Mapping the Functional Boundaries of the Speech Articulation Network Using Positive and Negative Direct Electrical Stimulation With Resting-State Functional MRI

Neurosurgery 98:577–587, 2026

This clinical research integrates positive and negative direct electrical stimulation (DES) with presurgical resting-state fMRI to refine the speech articulation network (SAN) atlas in glioma patients. Analyzing 25 patients, the study maps DES-positive and DES-negative seed-based connectivity, compares anticorrelated networks, and evaluates sensitivity and specificity across group-frequency thresholds.

Key findings show DES-positive sites robustly identify bilateral SAN regions (rolandic operculum, inferior frontal and superior temporal gyri), while DES-negative points delineate functional borders and improve atlas specificity; a 41% SAN-positive threshold yields approximately 80% sensitivity and specificity for clinical use.

Resting-state fMRI and DES: Resting-state functional MRI (rs-fMRI) is a noninvasive tool for mapping brain networks, while direct electrical stimulation (DES) during awake surgery (AwS) is the gold standard for causally identifying functional brain regions, especially for speech articulation mapping in glioma patients.

Inclusion of DES-negative points: Incorporating both DES-positive (eliciting function) and DES-negative (no function elicited) points enables more precise mapping of the speech articulation network (SAN) and its functional borders, improving specificity and sensitivity compared to using only positive points.

Comprehensive SAN atlas: A new SAN atlas was created from 25 glioma patients using 32 DES-positive and 42 DES-negative points, with presurgical rs-fMRI seed-based connectivity analysis, providing a more accurate and clinically relevant definition of the SAN.

Distinct connectivity patterns: DES-positive points consistently mapped the SAN to bilateral rolandic operculum, inferior frontal gyrus, and superior temporal gyrus, while DES-negative points revealed distinct, only partially overlapping connectivity patterns, helping delineate the SAN’s functional borders.

Threshold for clinical use: A 41% frequency threshold for the SAN-positive network achieves approximately 80% sensitivity and specificity, offering a practical balance for clinical application in presurgical planning.

Functional borders and overlap: Minimal overlap between SAN-positive and SAN-negative networks identifies functional borders, especially in the precentral sulcus and inferior frontal gyrus, aiding neurosurgeons in distinguishing critical from non-critical areas during mapping.

Clinical implications: Defining precise SAN borders improves intraoperative decision-making, reduces irrelevant stimulation, shortens mapping time, and enhances safety in both awake and asleep brain surgeries.

Limitations and future directions: The study’s limitations include sample size, heterogeneity, and MRI field strength; future research should use larger, more homogeneous cohorts and higher-resolution imaging to further refine SAN mapping.

Awake surgery with mapping-based resection to treat focal epilepsy in eloquent brain areas

Acta Neurochirurgica (2024) 166:430

Resective surgery is a potential therapeutic option for select patients with intractable focal epilepsy. However, the presence of ictal onset zones within or surrounding highly functional brain areas presents a surgical challenge, leading to poor seizure and functional outcomes. This report describes our experiences with awake mapping-tailored resection of epileptogenic areas involving eloquent cortices and evaluates their feasibility, tolerance, limitations, and significance.

Methods The study included patients who underwent surgery for drug-resistant focal epilepsy at our center under awake conditions. The surgical approach aimed to achieve maximum resection of preoperatively defined epileptogenic zones, considering the boundaries defined by surrounding functional areas. We collected data on preoperative evaluations, intraoperative tests and seizures, postoperative status epilepticus, and neurological functional outcomes.

Results We included 22 patients, 10 of whom had non-lesional epilepsy. Language, motor function, and sensory function were at risk in 19, 9, and 4 patients, respectively. Resection was performed as planned in 14 (63.6%) patients, while modifications were necessary in 8 (36.4%) patients due to functional constraints. The mean follow-up duration was 29.8 months. Sixteen (72.7%) patients achieved Engel class Ia outcomes, indicating seizure freedom, while none of the patients experienced clinically significant permanent postoperative neurological deficits.

