The present exploratory study should compare TES and DCS regarding sensitivity and specificity in predicting postoperative motor deficit and extent of tumor resection to calculate the required number of patients in a confirmatory trial to test the superiority of one method over the other.

Introduction: Intraoperative neurophysiological monitoring is the golden standard for lesions located in eloquent areas of the brain. On the one hand, positive mapping offers a view of the relationship between the anatomo-functional cortical organisation of the patient and the lesion, facilitating the choice of the cerebrotomy entry point and the resection until the functional borders are found. On the other hand, negative mapping does not offer certainty that the absence of the motor response, from the operative field, is the real feedback or is the result of the false-negative response. In such a situation, a differentiation between those two must be done. Materials and methods: We evaluated the results of direct cortical stimulation of lesion located in or near the primary motor area, which were diagnosticated with contrast-enhancement head MRI and admitted to the Third Department of Neurosurgery, "Prof. Dr N. Oblu” Emergency Clinical Hospital, Iasi, Romania, between January 2014 and July 2018. Special attention was given especially to the negative mapping cases, regarding the histological type, imagistic localisation, symptoms and neurological outcome immediate postoperative, at 6 months and one-year follow-up. Results: From all 66 patients meeting the inclusion and exclusion criteria in 9,09% (6 cases) we did not obtain any motor response after direct cortical stimulation. The imagistic localisations of those cases were: 3 – Rolandic, 2 – pre-Rolandic and one retro-Rolandic. Tumors histological types were: glioblastoma, anaplastic astrocytoma, oligoastrocytoma and oligodendroglioma each one case and two cases of fibrillary astrocytoma. The intensity range was between 6 – 18mA, the mode – 12mA and the median – 10mA. Postoperatively the neurological condition of 3 patients worsened (4,54% from all the cases), while 3 had a favourable evolution with symptom remission. At 6monts and one-year follow-up in one case (1,51%), we observed no improvement in contrast with the other two, where dysfunction remission was highlighted. Conclusion: The possible technical, surgical and anesthesiologic causes of false-negative motor response must be eliminated to be able to differentiate from the real absence of the functional area from the operative field. In the first scenario, the resection may be associated with permanent postoperative neurologic deficit and major life quality alteration while in the second one the patient presents no motor dysfunction after surgery and the resection may be extensive with multiple oncological benefits.

(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.

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.

Objectives. The genesis of tumors is unknown in our days. Surgery represents an effective treatment of this disorder. According to many studies of brain tumor surgery, a motor deficit rate of 30% has been observed, postoperatively, after surgeries on brain tumors in the motor areas. The aim of the study was to evaluate the direct cortical stimulation in the surgical treatment of glial brain tumors, in motor areas. Material and Methods. The examination group included 35 patients with brain tumors, localized in the parasilvian region. Direct cortical stimulation was used intraoperatively, in order to establish the motor areas. For the evaluation of the neurological deficit, a comparative analysis of the pre- and postoperative motor deficit was performed. Results. Direct cortical stimulation was performed in 35 patients. During its stimulation, the motor areas were detected in 32 patients. Under the control of Direct Cortical Stimulation, subtotal and partial tumor resection was performed in 31 patients and, due to the location of the tumor in the motor area, biopsy was performed in 1 patient. The worsening of the postoperative motor deficit was recorded in the partial ablation for 2 patients and biopsy for 1 patient, where the tumor was directly localized in the motor area. Direct cortical stimulation, in the extent of total and subtotal ablation, prevented postoperative motor deficit at discharge in 22 patients. Conclusions. In order to avoid postoperative neurological consequences and improve the patients' quality of life, it is appropriate to use intraoperative direct cortical stimulation.

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.

Objective: We investigated the relationship between the reliability of the transcranial or transcortical motor evoked potential (MEP) response and age in pediatric patients aged ≤15 years with brain tumor. Methods: We retrospectively analyzed the data from 60 consecutive patients aged ≤15 years who had undergone brain tumor surgery that involved intraoperative MEP monitoring from October 2009 to May 2016. Results: A total of 41 patients with reliable signals (MEP response group) and 19 patients without reliable signals (MEP nonresponse group) were included in the present study. The mean age at surgery, body height, and body weight were significantly greater in the MEP response group than in the MEP nonresponse group. When the MEP success rates during surgery of the pediatric population with brain tumors were analyzed in relation to patient age, the transcortical MEP success rate in the 0–5-year age group (10.0%) was significantly lower than that in the 6–10-year age group (71.4%; P = 0.009) and that in the 11–15-year age group (75.0%; P = 0.015). Conclusions: The transcortical MEP response was monitored less successfully during brain tumor surgery in patients aged ≤5 years than in patients aged 6–15 years. Although MEP monitoring techniques can be applied during surgery of pediatric populations with brain tumors similar to that used for adult patients, the limitations of the low transcortical MEP response rate in young patients should be considered., ファイル公開：2019-11-01

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.

