Intraoperative Direct Cortical Stimulation Research Articles

P025 Resection of highly language-eloquent brain lesions purely based on rTMS language mapping without awake surgery

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

Probing parietal-motor connectivity by means of intraoperative direct cortical stimulation

Probing parietal-motor connectivity by means of intraoperative direct cortical stimulation

9. Navigated transcranial magnetic stimulation (nTMS) for preoperative mapping in motor areas tumor surgery: Comparison with functional magnetic resonance imaging (fMRI) and intraoperative direct cortical stimulation

Navigated transcranial magnetic stimulation (nTMS) is a novel technology in the field of neurosurgery for noninvasive delineation of cortical functional topography. Recent studies show that it can detect eloquent cortical areas directly, comparable to intraoperative direct cortical stimulation (DCS). The aim of this study was to evaluate the nTMS in comparison with functional magnetic resonance imaging (fMRI) in the setting of brain tumors involving motor areas. Thirteen consecutive patients affected by frontal lobe brain tumors were enrolled in the study. All patients received an fMRI and nTMS examination preoperatively. Consistency of preoperative mapping with intraoperative DCS was assessed off-line by means of the neuronavigation system: as result, nTMS produced statistically significant higher accuracy scores of the motor area localization than fMRI. Moreover, nTMS has fewer restrictions for preoperative functional mapping than fMRI and requires only a limited level of compliance: so it represents an useful and reliable technique during preoperative planning for surgical decision making in the clinical setting.

Sources of Variation Influencing Concordance between Functional MRI and Direct Cortical Stimulation in Brain Tumor Surgery.

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.

PS2 - 196 Investigating the Spatial Agreement Between Pre-Operative Functional MRI and Intra-Operative Direct Cortical Stimulation

Pre-operative functional magnetic resonance imaging (fMRI) has emerged as valuable clinical tool to help surgically manage patients diagnosed with brain tumours. Surgical decision-making may be significantly improved through the provision of fMRI, however its clinical usage is contingent on the level of agreement with direct cortical stimulation (DCS). While previous studies have been undertaken to investigate the spatial agreement between fMRI and DCS, the influence that various factors may have on fMRI sensitivity and specificity is not fully clear. Thus, in a group of eight brain tumour patients who underwent pre-operative fMRI followed intra-operative DCS during an awake craniotomy procedure, we measured the agreement between the two brain mapping techniques looking at the influence of behavioural task, statistical threshold, and task standardization. Results: There were significant differences between motor and language mapping, where agreement was better for the former. Sensitivity and specificity shared an inverse relationship with increasing fMRI threshold, and were significantly reduced in the case where tasks were not standardized. Lastly, false positive occurrences were identified as the dominate source of error in comparison to false negative occurrences. Conclusion: Thus, the results from this work suggest that fMRI can predict intraoperative findings with good accuracy, however, sources of variability may significantly reduce the quality of fMRI data at the single-subject level. Neurosurgeons should carefully evaluate fMRI data with these considerations prior to its inclusion in the surgical-decision making process.

Resection of highly language-eloquent brain lesions based purely on rTMS language mapping without awake surgery.

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

EP 133. Structural connectivity of eloquent speech areas defined by direct cortical stimulation mapping