Significance Resective surgery with intraoperative brain mapping under awake conditions was a valid treatment option for achieving a cure in cases of drug-resistant focal epilepsy, even in situations in which the condition is considered inoperable due to the risk of significant postoperative neurological deficits.

Improvement of diffusion tensor imaging–based tractography by free-water correction in nonedematous gliomas: assessment with brain mapping

J Neurosurg 141:684–694, 2024

The free-water correction algorithm (Freewater Estimator Using Interpolated Initialization [FERNET]) can be applied to standard diffusion tensor imaging (DTI) tractography to improve visualization of subcortical bundles in the peritumoral area of highly edematous brain tumors. Interest in its use for presurgical planning in purely infiltrative gliomas without peritumoral edema has never been evaluated. Using subcortical maps obtained with direct electrostimulation (DES) in awake surgery as a reference standard, the authors sought to 1) assess the accuracy of preoperative DTIbased tractography with FERNET in a series of nonedematous glioma patients, and 2) determine its potential usefulness in presurgical planning.

METHODS Based on DES-induced functional disturbances and tumor topography, the authors retrospectively reconstructed the putatively stimulated bundles and the peritumoral tracts of interest (various associative and projection pathways) of 12 patients. The tractography data obtained with and without FERNET were compared.

RESULTS The authors identified 21 putative tracts from 24 stimulation sites and reconstituted 49 tracts of interest. The number of streamlines of the putative tracts crossing the DES area was 26.8% higher (96.04 vs 75.75, p = 0.016) and their volume 20.4% higher (13.99 cm 3 vs 11.62 cm 3 , p < 0.0001) with FERNET than with standard DTI. Additionally, the volume of the tracts of interest was 22.1% higher (9.69 cm 3 vs 7.93 cm 3 , p < 0.0001).

CONCLUSIONS Free-water correction significantly increased the anatomical plausibility of the stimulated fascicles and the volume of tracts of interest in the peritumoral area of purely infiltrative nonedematous gliomas. Because of the functional importance of the peritumoral zone, applying FERNET to DTI could have potential implications on surgical planning and the safety of glioma resection.

Functional Reorganization of the Mesial Frontal Premotor Cortex in Patients With Supplementary Motor Area Seizures

Neurosurgery 92:186–194, 2023

Direct cortical stimulation of the mesial frontal premotor cortex, including the supplementary motor area (SMA), is challenging in humans. Limited access to these brain regions impedes understanding of human premotor cortex functional organization and somatotopy.

OBJECTIVE: To test whether seizure onset within the SMA was associated with functional remapping of mesial frontal premotor areas in a cohort of patients with epilepsy who underwent awake brain mapping after implantation of interhemispheric subdural electrodes.

METHODS: Stimulation trials from 646 interhemispheric subdural electrodes were analyzed and compared between patients who had seizure onset in the SMA (n = 13) vs patients who had seizure onset outside of the SMA (n = 12). 1:1 matching with replacement between SMA and non-SMA data sets was used to ensure similar spatial distribution of electrodes. Centroids and 95% confidence regions were computed for clustered head, trunk, upper extremity, lower extremity, and vision responses. A generalized linear mixedeffects model was used to test for significant differences in the resulting functional maps. Clinical, radiographic, and histopathologic data were reviewed.

RESULTS: After analyzing direct cortical stimulation trials from interhemispheric electrodes, we found significant displacement of the head and trunk responses in SMA compared with non-SMA patients (P < .01 for both). These differences remained significant after accounting for structural lesions, preexisting motor deficits, and seizure outcome.

CONCLUSION: The somatotopy of the mesial frontal premotor regions is significantly altered in patients who have SMA-onset seizures compared with patients who have seizure onset outside of the SMA, suggesting that functional remapping can occur in these brain regions.