The objective of this systematic review is to create an overview of the literature on the comparison of navigated transcranial magnetic stimulation (nTMS) as a mapping tool to the current gold standard, which is (intraoperative) direct cortical stimulation (DCS) mapping. A search in the databases of PubMed, EMBASE, and Web of Science was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and recommendations were used. Thirty-five publications were included in the review, describing a total of 552 patients. All studies concerned either mapping of motor or language function. No comparative data for nTMS and DCS for other neurological functions were found. For motor mapping, the distances between the cortical representation of the different muscle groups identified by nTMS and DCS varied between 2 and 16 mm. Regarding mapping of language function, solely an object naming task was performed in the comparative studies on nTMS and DCS. Sensitivity and specificity ranged from 10 to 100% and 13.3-98%, respectively, when nTMS language mapping was compared with DCS mapping. The positive predictive value (PPV) and negative predictive value (NPV) ranged from 17 to 75% and 57-100% respectively. The available evidence for nTMS as a mapping modality for motor and language function is discussed.

Status epilepticus (SE) is a life-threatening condition with a mortality of up to 60% in the advanced and comatose forms of SE. In one out of five adults, first and second line fails to control epileptic activity, leading to refractory status epilepticus (RSE) and in around 3% to super-refractory status epilepticus (SRSE), where SE continues despite anesthetic treatment for 24 h or more. In this rare but devastating condition, innovative and safe treatments are needed. In a recent review on the use of vagal nerve stimulation in RSE and SRSE, a 74% response rate for abrogation of SE was reported. Here, we review the currently available evidence supporting the use of neurostimulation, including vagal nerve stimulation, direct cortical stimulation, transcranial magnetic stimulation, electroconvulsive therapy, and deep brain stimulation in RSE and SRSE. This article is part of the Special Issue “Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures”.

Background Invasive cortical stimulation (ICS) is a neuromodulation method in which electrodes are implanted on the cortex to deliver chronic stimulation. ICS has been used to treat neurological disorders such as neuropathic pain, epilepsy, movement disorders and tinnitus. Noninvasive neuromodulation methods such as transcranial magnetic stimulation and transcranial electrical stimulation (TES) show great promise in treating some neurological disorders and require no surgery. However, only acute stimulation can be delivered. Epicranial current stimulation (ECS) is a novel concept for delivering chronic neuromodulation through subcutaneous electrodes implanted on the skull. The use of concentric-ring ECS electrodes may allow spatially focused stimulation and offer a less invasive alternative to ICS. Objectives Demonstrate ECS proof-of-concept using concentric-ring electrodes in rats and then use a computational model to explore the feasibility and limitations of ECS in humans. Methods ECS concentric-ring electrodes were implanted in 6 rats and pulsatile stimulation delivered to the motor cortex. An MRI based electro-anatomical human head model was used to explore different ECS concentric-ring electrode designs and these were compared with ICS and TES. Results Concentric-ring ECS electrodes can selectively stimulate the rat motor cortex. The computational model showed that the concentric-ring ECS electrode design can be optimized to achieve focused cortical stimulation. In general, focality was less than ICS but greater than noninvasive transcranial current stimulation. Conclusion ECS could be a promising minimally invasive alternative to ICS. Further work in large animal models and patients is needed to demonstrate feasibility and long-term stability. ispartof: Frontiers in Neuroscience vol:13 ispartof: location:Switzerland status: published

Purpose of Review: This review aims to survey recent trends in electrical forms of neuromodulation, with a specific application to Parkinson’s disease (PD). Emerging trends are identified, highlighting synergies in state-of-the-art neuromodulation strategies, with directions for future improvements in stimulation efficacy suggested. Recent Findings: Deep brain stimulation remains the most common and effective form of electrical stimulation for the treatment of PD. Evidence suggests that transcranial direct current stimulation (tDCS) most likely impacts the motor symptoms of the disease, with the most prominent results relating to rehabilitation. However, utility is limited due to its weak effects and high variability, with medication state a key confound for efficacy level. Recent innovations in transcranial alternating current stimulation (tACS) offer new areas for investigation. Summary: Our understanding of the mechanistic foundations of electrical current stimulation is advancing and as it does so, trends emerge which steer future clinical trials towards greater efficacy.