The anatomical borders of eloquent speech areas, e.g. Broca’s area, have been vaguely defined and exhibit high inter-subject variability (Amunts and Zilles, 2012), mainly due to inconsistent morphology of the inferior frontal gyrus (IFG) (Ebeling et al., 1989) and small-scale incongruity of functional segregation with respect to anatomical landmarks (Garrett et al., 2012, Quiñones-Hinojosa et al., 2003). However, knowing the exact boundaries of the eloquent cortex became clinically important in preventing postoperative deficits after brain surgery (Garrett et al., 2012, Hollon et al., 2015). The awake electrical stimulation mapping (ESM) has become the preferred method to delineate the speech cortex, as the current non-invasive alternatives lack specificity and spatial resolution (Garrett et al., 2012, Hollon et al., 2015). Since the structural connectivity-based parcellation using diffusion tensor imaging (DTI) has been shown to closely relate to the cytoarchitectonics in the IFG (Klein et al., 2007), we tested whether the location of eloquent cortex could be better predicted by preoperative DTI rather than by its relation to gyrification. Seventeen patients (8 males, median age 33, range 18–63) suffering from primary brain tumor underwent pre-operative 3T MRI scanning using a high resolution T1 MPRAGE and a single shell diffusion weighted imaging (DWI) sequence (60 directions, b = 1000 s/mm2, resolution 2 × 2 × 2 mm), and intraoperative direct cortical electrical stimulation with a bipolar Ojemann electrode during awake language mapping. After standard preprocessing, probabilistic fiber tracking (PROBTRACKX in FSL (Behrens et al., 2007)) was carried out using 5 mm spheres as cortico-subcortical seeds placed at the intraoperatively defined positive stimulation sites. The resulting cortical projections were then overlaid onto the individual cortex surface (Freesurfer) and compared visually and using binary logical operations. A variety of stimulation-positive functional sites was detected, producing anomia, counting, speech and motor arrest. Anomia sites were found both in the pars triangularis and pars opercularis of the inferior frontal gyrus (also in individual patients). Even opercular anomia sites followed the connectivity pattern of triangular anomia sites and had stronger connections to the rostral parts of the mesial prefrontal cortex and pre-supplementary motor area (pre-SMA) than to the precentral gyrus and SMA proper, as opposed to opercular speech or counting arrest sites which also connected more strongly to more posterior parts of the brain, mostly posterior temporal cortex. Thus, even adjacent sites on the same gyrus that differed in function showed dissociable structural connectivity. Our results suggest that structure–function relationships are more evident between function and structural connectivity than between function and gyrification. This study was supported by the German Research Foundation, the European Union, and the German Academic Exchange Service (DAAD).

EP 22. A sleep surgery of language eloquent brain lesions purely based on rTMS language mapping

Objective The resection of left-sided perisylvian brain lesions harbors the risk of postoperative language impairment. Hence, neurosurgeons determine the individual patient’s language distribution by using intraoperative direct cortical stimulation (DCS) during awake surgery. Yet, not all patients qualify for awake surgery. Since non-invasive language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) has frequently shown a high correlation in comparison with the results of DCS language mapping in terms of language-negative brain regions, the present study analyzes oncological and functional outcome of patients who underwent left-sided perisylvian resection of brain lesions purely based on the results of rTMS language mapping. Methods Four patients (astrocytoma WHO grade III of the superior temporal gyrus, astrocytoma WHO grade III of the middle and inferior temporal gyrus, glioblastoma WHO IV of the opercular part of the frontal gyrus, and cavernoma of the insular lobe) underwent rTMS language mapping prior to surgery and data of rTMS language mapping were transferred to the intraoperative neuronavigation system. Preoperatively, 5 days after surgery (=POD5), and 3 months after surgery (=POM3) clinical follow-up was performed. Results No patient suffered from a new surgery-related aphasia. Three patients underwent complete resection immediately, while one patient required a second resection some days later. Conclusion Despite only presenting 4 patients, we could show the feasibility of successfully resecting language-eloquent brain lesions purely based on rTMS language mapping data as a rescue strategy in selected cases in which awake surgery is impossible. No patient was harmed and the extent of resection was oncologically optimal.

FV 3. Higher concordance of navigated transcranial magnetic stimulation (nTMS) than of functional MRI with intraoperative direct cortical stimulation (DCS) for delineating the primary motor area

Objective To optimize the outcome after brain tumour surgery not only with regard to completeness of resection but also to postoperative motor functions and, thus, quality of life, individual assessment of the surgery-related functional risk is mandatory. Therefore, navigated transcranial magnetic stimulation (nTMS) has been used more and more as a reasonable alternative to functional magnetic resonance imaging (fMRI) over the last years. We compared the congruency of nTMS vs. fMRI results for non-invasively mapping the primary motor cortex (M1) prior to surgery with the gold standard method of direct cortical simulation (DCS). Methods 32 patients with intracerebral tumours underwent nTMS and fMRI prior to surgery. The cortical hotspots (HS) and Centres of Gravity (CoG) of M1 of the hand, the foot and the tongue representation were determined for each localizer technique and controlled by DCS. Euclidean distances (ED) between nTMS/fMRI and the respective DCS HS/CoG’s were computed in 3D. Moreover, nTMS, fMRI and DCS maps were projected onto the cortical surface following normalization to a standard brain. After smoothing, overlap volumes between both nTMS and fMRI with DCS functional maps (voxels) were calculated. Results CoG’s of the nTMS maps were located significantly closer to the respective DCS CoG’s as compared to fMRI ( p ± 6.0/17.3 ± 9.6 mm) and the foot (nTMS-DCS/fMRI-DCS: 16.2 ± 20/21.7 ± 17 mm) representation. However, comparison of hotspots did not reveal statistically significant differences. Regarding the overlap of entire functional maps, nTMS showed a higher agreement with DCS as compared to fMRI ( p ± 17%/57 ± 34%; p Conclusions Comparison of both M1 CoG’s and volume overlaps suggest that nTMS agrees better with the gold standard of intraoperative DCS as compared to fMRI, especially regarding the hand and the foot representation and, thus, is recommendable for presurgical M1 mapping. However, both methods should be regarded as complementary, particularly in respect of the tongue representation which is less easy to depict by nTMS.