Personalized surgery of brain tumors in language areas: the role of preoperative brain mapping in patients not eligible for awake surgery

Neurosurg Focus 53 (6):E3, 2022

Awake surgery represents the gold standard for resection of brain tumors close to the language network. However, in some cases patients may be considered not eligible for awake craniotomy. In these cases, a personalized brain mapping of the language network may be achieved by navigated transcranial magnetic stimulation (nTMS), which can guide resection in patients under general anesthesia. Here the authors describe their tailored nTMS-based strategy and analyze its impact on the extent of tumor resection (EOR) and language outcome in a series of patients not eligible for awake surgery.

METHODS The authors reviewed data from all patients harboring a brain tumor in or close to the language network who were considered not eligible for awake surgery and were operated on during asleep surgery between January 2017 and July 2022, under the intraoperative guidance of nTMS data. The authors analyzed the effectiveness of nTMS-based mapping data in relation to 1) the ability of the nTMS-based mapping to stratify patients according to surgical risks, 2) the occurrence of postoperative language deficits, and 3) the EOR.

RESULTS A total of 176 patients underwent preoperative nTMS cortical language mapping and nTMS-based tractography of language fascicles. According to the nTMS-based mapping, tumors in 115 patients (65.3%) were identified as true-eloquent tumors because of a close spatial relationship with the language network. Conversely, tumors in 61 patients (34.7%) for which the nTMS mapping disclosed a location at a safer distance from the network were identified as false-eloquent tumors. At 3 months postsurgery, a permanent language deficit was present in 13 patients (7.3%).

In particular, a permanent deficit was observed in 12 of 115 patients (10.4%) with true-eloquent tumors and in 1 of 61 patients (1.6%) with false-eloquent lesions. With nTMS-based mapping, neurosurgeons were able to distinguish trueeloquent from false-eloquent tumors in a significant number of cases based on the occurrence of deficits at discharge (p < 0.0008) and after 3 months from surgery (OR 6.99, p = 0.03). Gross-total resection was achieved in 80.1% of patients overall and in 69.5% of patients with true-eloquent lesions and 100% of patients with false-eloquent tumors.

CONCLUSIONS nTMS-based mapping allows for reliable preoperative mapping of the language network that may be used to stratify patients according to surgical risks. nTMS-guided asleep surgery should be considered a good alternative for personalized preoperative brain mapping of the language network that may increase the possibility of safe and effective resection of brain tumors in the dominant hemisphere whenever awake mapping is not feasible.

Recurrent Low-Grade Gliomas: Does Reoperation Affect Neurocognitive Functioning?

Neurosurgery 90:221–232, 2022

Reoperations in patients with recurrent low-grade gliomas (RLGG) were proposed to control tumor residual and delay the risk of malignant transformation over time.

OBJECTIVE: To investigate neurocognitive outcomes in patients with RLGG who underwent a second surgery with awake monitoring.

METHODS: In this retrospective study, patients who underwent a second awake surgery for RLGG were included. Patients had presurgical and 3-mo postsurgical neuropsychological assessments. Data were converted into Z-scores and combined by the cognitive domain. Number of patients with cognitive deficits (Z-score <À1.65), variations of Z-scores, and extent of resection (EOR) were analyzed.

RESULTS: Sixty-two patients were included (mean age: 41.2 ± 10.0 yr). None had permanent neurological deficits postoperatively. Eight patients (12.9%) had a cognitive deficit preoperatively. Four additional patients (6.5%) had a cognitive deficit 3 mo after reoperation. Among other patients, 13 (21.0%) had a mild decline without cognitive deficits while 29 (46.8%) had no change of their performances and 8 (12.9%) improved. Overall, 94.2% of the patients returned to work. There were no correlations between EOR and Z-scores. Total/ subtotal resections were achieved in 91.9% of the patients (mean residual: 3.1 cm3 ). Fiftyeight patients (93.5%) were still alive after an overall follow-up of 8.3 yr.

CONCLUSION: Reoperation with awake monitoring in patients with RLGG was compatible with an early recovery of neuropsychological abilities. Four patients (6.5%) presented a new cognitive deficit at 3 mo postoperatively. Total/subtotal resections were achieved in most patients. Based on these favorable outcomes, reoperation should be considered in a more systematic way.