Transcranial electrical stimulation-motor evoked potential (TES-MEP) is a valuable intraoperative monitoring technique during brain tumor surgery. However, TES can stimulate deep subcortical areas located far from the motor cortex. There is a concern about false-negative results from the use of TES-MEP during resection of those tumors adjacent to the primary motor cortex. Our study reports three cases of TES-MEP monitoring with false-negative results due to deep axonal stimulation during brain tumor resection. Although no significant change in TES-MEP was observed during surgery, study subjects experienced muscle weakness after surgery. Deep axonal stimulation of TES could give false-negative results. Therefore, a combined method of TES-MEP and direct cortical stimulation-motor evoked potential (DCS-MEP) or direct subcortical stimulation should be considered to overcome the limitation of TES-MEP.

Background: Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method: a magnetic field pulse from a TMS coil can excite neurons in a desired location of the cortex. Conventional TMS coils cause focal stimulation underneath the coil centre; to change the location of the stimulated spot, the coil must be moved over the new target. This physical movement is inherently slow, which limits, for example, feedback-controlled stimulation. Objective: To overcome the limitations of physical TMS-coil movement by introducing electronic targeting. Methods: We propose electronic stimulation targeting using a set of large overlapping coils and introduce a matrix-factorisation-based method to design such sets of coils. We built one such device and demonstrated the electronic stimulation targeting in vivo. Results: The demonstrated two-coil transducer allows translating the stimulated spot along a 30-mmlong line segment in the cortex; with five coils, a target can be selected from within a region of the cortex and stimulated in any direction. Thus, far fewer coils are required by our approach than by previously suggested ones, none of which have resulted in practical devices. Conclusion: Already with two coils, we can adjust the location of the induced electric field maximum along one dimension, which is sufficient to study, for example, the primary motor cortex. (C) 2018 The Author(s). Published by Elsevier Inc.

Background : Understanding of cortico-cortical activity in eloquent areas intraoperatively is crucial for neurosurgical procedures. Here, we used intraoperative near-infrared spectroscopy (iNIRS) during direct cortical stimulation as a robust tool to better understand the cortico-cortical connectivity in language systems.Methods : We applied iNIRS to 3 patients who underwent epilepsy surgery due to lesions (cavernous angioma, epidermoid cyst, and low-grade glioma) located in language areas. Using iNIRS, we measured the blood concentration changes of oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR) in the lateral temporal cortex during direct cortical stimulation (50 Hz) at the inferior frontal area where Broca’s area was probabilistically located.Results : In all patients, 50 Hz stimulation elicited hemodynamic changes in the superior temporal gyrus (STG). During 0.8–4.8 s after stimulation, HbO2 increased and HbR decreased in the posterior part of the STG (Wernicke’s area). Similar responses were observed in the anterior part of the STG 1.3–8.0 s after stimulation. Finally, these changes were disappeared in the middle temporal gyrus.Conclusions : Our results suggest that cortical stimulation of Broca’s area elicits hemodynamic responses in Wernicke's area via cortico-cortical connectivity. We demonstrated cortico-cortical evoked responses in language systems using iNIRS during direct cortical stimulation. Our iNIRS data will provide useful information about cortico-cortical networks underlying human brain functions intraoperatively and will contribute to neurosurgical treatment in eloquent areas., 学位の種類: 博士（医学）. 報告番号: 甲第4253号. 学位記番号: 新大院博（医）甲第731号. 学位授与年月日: 平成29年3月23日, Neuroscience Letters 630.136-140,2016, 新大院博（医）甲第731号