The impact of preoperative language mapping by repetitive navigated transcranial magnetic stimulation on the clinical course of brain tumor patients.

BackgroundLanguage 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.MethodsWe 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.ResultsMean 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.ConclusionsThe 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.

Comparison of navigated transcranial magnetic stimulation and functional magnetic resonance imaging for preoperative motor mapping in cortical motor areas surgery

Intraoperative direct cortical stimulation (DCS) is considered the gold standard method for neurosurgical motor mapping in rolandic tumor surgery. The most commonly used toll for preoperative localization of motor areas is the functional magnetic resonance imaging (fMRI). Navigated transcranial magnetic stimulation (nTMS) is a new tool for preoperative detection of motor cortical areas.

34. Structural connectivity of eloquent speech areas defined by direct cortical stimulation mapping

Background and aims The anatomical borders of eloquent speech areas, e.g. Broca's area, have been vaguely defined and exhibit high inter-subject variability (Amunts and Zilles, 2012), mainly due to inconsistent morphology of the inferior frontal gyrus (IFG) (Ebeling et al., 1989) and small-scale incongruity of functional segregation with respect to anatomical landmarks (Garrett et al., 2012; Quinones-Hinojosa et al., 2003). However, knowing the exact boundaries of the eloquent cortex became clinically important in preventing postoperative deficits after brain surgery (Garrett et al., 2012; Hollon et al., 2015). The awake electrical stimulation mapping (ESM) has become the preferred method to delineate the speech cortex, as the current non-invasive alternatives lack specificity and spatial resolution (Garrett et al., 2012; Hollon et al., 2015). Since the structural connectivity-based parcellation using diffusion tensor imaging (DTI) has been shown to closely relate to the cytoarchitectonics in the IFG (Klein et al., 2007), we tested whether the location of eloquent cortex could be better predicted by preoperative DTI rather than by its relation to gyrification. Methods Seventeen patients (8 males, median age 33, range 18–63) suffering from primary brain tumor underwent pre-operative 3T MRI scanning using a high resolution T1 MPRAGE and a single shell diffusion weighted imaging (DWI) sequence (60 directions, b =1000 s/mm 2 , resolution 2×2×2mm), and intraoperative direct cortical electrical stimulation with a bipolar Ojemann electrode during awake language mapping. After standard preprocessing, probabilistic fiber tracking (PROBTRACKX in FSL (Behrens et al., 2007)) was carried out using 5mm spheres as cortico-subcortical seeds placed at the intraoperatively defined positive stimulation sites. The resulting cortical projections were then overlaid onto the individual cortex surface (Freesurfer) and compared visually and using binary logical operations. Results A variety of stimulation-positive functional sites was detected, producing anomia, counting, speech and motor arrest. Anomia sites were found both in the pars triangularis and pars opercularis of the inferior frontal gyrus (also in individual patients). Even opercular anomia sites followed the connectivity pattern of triangular anomia sites and had stronger connections to the rostral parts of the mesial prefrontal cortex and pre-supplementary motor area (pre-SMA) than to the precentral gyrus and SMA proper, as opposed to opercular speech or counting arrest sites which also connected more strongly to more posterior parts of the brain, mostly posterior temporal cortex. Thus, even adjacent sites on the same gyrus that differed in function showed dissociable structural connectivity. Conclusions Our results suggest that structure–function relationships are more evident between function and structural connectivity than between function and gyrification. Acknowledgement This study was supported by the German Research Foundation, the European Union, and the German Academic Exchange Service (DAAD).