Incidental Low-Grade Gliomas: Single-Institution Management Based on Clinical, Surgical, and Molecular Data

Neurosurgery 2019 DOI:10.1093/neuros/nyz114

Incidentally discovered diffuse low-grade gliomas (iLGG) are poorly documented in the literature. They are diagnosed by chance during radiological examinations.

OBJECTIVE: To review a cohort of patients with iLGG surgically treated in our institution, analyzing clinical, molecular, and surgical aspects.

METHODS: Clinical, radiological, and treatment data of iLGGwere retrieved and compared with those of symptomatic diffuse LGGs (sLGG). Histological and molecular review was carried out as well. The extent of resection was evaluated on preoperative and postoperative T2-weighted magnetic resonance imaging.

RESULTS: Thirty-four iLGG cases were identified within a monoinstitutional cohort of 332 patients operated for low-grade gliomas from 2000 to 2017. Clinically, patients with iLGG had higher preoperative karnofsky performance scale (KPS) (P = .003), smaller tumor volume (P=.0001), lower frequency of eloquent areas involvement (P=.0001), and higher rate of complete resection (P = .0001) compared to those with sLGG. No differences in the molecular profile and O6-methylguanine-DNA-methyltransferase promoter methylation were detected between iLGG and sLGG. Importantly, patients with iLGG had longer overall survival than those with sLGG (P = .0001), even when a complete surgical resection was achieved (P = .001).

CONCLUSION: Although the therapeutic strategy of iLGG is still a matter of debate, our data support the safety and the effectiveness of early surgical resection. The favorable prognosis of iLGG may be due to the higher practicability of extensive resection, noneloquent tumor location, and smaller tumor volume.

Neurophysiological examination combined with functional intraoperative navigation using TMS in patients with brain tumor near the central region

Acta Neurochirurgica (2019) 161:1853–1864

Feasibility and value of non-invasive transcranial magnetic brain stimulation (TMS MAGVENTURE® MagPro R30 Denmark) for preoperative diagnosis and surgical planning of brain tumor operations in everyday clinical practice.

Methods A prospective monocentric study was conducted, which included preoperative neurological and electrophysiological examination, TMS, and display of functional data in the navigation system (LOCALITE® TMS Navigator Germany). During surgery, the TMS data were correlated with the intraoperative monitoring (IOM). Twenty-four hours to 96 h and after at least 3 months, follow-ups with neurological, electrophysiological examinations and TMS stimulation were performed.

Results Twenty-five patients with tumors in or near by the primary motor cortex region were included in the study. Twenty-one patients completed preoperative and first postoperative TMS and the neurological examination. Eight of 21 patients showed slight worsening of primary motor cortex function, 8 patients had an unchanged state, and 4 patients showed an improvement early after surgery. The changes of the electrophysiological examination like significant delay of the latency and/or reduced amplitudes matched well with the postoperative neurological outcome: if patients showed a worsening of the SEP’s and MEP’s, the postoperative results revealed deterioration.

Conclusion A preoperatively performed TMS using the MAGVENTURE® MagPro R30 and the LOCALITE® TMS Navigator could be established in our clinical daily practice and allowed a safe and reliable mapping of the primary motor cortex in order to minimize the risk of postoperative neurological deficits and improve the neurological outcome of the patients.

Inhibition of Manual Movements at Speech Arrest Sites in the Posterior Inferior Frontal Lobe

Neurosurgery 85:E496–E501, 2019

Intraoperative stimulation of the posterior inferior frontal lobe (IFL) induces speech arrest, which is often interpreted as demonstration of essential language function. However, prior reports have described “negative motor areas” in the IFL, sites where stimulation halts ongoing limb motor activity.

OBJECTIVE: To investigate the spatial and functional relationship between IFL speech arrest areas and negative motor areas (NMAs).