Previous non-invasive studies have proposed that the deeply seated region of the medial frontal cortex engages in conflict processing in humans, but its core region has remained to be elucidated. By means of direct cortical stimulation, which excels other techniques in temporal and spatial resolutions and in the capacity of producing transient, functional impairment even in the deeply located cortices, we attempted to obtain direct evidence that the pre-supplementary motor area (pre-SMA) actively engages in conflict processing. Subject was a patient with right frontal lobe epilepsy who underwent invasive presurgical evaluation with subdural electrodes placed on the medial and lateral frontal cortices. During a conflict task – modified Eriksen flanker task, direct cortical stimulation was delivered time-locked to the task at the inferior part of the medial superior frontal gyrus (inferior medial SFG), the superior part of the medial SFG, and the middle frontal gyrus. By adopting the session of sham stimulation that was employed as a within-block control, event-related potentials (ERPs) were recorded from the medial and lateral frontal cortices. The inferior medial SFG showed a significant ERP difference between trials with more and less conflict, while the other frontal cortices did not. Among the three stimulus sites, only stimulation of the inferior medial SFG significantly prolonged reaction time in trials with more conflict. Anatomically, the inferior medial SFG corresponded with the pre-SMA (Brodmann area 8). It was located 1–2 cm rostral to the vertical anterior commissure line where cortical stimulation elicited arrest of motion (the supplementary negative motor area). Functionally, this area corresponded to the dorso-rostral portion of the activation loci in previous neuroimaging studies focusing on conflict processing. By combining epicortical ERP recording and direct cortical stimulation in a human brain, this study, for the first time, presented one direct piece of evidence that the pre-SMA actively participates in conflict processing.

When delivered over a specific cortical site, TMS can temporarily disrupt the ongoing process in that area. This allows mapping of speech-related areas for preoperative evaluation purposes. We numerically explore the observed variability of TMS responses during a speech mapping experiment performed with a neuronavigation system. We selected four cases with very small perturbations in coil position and orientation. In one case (E) a naming error occurred, while in the other cases (NEA, B, C) the subject appointed the images as smoothly as without TMS. A realistic anisotropic head model was constructed of the subject from T1-weighted and diffusion-weighted MRI. The induced electric field distributions were computed, associated to the coil parameters retrieved from the neuronavigation system. Finally, the membrane potentials along relevant white matter fibre tracts, extracted from DTI-based tractography, were computed using a compartmental cable equation. While only minor differences could be noticed between the induced electric field distributions of the four cases, computing the corresponding membrane potentials revealed different subsets of tracts were activated. A single tract was activated for all coil positions. Another tract was only triggered for case E. NEA induced action potentials in 13 tracts, while NEB stimulated 11 tracts and NEC one. The calculated results are certainly sensitive to the coil specifications, demonstrating the observed variability in this study. However, even though a tract connecting Broca's with Wernicke's area is only triggered for the error case, further research is needed on other study cases and on refining the neural model with synapses and network connections. Case-and subject-specific modelling that includes both electromagnetic fields and neuronal activity enables demonstration of the variability in TMS experiments and can capture the interaction with complex neural networks.

Object: Preoperative functional magnetic resonance imaging (fMRI) remains a promising method to aid in the surgical management of patients diagnosed with brain tumors. For patients that are candidates for awake craniotomies, surgical decisions can potentially be improved by fMRI but this depends on the level of concordance between preoperative brain maps and the maps provided by the gold standard intraoperative method, direct cortical stimulation (DCS). There have been numerous studies of the concordance between fMRI and DCS using sensitivity and specificity measures, however the results are variable across studies and the key factors influencing variability are not well understood. Thus, the present work addresses the influence of technical factors on fMRI and DCS concordance. Methods: Motor and language mapping data were collected for a group of glioma patients (n = 14) who underwent both preoperative fMRI and intraoperative DCS in an awake craniotomy procedure for tumor removal. Normative fMRI data were also acquired in a healthy control group (n = 12). The fMRI and DCS mapping data were co-registered; true positive (TP), true negative (TN), false positive (FP), and false negative (FN) occurrences were tabulated over the exposed brain surface. Sensitivity and specificity were measured for the total group, and for the motor and language sub-groups. The influence of grid placement, fMRI statistical thresholding, and task standardization were assessed. Correlations between proportions of agreement and error were also carefully scrutinized to evaluate concordance in more detail. Results: Concordance was significantly better for motor vs. language mapping. There was an inverse relationship between TP and TN with increasing statistical threshold, and FP dominated the total error. Sensitivity and specificity were reduced when tasks were not standardized across fMRI and DCS. Conclusions: Although the agreement between fMRI and DCS is good, variability is introduced by technical factors that can diminish the quality of patient data. Neurosurgeons should evaluate the usefulness of fMRI data while considering that (a) discordance arises primarily from FP fMRI results; (b) there is an inherent trade-off between sensitivity and specificity with fMRI statistical threshold; and (c) best results are achieved using batteries of tasks that are standardized across both mapping methods.