Structural connectivity of left cortical speech regions defined by direct cortical stimulation during awake language mapping

Event Abstract Back to Event Structural connectivity of left cortical speech regions defined by direct cortical stimulation during awake language mapping Christian Kell1*, Pavel Hok2, Silke Fuhrmann1, Ines Kropff3, Marie-Therese Forster3, Christian Senft3 and Volker Seifert3 1 Goethe University, Department of Neurology, Germany 2 Palacky University, Department of Neurology, Czechia 3 Goethe University, Department of Neurosurgery, Germany The location of eloquent cortex is highly variable. Left hemispheric surgery thus requires functional language mapping via intraoperative direct cortical electric stimulation during neuropsychological testing, which provides a detailed functional map of regions that are critically involved in the tested task. Although the patient's brains are abnormal due to mass lesions, these results provide nevertheless insights into general Neurophysiological principles. We previously could not find a clear relationship between individual regions involved in articulation, speech planning and picture naming and individual gyrification. To test whether the lack of clear attributable functional roles of individual gyri was related to different structural connectivity, we obtained pre-operative T1 and DWI datasets (3T, 60 dir) in so far 4 patients and performed probabilistic fiber tracking (FDT in FSL) using 5mm spheres around the functionally positive sites as seeds, yielding posterior probability distribution maps thresholded at the 90th percentile of all non-zero values. Independent of individual function, the triangular inferior frontal gyrus (IFG) projected to more rostral parts of the mesial prefrontal cortex (mPFC) compared to the opercular IFG that projected to the more caudal pre-SMA and lateral articulatory motor cortex (M1). Yet, independently from individual location on a given gyrus, anomia sites projected to the mPFC and locally to the opercular IFG. Speech arrest sites had local projections to frontal operculum, M1 and postcentral gyrus but also long-range connections to the dorsal premotor cortex, pre-SMA and via the arcuate fascicle to the posterior middle temporal gyrus. Even adjacent sites on the same gyrus that differed in function showed dissociable structural connectivity. Our results suggest that structure-function relationships are more evident between function and structural connectivity than between function and gyrification. This implies a developmental dissociation between gyrification and functional specialization. Keywords: direct cortical stimulation, structural connectivity, Language mapping, awake brain tumor surgery, probabilistic fiber tracking Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Language Citation: Kell C, Hok P, Fuhrmann S, Kropff I, Forster M, Senft C and Seifert V (2015). Structural connectivity of left cortical speech regions defined by direct cortical stimulation during awake language mapping. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00213 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Dr. Christian Kell, Goethe University, Department of Neurology, Frankfurt, Germany, c.kell@em.uni-frankfurt.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Christian Kell Pavel Hok Silke Fuhrmann Ines Kropff Marie-Therese Forster Christian Senft Volker Seifert Google Christian Kell Pavel Hok Silke Fuhrmann Ines Kropff Marie-Therese Forster Christian Senft Volker Seifert Google Scholar Christian Kell Pavel Hok Silke Fuhrmann Ines Kropff Marie-Therese Forster Christian Senft Volker Seifert PubMed Christian Kell Pavel Hok Silke Fuhrmann Ines Kropff Marie-Therese Forster Christian Senft Volker Seifert Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The evolution of brain surgery on awake patients.

In the early days of modern neurological surgery, the inconveniences and potential dangers of general anesthesia by chloroform and ether using the so-called "open-drop technique" led to the quest for alternative methods of anesthesia. Besides preventing the feared side effects, the introduction of regional anesthesia revealed another decisive advantage over general anesthesia in neurosurgery: While intraoperative direct cortical stimulation under general anesthesia could only delineate the motor area (by evocation of contralateral muscular contraction), now, the awake patients were able to report sensations elicited by this method. These properties advanced regional anesthesia to the regimen of choice for cranial surgeries in the first half of the 20th century. While technical advances and new drugs led to a progressive return to general anesthesia for neurosurgical procedures, the use of regional anesthesia for epilepsy surgery has only decreased in recent decades. Meanwhile, awake craniotomies regained popularity in oncologically motivated surgeries, especially in craniotomies for diffuse low-grade gliomas. Intraoperative mapping of brain functions using electrical stimulation in awake patients enables not only for increased tumor removal while preserving the functional status of the patients but also opens a window to cognitive neuroscience. Observations during such interventions and their correlation with both pre - and postoperative neuropsychological examinations and functional neuroimaging is progressively leading to new insights into the complex functional anatomy of the human brain. Furthermore, it broadens our knowledge on cerebral network reorganization in the presence of disease-with implications for all disciplines of clinical neuroscience.