METHODS: In this retrospective cohort study, intraoperative stimulation mapping was performed to localize speech and motor function, as well as arrest of hand movement, hand posture, and guitar playing in a set of patients undergoing awake craniotomy for dominant hemisphere pathologies. The incidence and localization of speech arrest and motor inhibition was analyzed.

RESULTS: Eleven patients underwent intraoperative localization of speech arrest sites and inhibitory motor areas. A total of 17 speech arrest sites were identified in the dominant frontal lobe, and, of these, 5 sites (29.4%) were also identified as NMAs. Speech arrest and arrest of guitar playing was also evoked by a single IFL site in 1 subject.

CONCLUSION: Inferior frontal gyrus speech arrest sites do not function solely in speech production. These findings provide further evidence for the complexity of language organization, and suggest the need for refined mapping strategies that discern between language-specific sites and inhibitory motor areas.

 

 

Robot-assisted stereoelectroencephalography in children

J Neurosurg Pediatr 23:288–296, 2019

The goal in the study was to describe the clinical outcomes associated with robot-assisted stereoelectroencephalography (SEEG) in children.

METHODS The authors performed a retrospective, single-center study in consecutive children with medically refractory epilepsy who were undergoing robot-assisted SEEG. Kaplan-Meier survival analysis was used to calculate the probability of seizure freedom. Both univariate and multivariate methods were used to analyze the preoperative and operative factors associated with seizure freedom.

RESULTS Fifty-seven children underwent a total of 64 robot-assisted procedures. The patients’ mean age was 12 years, an average of 6.4 antiepileptic drugs (AEDs) per patient had failed prior to implantation, and in 56% of the patients the disease was considered nonlesional. On average, children had 12.4 electrodes placed per implantation, with an implantation time of 9.6 minutes per electrode and a 10-day postoperative stay. SEEG analysis yielded a definable epileptogenic zone in 51 (89%) patients; 42 (74%) patients underwent surgery, half of whom were seizure free at last follow-up, 19.6 months from resection. In a multivariate generalized linear model, resective surgery, older age, and shorter SEEGrelated hospital length of stay were associated with seizure freedom. In a Cox proportional hazards model including only the children who underwent resective surgery, older age was the only significant factor associated with seizure freedom. Complications related to bleeding were the major contributors to morbidity. One patient (1.5%) had a symptomatic hemorrhage resulting in a permanent neurological deficit.

CONCLUSIONS The authors report one of the largest pediatric-specific SEEG series demonstrating that the modern surgical management of medically refractory epilepsy in children can lead to seizure freedom in many patients, while also highlighting the challenges posed by this difficult patient population.

 

Insular glioma surgery: an evolution of thought and practice


J Neurosurg 130:9–16, 2019

The goal of this article is to review the history of surgery for low- and high-grade gliomas located within the insula with particular focus on microsurgical technique, anatomical considerations, survival, and postoperative morbidity.

METHODS The authors reviewed the literature for published reports focused on insular region anatomy, neurophysiol- ogy, surgical approaches, and outcomes for adults with World Health Organization grade II–IV gliomas.

RESULTS While originally considered to pose too great a risk, insular glioma surgery can be performed safely due to the collective efforts of many individuals. Similar to resection of gliomas located within other cortical regions, maximal resection of gliomas within the insula offers patients greater survival time and superior seizure control for both newly diagnosed and recurrent tumors in this region. The identification and the preservation of M2 perforating and lateral len- ticulostriate arteries are critical steps to preventing internal capsule stroke and hemiparesis. The transcortical approach and intraoperative mapping are useful tools to maximize safety.

CONCLUSIONS The insula’s proximity to middle cerebral and lenticulostriate arteries, primary motor areas, and perisyl- vian language areas makes accessing and resecting gliomas in this region challenging. Maximal safe resection of insular gliomas not only is possible but also is associated with excellent outcomes and should be considered for all patients with low- and high-grade gliomas in this area.

Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound

J Neurosurg 128:875–884, 2018

Ultrasound can be precisely focused through the intact human skull to target deep regions of the brain for stereotactic ablations. Acoustic energy at much lower intensities is capable of both exciting and inhibiting neural tissues without causing tissue heating or damage. The objective of this study was to demonstrate the effects of low-intensity focused ultrasound (LIFU) for neuromodulation and selective mapping in the thalamus of a large-brain animal.

METHODS Ten Yorkshire swine (Sus scrofa domesticus) were used in this study. In the first neuromodulation experiment, the lemniscal sensory thalamus was stereotactically targeted with LIFU, and somatosensory evoked potentials (SSEPs) were monitored. In a second mapping experiment, the ventromedial and ventroposterolateral sensory thalamic nuclei were alternately targeted with LIFU, while both trigeminal and tibial evoked SSEPs were recorded. Temperature at the acoustic focus was assessed using MR thermography. At the end of the experiments, all tissues were assessed histologically for damage.

RESULTS LIFU targeted to the ventroposterolateral thalamic nucleus suppressed SSEP amplitude to 71.6% ± 11.4% (mean ± SD) compared with baseline recordings. Second, we found a similar degree of inhibition with a high spatial resolution (~ 2 mm) since adjacent thalamic nuclei could be selectively inhibited. The ventromedial thalamic nucleus could be inhibited without affecting the ventrolateral nucleus. During MR thermography imaging, there was no observed tissue heating during LIFU sonications and no histological evidence of tissue damage.

CONCLUSIONS These results suggest that LIFU can be safely used to modulate neuronal circuits in the central nervous system and that noninvasive brain mapping with focused ultrasound may be feasible in humans.

Variability of intraoperative electrostimulation parameters in conscious individuals: language cortex

J Neurosurg 126:1641–1652, 2017

Electrostimulation in awake brain mapping is widely used to guide tumor removal, but methodologies can differ substantially across institutions. The authors studied electrostimulation brain mapping data to characterize the variability of the current intensity threshold across patients and the effect of its variations on the number, type, and surface area of the essential language areas detected.

METHODS Over 7 years, the authors prospectively studied 100 adult patients who were undergoing intraoperative brain mapping during resection of left hemisphere tumors. In all 100 cases, the same protocol of electrostimulation brain mapping (a controlled naming task—bipolar stimulation with biphasic square wave pulses of 1-msec duration and 60-Hz trains, maximum train duration 6 sec) and electrocorticography was used to detect essential language areas.

RESULTS The minimum positive thresholds of stimulation varied from patient to patient; the mean minimum intensity required to detect interference was 4.46 mA (range 1.5–9 mA), and in a substantial proportion of sites (13.5%) interference was detected only at intensities above 6 mA. The threshold varied within a given patient for different naming areas in 22% of cases. Stimulation of the same naming area with greater intensities led to slight changes in the type of response in 19% of cases and different types of responses in 4.5%. Naming sites detected were located in subcentimeter cortical areas (50% were less than 20 mm2), but their extent varied with the intensity of stimulation. During a brain mapping session, the same intensity of stimulation reproduced the same type of interference in 94% of the cases. There was no statistically significant difference between the mean stimulation intensities required to produce interfereince in the left inferior frontal lobe (Broca’s area), the supramarginal gyri, and the posterior temporal region.

CONCLUSIONS Intrasubject and intersubject variations of the minimum thresholds of positive naming areas and changes in the type of response and in the size of these areas according to the intensity used may limit the interpretation of data from electrostimulation in awake brain mapping. To optimize the identification of language areas during electrostimulation brain mapping, it is important to use different intensities of stimulation at the maximum possible currents, avoiding afterdischarges. This could refine the clinical results and scientific data derived from these mapping sessions.

Surgical treatment of brain metastases in the central region

J Neurosurg 126:698–707, 2017

Brain metastases are the most frequent intracranial malignant tumor in adults. Surgical intervention for metastases in eloquent areas remains controversial and challenging. Even when metastases are not in ltrating intra- parenchymal tumors, eloquent areas can be affected. Therefore, this study aimed to describe the role of a functional guided approach for the resection of brain metastases in the central region.