Background 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 patients benefit clinically from preoperative rTMS for language mapping. Methods We enrolled 25 patients with language eloquently located brain lesions undergoing preoperative rTMS language mapping (GROUP 1, 2011–2013), with the mapping results not being available for the surgeon, and we matched these patients with 25 subjects who also underwent preoperative rTMS (GROUP 2, 2013–2014), but the mapping results were taken into account during tumor resection. Additionally, cortical language maps were generated by analyzing preoperative rTMS and intraoperative direct cortical stimulation (DCS) data. Results Mean anterior-posterior (ap) craniotomy extents and overall craniotomy sizes were significantly smaller for the patients in GROUP 2 (Ap: p = 0.0117; overall size: p = 0.0373), and postoperative language deficits were found significantly more frequently for the patients in GROUP 1 (p = 0.0153), although the preoperative language status did not differ between groups (p = 0.7576). Additionally, there was a trend towards fewer unexpected tumor residuals, shorter surgery duration, less peri- or postoperative complications, shorter inpatient stay, and higher postoperative Karnofsky performance status scale (KPS) for the patients in GROUP 2. Conclusions The present study provides a first hint that the clinical course of patients suffering from brain tumors might be improved by preoperative rTMS language mapping. However, a significant difference between both groups was only found for craniotomy extents and postoperative deficits, but not for other clinical parameters, which only showed a trend toward better results in GROUP 2. Therefore, multicenter trials with higher sample sizes are needed to further investigate the distinct impact of rTMS language mapping on the clinical course of brain tumor patients.

Transcranial magnetic stimulation (TMS) has been used to induce speech disturbances and to affect speech performance during different naming tasks. Lately, repetitive navigated TMS (nTMS) has been used for non-invasive mapping of cortical speech-related areas. Different naming tasks may give different information that can be useful for presurgical evaluation. We studied the sensitivity of object and action naming tasks to nTMS and compared the distributions of cortical sites where nTMS produced naming errors. Eight healthy subjects named pictures of objects and actions during repetitive nTMS delivered to semi-random left-hemispheric sites. Subject-validated image stacks were obtained in the baseline naming of all pictures before nTMS. Thereafter, nTMS pulse trains were delivered while the subjects were naming the images of objects or actions. The sessions were video-recorded for offline analysis. Naming during nTMS was compared with the baseline performance. The nTMS-induced naming errors were categorized by error type and location. nTMS produced no-response errors, phonological paraphasias, and semantic paraphasias. In seven out of eight subjects, nTMS produced more errors during object than action naming. Both intrasubject and intersubject analysis showed that object naming was significantly more sensitive to nTMS. When the number of errors was compared according to a given area, nTMS to postcentral gyrus induced more errors during object than action naming. Object naming is apparently more easily disrupted by TMS than action naming. Different stimulus types can be useful for locating different aspects of speech functions. This provides new possibilities in both basic and clinical research of cortical speech representations.

ObjectiveLesion-based mapping of speech pathways has been possible only during invasive neurosurgical procedures using direct cortical stimulation (DCS). However, navigated transcranial magnetic stimulation (nTMS) may allow for lesion-based interrogation of language pathways noninvasively. Although not lesion-based, magnetoencephalographic imaging (MEGI) is another noninvasive modality for language mapping. In this study, we compare the accuracy of nTMS and MEGI with DCS.MethodsSubjects with lesions around cortical language areas underwent preoperative nTMS and MEGI for language mapping. nTMS maps were generated using a repetitive TMS protocol to deliver trains of stimulations during a picture naming task. MEGI activation maps were derived from adaptive spatial filtering of beta-band power decreases prior to overt speech during picture naming and verb generation tasks. The subjects subsequently underwent awake language mapping via intraoperative DCS. The language maps obtained from each of the 3 modalities were recorded and compared.ResultsnTMS and MEGI were performed on 12 subjects. nTMS yielded 21 positive language disruption sites (11 speech arrest, 5 anomia, and 5 other) while DCS yielded 10 positive sites (2 speech arrest, 5 anomia, and 3 other). MEGI isolated 32 sites of peak activation with language tasks. Positive language sites were most commonly found in the pars opercularis for all three modalities. In 9 instances the positive DCS site corresponded to a positive nTMS site, while in 1 instance it did not. In 4 instances, a positive nTMS site corresponded to a negative DCS site, while 169 instances of negative nTMS and DCS were recorded. The sensitivity of nTMS was therefore 90%, specificity was 98%, the positive predictive value was 69% and the negative predictive value was 99% as compared with intraoperative DCS. MEGI language sites for verb generation and object naming correlated with nTMS sites in 5 subjects, and with DCS sites in 2 subjects.ConclusionMaps of language function generated with nTMS correlate well with those generated by DCS. Negative nTMS mapping also correlates with negative DCS mapping. In our study, MEGI lacks the same level of correlation with intraoperative mapping; nevertheless it provides useful adjunct information in some cases. nTMS may offer a lesion-based method for noninvasively interrogating language pathways and be valuable in managing patients with peri-eloquent lesions.