Optimal timing of pulse onset for language mapping with navigated repetitive transcranial magnetic stimulation

ObjectWithin the primary motor cortex, navigated transcranial magnetic stimulation (nTMS) has been shown to yield maps strongly correlated with those generated by direct cortical stimulation (DCS). However, the stimulation parameters for repetitive nTMS (rTMS)-based language mapping are still being refined. For this purpose, the present study compares two rTMS protocols, which differ in the timing of pulse train onset relative to picture presentation onset during object naming. Results were the correlated with DCS language mapping during awake surgery. MethodsThirty-two patients with left-sided perisylvian tumors were examined by rTMS prior to awake surgery. Twenty patients underwent rTMS pulse trains starting at 300ms after picture presentation onset (DELAYED TMS), whereas another 12 patients received rTMS pulse trains starting at the picture presentation onset (ONSET TMS). These rTMS results were then evaluated for correlation with intraoperative DCS results as gold standard in terms of differential consistencies in receiver operating characteristics (ROC) statistics. Logistic regression analysis by protocols and brain regions were conducted. ResultsWithin and around Broca's area, there was no difference in sensitivity (ONSET TMS: 100%, DELAYED TMS: 100%), negative predictive value (NPV) (ONSET TMS: 100%, DELAYED TMS: 100%), and positive predictive value (PPV) (ONSET TMS: 55%, DELAYED TMS: 54%) between the two protocols compared to DCS. However, specificity differed significantly (ONSET TMS: 67%, DELAYED TMS: 28%). In contrast, for posterior language regions, such as supramarginal gyrus, angular gyrus, and posterior superior temporal gyrus, early pulse train onset stimulation showed greater specificity (ONSET TMS: 92%, DELAYED TMS: 20%), NPV (ONSET TMS: 92%, DELAYED TMS: 57%) and PPV (ONSET TMS: 75%, DELAYED TMS: 30%) with comparable sensitivity (ONSET TMS: 75%, DELAYED TMS: 70%). Logistic regression analysis also confirmed the greater fit of the predictions by rTMS that had the pulse train onset coincident with the picture presentation onset when compared to the delayed stimulation. Analyses of differential disruption patterns of mapped cortical regions were further able to distinguish clusters of cortical regions standardly associated with semantic and pre-vocalization phonological networks proposed in various models of word production. Repetitive nTMS predictions by both protocols correlate well with DCS outcomes especially in Broca's region, particularly with regard to TMS negative predictions. ConclusionsWith this study, we have demonstrated that rTMS stimulation onset coincident with picture presentation onset improves the accuracy of preoperative language maps, particularly within posterior language areas.Moreover, immediate and delayed pulse train onsets may have complementary disruption patterns that could differentially capture cortical regions causally necessary for semantic and pre-vocalization phonological networks.

Repeated mapping of cortical language sites by preoperative navigated transcranial magnetic stimulation compared to repeated intraoperative DCS mapping in awake craniotomy

BackgroundRepetitive navigated transcranial magnetic stimulation (rTMS) was recently described for mapping of human language areas. However, its capability of detecting language plasticity in brain tumor patients was not proven up to now. Thus, this study was designed to evaluate such data in order to compare rTMS language mapping to language mapping during repeated awake surgery during follow-up in patients suffering from language-eloquent gliomas.MethodsThree right-handed patients with left-sided gliomas (2 opercular glioblastomas, 1 astrocytoma WHO grade III of the angular gyrus) underwent preoperative language mapping by rTMS as well as intraoperative language mapping provided via direct cortical stimulation (DCS) for initial as well as for repeated Resection 7, 10, and 15 months later.ResultsOverall, preoperative rTMS was able to elicit clear language errors in all mappings. A good correlation between initial rTMS and DCS results was observed. As a consequence of brain plasticity, initial DCS and rTMS findings only corresponded with the results obtained during the second examination in one out of three patients thus suggesting changes of language organization in two of our three patients.ConclusionsThis report points out the usefulness but also the limitations of preoperative rTMS language mapping to detect plastic changes in language function or for long-term follow-up prior to DCS even in recurrent gliomas. However, DCS still has to be regarded as gold standard.

The value of preoperative fMRI in drawing attention to possible unexpected language area representations in a patient with anaplastic astrocytoma

This is a case study of a right handed patient with a/INS; grade III /INS;anaplastic astrocytoma in the superior frontal cortex with intra-axial extensions to the corpus callosum. Presurgical functional MR imaging (fMRI) was done to visualize language network distribution. Intraoperative direct cortical stimulation (DCS) was accordingly done to prevent eloquent functional regions from resection. fMRI results showed a distributed language network including the left inferior frontal gyrus (pars opercularis), the left and right frontal orbital cortices, the left insular cortex, the left superior and middle temporal gyri, the left precentral and postcentral gyri, and the supplementary area.