METHODS Thirty-three patients (19 men and 14 women) with perirolandic metastases who were treated at the authors’ institution were reviewed. All participants underwent resection using a functional guided approach, which consisted of using intraoperative brain mapping and/or neurophysiological monitoring to aid in the resection, depending on the functionality of the brain parenchyma surrounding each metastasis. Motor and sensory functions were monitored in all patients, and supplementary motor and language area functions were assessed in 5 and 4 patients, respectively. Clinical data were analyzed at presentation, discharge, and the 6-month follow-up.

RESULTS The most frequent presenting symptom was seizure, followed by paresis. Gross-total removal of the metastasis was achieved in 31 patients (93.9%). There were 6 deaths during the follow-up period. After the removal of the metastasis, 6 patients (18.2%) presented with transient neurological worsening, of whom 4 had worsening of motor function impairment and 2 had acquired new sensory disturbances. Total recovery was achieved before the 3rd month of follow-up in all cases. Excluding those patients who died due to the progression of systemic illness, 88.9% of patients had a Karnofsky Performance Scale score greater than 80% at the 6-month follow-up. The mean survival time was 24.4 months after surgery.

CONCLUSIONS The implementation of intraoperative electrical brain stimulation techniques in the resection of central region metastases may improve surgical planning and resection and may spare eloquent areas. This approach also facilitates maximal resection in these and other critical functional areas, thereby helping to avoid new postoperative neurological deficits. Avoiding permanent neurological de cits is critical for a good quality of life, especially in patients with a life expectancy of over a year.

Maximizing safe resection of low- and high-grade glioma

dti-gliomas

J Neurooncol (2016) 130:269–282

Surgical resection plays a central role in the management of gliomas. In this study, we review the evidence in support of extent of resection to improve survival, symptom management, and time to malignant transformation in low- and high-grade gliomas, and summarize the findings from our literature search regarding the role of extent of resection and intraoperative practices to maximize safety.

There is a growing body of evidence supporting improved overall survival, improved progression-free survival, and superior quality of life with greater extent of resection.

Additionally, a better understanding of central nervous system plasticity allows for a staged approach to the surgical management of low- and intermediate-grade gliomas.

A number of intraoperative techniques have been utilized to offer safer glioma surgery with greater extent of resection. Approaches such as awake brain tumor surgery can be safely performed with low failure rates and excellent long-term functional outcomes.

Identification of language area and the pars triangularis

language-area-and-pt

Journal of Neurosurgery Vol. 125 / No. 4 : 803-811

Identification of language areas using functional brain mapping is sometimes impossible using current methods but essential to preserve language function in patients with gliomas located within or near the frontal language area (FLA). However, the factors that influence the failure to detect language areas have not been elucidated. The present study evaluated the difficulty in identifying the FLA in dominant-side frontal gliomas that involve the pars triangularis (PT) to determine the factors that influenced failed positive language mapping.

Methods: Awake craniotomy was performed on 301 patients from April 2000 to October 2013 at Tokyo Women’s Medical University. Recurrent cases were excluded, and patients were also excluded if motor mapping indicated their glioma was in or around the motor area on the dominant or nondominant side. Eighty-two consecutive cases of primary frontal glioma on the dominant side were analyzed for the present study. MRI was used for all patients to evaluate whether tumors involved the PT and to perform language functional mapping with a bipolar electrical stimulator. Eighteen of 82 patients (mean age 39 ± 13 years) had tumors that showed involvement of the PT, and the detailed characteristics of these 18 patients were examined.

Results: The FLA could not be identified with intraoperative brain mapping in 14 (17%) of 82 patients; 11 (79%) of these 14 patients had a tumor involving the PT. The negative response rate in language mapping was only 5% in patients without involvement of the PT, whereas this rate was 61% in patients with involvement of the PT. Univariate analyses showed no significant correlation between identification of the FLA and sex, age, histology, or WHO grade. However, failure to identify the FLA was significantly correlated with involvement of the PT (p < 0.0001). Similarly, multivariate analyses with the logistic regression model showed that only involvement of the PT was significantly correlated with failure to identify the FLA (p < 0.0001). In 18 patients whose tumors involved the PT, only 1 patient had mild preoperative dysphasia. One week after surgery, language function worsened in 4 (22%) of 18 patients. Six months after surgery, 1 (5.6%) of 18 patients had a persistent mild speech deficit. The mean extent of resection was 90% ± 7.1%.