Background: Transcranial electric stimulation as used during intraoperative neurostimulation is dependent on electrode and skull impedances.Objective: Threshold currents, voltages and electrode impedances were evaluated with electrical stimulation at 8 successive layers between the skin and the cerebral cortex.Patients and Methods: Data of 10 patients (6f, 53 +/- 11 years) were analyzed. Motor evoked potentials were elicited by constant current stimulation with corkscrew type electrodes (CS) at C3 and C4 in line with standard transcranial electric stimulation. A monopolar anodal ball tip shaped probe was used for all other measurements being performed at the level of the skin, dura and cortex, as well as within the skull by stepwise performed burr holes close to C3 resp. C4.Results: Average stimulation intensity, corresponding voltage and impedance for muscle MEPs at current motor threshold (CMT) were recorded: CS 54 +/- 23 mA (mean +/- SD), 38 +/- 21 V. 686 +/- 146 Omega; with the monopolar probe on skin 55 +/- 28 mA, 100 +/- 44 V. 1911 +/- 683 Omega and scalp 59 +/- 32 mA, 56 +/- 28 V. 1010 +/- 402 Omega; within the skull bone: outer compact layer 33 23 mA, 91 +/- 53 V. 3734 +/- 2793 Omega; spongiform layer 33 +/- 23 mA, 70 +/- 44 V.2347 +/- 1327 Omega; inner compact layer (ICL) 28 +/- 19 mA, 48 +/- 23 V. 2103 +/- 14980; on dura 25 +/- 12 mA, 17 +/- 12 V.643 +/- 244 Omega and cortex 14 +/- 6 mA, 11 +/- 5 V.859 +/- 300 Omega. CMTs were only significantly different for CS (P = 0.02) and for the monopolar probe between the cortex and ICL (P = 0.03), scalp (P = 0.01) or skin (P = 0.01) and between ICL and CS (PConclusion: The mean stimulation current of the CMT along the extracranial to intracranial anodal trajectory followed a stepwise reduction. VMT was strongly dependent on electrode impedance. CMT within the skull layers was noted to have relative strong shunting currents in scalp layers. (C) 2013 Elsevier Inc. All rights reserved.

Modern neurosurgery attempts to get the difficult goal of combining an "aggressive" resection of brain tumors with the fundamental purpose of preserving brain functions and best possible quality of life. One of the most important evolutions of neurosurgical therapies is the opportunity to provide a customized surgical intervention by using modern methods to "map" the eloquent areas of the brain. This allows the identification of brain functional areas to be preserved from possible inadvertent intraoperative damage. Direct cortical stimulation (DCS) is an intraoperative technique that uses electrodes placed directly on the exposed cortical surface of the brain to stimulate activity of functional areas by simultaneously recording the evoked responses peripherally. DCS is very precise and reliable and can be considered the gold standard in brain mapping and intraoperative functional monitoring. Nevertheless, the neurosurgeon discovers the spatial relationship between the disease and eloquent cortical surfaces only after having completed a craniotomy and dural opening. A pre-surgical mapping method would give the opportunity to plan the treatment of brain diseases optimizing many aspects of the surgical treatment, including patient positioning, type of anesthesia, size of craniotomy, and extent of resection. Moreover, pre-surgical mapping would allow more precise prediction of the efficacy and risks of treatments that can be discussed with the patient and influence the therapeutic strategy. New techniques have been proposed in an attempt to provide a reliable method for the functional study that can be, however, exploited pre-operatively. The most recent of these methods of mapping cortical activities is navigated brain stimulation (NBS), which is based on the neurophysiological technique of transcranial magnetic stimulation (TMS) of the cerebral cortex combined with the conventional neuronavigation. Basic principles of NBS will be here discussed together with our preliminary experience using this technique in different neurosurgical diseases.