Language mapping with navigated repetitive TMS: Proof of technique and validation

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.

Introduction: Functional imaging

The evolution of neurosurgery has in many ways paralleled the evolution of technology used to image the nervous system. It is no exaggeration to say that safe and effective modern neurosurgery has largely been made possible by advances in structural neuroimaging that permit evermore precise delineation of normal and abnormal anatomy in the brain and spine. Within the last 2 decades, and in particular since the turn of the century, structural imaging is increasingly being complemented by imaging approaches that allow the neurosurgeon to observe and measure neural activity and connectivity. These functional imaging techniques span multiple modalities and can assist the neurosurgeon in diagnosing neurosurgical conditions, selecting appropriate patients for neurosurgical intervention, performing preoperative and intraoperative brain mapping to avoid damage to eloquent areas of the brain during surgery, and assessing neuroplasticity during postsurgical recovery. In effect, the marriage of structural and functional imaging is ushering in a new era of neurosurgical practice that could be called—to borrow terminology from the technology world—Neurosurgery 2.0. It is, of course, impossible to cover all neurosurgically relevant aspects of functional imaging in a single issue of Neurosurgical Focus. Our aim is simply to provide an effective introduction to several functional imaging approaches in the neurosurgical armamentarium. The articles are ordered in such a way as to take the reader from current and established applications of functional imaging to emerging applications to exciting preclinical work with translational potential. We begin with a review by Abdullah et al. summarizing the published literature on diffusion tensor imaging (DTI) as an adjunct to the resection of gliomas. In many centers, DTI acquisition is now a routine component of preoperative MRI in patients with brain tumors, and DT images are widely used for planning the surgical approach and during intraoperative neuronavigation. This paper is followed by a review on functional imaging in the setting of intracerebral hemorrhage by McDowell et al., which emphasizes its role in assessing the evolution, prognosis, and pathophysiology of this common neurosurgical condition. Takahashi et al. introduce the technique of navigated transcranial magnetic stimulation (nTMS), and they review its application to presurgical motor mapping in patients with perirolandic brain tumors. By critically assessing 11 published series in which nTMS mapping was performed, the authors show that the accuracy of nTMS for motor mapping compares favorably with both intraoperative direct cortical stimulation and functional MRI (fMRI). The next 2 papers represent single-institution experiences with selected applications of functional imaging to specific neurosurgical disorders. Sommer et al. pre sent a sizable series of patients with lesional extratemporal epilepsy in whom resection was guided by integrated DTI and fMRI. The superb seizure outcomes they report speak to the value of multimodal functional imaging in preventing neurological deficit while maximizing lesion resection. Similarly, Conti et al. describe their successful multimodal imaging approach to stereotactic CyberKnife radiosurgery, in which they combine not only fMRI and DTI but also nTMS to shape the treatment plan. Three retrospective series follow on the specific application of fMRI to preoperative sensorimotor and language mapping. Kundu et al. examine whether postoperative language outcomes after tumor surgery can be predicted by the proximity of tumors to preoperative language activations in the Broca and Wernicke areas. Voss Introduction

Presurgical navigated transcranial magnetic brain stimulation for recurrent gliomas in motor eloquent areas

ObjectiveNavigated transcranial magnetic stimulation (nTMS) has been repeatedly shown to be comparably accurate to direct cortical stimulation (DCS) for rolandic region mapping. However, there are no data on its use for recurrent gliomas in which scarring and radiotherapy can impair nTMS. We therefore evaluated the accuracy of nTMS versus DCS and functional MRI (fMRI) in recurrent gliomas compared to initially operated tumors. MethodsWe examined 8 patients with recurrent gliomas and 23 patients with initially operated lesions in or adjacent to the precentral gyrus by preoperative nTMS. ResultsPreoperative motor mapping correlated well with intraoperative DCS in recurrent gliomas (6.2±6.0mm), as well as in newly diagnosed tumor patients (5.7±4.6mm) with no significant difference. Compared to fMRI, the difference was larger for upper (recurrent: 8.5±7.2mm; new: 9.8±8.6mm) and lower (recurrent: 17.1±10.6mm; new: 13.8±13.0mm) extremities, with no significant differences. ConclusionsWhen comparing nTMS with DCS and fMRI, nTMS is as accurate in recurrent gliomas as it is prior to the first operation. It should be considered a helpful modality in recurrent glioma patients as well. SignificancenTMS is also applicable in recurrent tumors.