Object Direct cortical stimulation (DCS) is the gold-standard technique for motor mapping during craniotomy. However, preoperative noninvasive motor mapping is becoming increasingly accurate. Two such noninvasive modalities are navigated transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) imaging. While MEG imaging has already been extensively validated as an accurate modality of noninvasive motor mapping, TMS is less well studied. In this study, the authors compared the accuracy of TMS to both DCS and MEG imaging. Methods Patients with tumors in proximity to primary motor cortex underwent preoperative TMS and MEG imaging for motor mapping. The patients subsequently underwent motor mapping via intraoperative DCS. The loci of maximal response were recorded from each modality and compared. Motor strength was assessed at 3 months postoperatively. Results Transcranial magnetic stimulation and MEG imaging were performed on 24 patients. Intraoperative DCS yielded 8 positive motor sites in 5 patients. The median distance ± SEM between TMS and DCS motor sites was 2.13 ± 0.29 mm, and between TMS and MEG imaging motor sites was 4.71 ± 1.08 mm. In no patients did DCS motor mapping reveal a motor site that was unrecognized by TMS. Three of 24 patients developed new, early neurological deficit in the form of upper-extremity paresis. At the 3-month follow-up evaluation, 2 of these patients were significantly improved, experiencing difficulty only with fine motor tasks; the remaining patient had improvement to 4/5 strength. There were no deaths over the course of the study. Conclusions Maps of the motor system generated with TMS correlate well with those generated by both MEG imaging and DCS. Negative TMS mapping also correlates with negative DCS mapping. Navigated TMS is an accurate modality for noninvasively generating preoperative motor maps.

OBJECTIVE: Language functional magnetic resonance imaging (fMRI) has been used extensively in the past decade for both clinical and research purposes. Its integration in the preoperative imaging assessment of brain lesions involving eloquent areas is progressively more diffused in neurosurgical practice. Nevertheless, the reliability of language fMRI is unclear. To understand the reliability of preoperative language fMRI in patients operated on for brain tumors, the surgical studies that compared language fMRI with direct cortical stimulation (DCS) were reviewed. METHODS: Articles comparing language fMRI with DCS of language areas were reviewed with attention to the lesion pathology, the magnetic field, the language tasks used pre- and intraoperatively, and the validation modalities adopted to establish the reliability of language fMRI. We tried to explore the effectiveness of language fMRI in gliomas. RESULTS: Nine language brain mapping studies compared the findings of fMRI with those of DCS. The studies are not homogeneous for tumor types, magnetic fields, pre- and intraoperative language tasks, intraoperative matching criteria, and results. Sensitivity and specificity were calculated in 5 studies (respectively ranging from 59% to 100% and from 0% to 97%). CONCLUSION: The contradictory results of these studies do not allow consideration of language fMRI as an alternative tool to DCS in brain lesions located in language areas, especially in gliomas because of the pattern of growth of these tumors. However, language fMRI conducted with high magnet fields is a promising brain mapping tool that must be validated by DCS in methodological robust studies. Copyright © 2010 by the Congress of Neurological Surgeons

There is increasing evidence that the extent of tumor removal in low-grade glioma surgery is related to patient survival time. Thus, the goal of resecting the largest amount of tumor possible without leading to permanent neurological sequelae is a challenge for the neurosurgeon. Electrical stimulation of the brain to detect cortical and axonal areas involved in motor, language, and cognitive function and located within the tumor or along its boundaries has become an essential tool in combination with awake craniotomy. Based on a literature review, discussions within the European Low-Grade Glioma Group, and illustrative clinical experience, the authors of this paper provide an overview for neurosurgeons, neurophysiologists, linguists, and anesthesiologists as well as those new to the field about the stimulation techniques currently being used for mapping sensorimotor, language, and cognitive function in awake surgery for low-grade glioma. The paper is intended to help the understanding of these techniques and facilitate a comparison of results between users.