Conclusions: Identification of the FLA can be difficult in patients with frontal gliomas on the dominant side that involve the PT, but the positive mapping rate of the FLA was 95% in patients without involvement of the PT. These findings are useful for establishing a positive mapping strategy for patients undergoing awake craniotomy for the treatment of frontal gliomas on the dominant side. Thoroughly positive language mapping with subcortical electrical stimulation should be performed in patients without involvement of the PT. More careful continuous neurological monitoring combined with subcortical electrical stimulation is needed when removing dominant-side frontal gliomas that involve the PT.

Identification of language area and the pars triangularis

language-area-and-pt

J Neurosurg 125:803–811, 2016

Identification of language areas using functional brain mapping is sometimes impossible using current methods but essential to preserve language function in patients with gliomas located within or near the frontal language area (FLA). However, the factors that influence the failure to detect language areas have not been elucidated. The present study evaluated the difficulty in identifying the FLA in dominant-side frontal gliomas that involve the pars triangularis (PT) to determine the factors that influenced failed positive language mapping.

Methods: Awake craniotomy was performed on 301 patients from April 2000 to October 2013 at Tokyo Women’s Medical University. Recurrent cases were excluded, and patients were also excluded if motor mapping indicated their glioma was in or around the motor area on the dominant or nondominant side. Eighty-two consecutive cases of primary frontal glioma on the dominant side were analyzed for the present study. MRI was used for all patients to evaluate whether tumors involved the PT and to perform language functional mapping with a bipolar electrical stimulator. Eighteen of 82 patients (mean age 39 ± 13 years) had tumors that showed involvement of the PT, and the detailed characteristics of these 18 patients were examined.

Results: The FLA could not be identified with intraoperative brain mapping in 14 (17%) of 82 patients; 11 (79%) of these 14 patients had a tumor involving the PT. The negative response rate in language mapping was only 5% in patients without involvement of the PT, whereas this rate was 61% in patients with involvement of the PT. Univariate analyses showed no significant correlation between identification of the FLA and sex, age, histology, or WHO grade. However, failure to identify the FLA was significantly correlated with involvement of the PT (p < 0.0001). Similarly, multivariate analyses with the logistic regression model showed that only involvement of the PT was significantly correlated with failure to identify the FLA (p < 0.0001). In 18 patients whose tumors involved the PT, only 1 patient had mild preoperative dysphasia. One week after surgery, language function worsened in 4 (22%) of 18 patients. Six months after surgery, 1 (5.6%) of 18 patients had a persistent mild speech deficit. The mean extent of resection was 90% ± 7.1%.

Conclusions: Identification of the FLA can be difficult in patients with frontal gliomas on the dominant side that involve the PT, but the positive mapping rate of the FLA was 95% in patients without involvement of the PT. These findings are useful for establishing a positive mapping strategy for patients undergoing awake craniotomy for the treatment of frontal gliomas on the dominant side. Thoroughly positive language mapping with subcortical electrical stimulation should be performed in patients without involvement of the PT. More careful continuous neurological monitoring combined with subcortical electrical stimulation is needed when removing dominant-side frontal gliomas that involve the PT.

Mapping of cortical language function by functional magnetic resonance imaging and repetitive navigated transcranialmagnetic stimulation in 40 healthy subjects

Mapping of cortical language function by functional magnetic resonance imaging and repetitive navigated transcranial magnetic stimulation in 40 healthy subjects

Acta Neurochir (2016) 158:1303–1316

Functional magnetic resonance imaging (fMRI) is considered to be the standard method regarding noninvasive language mapping. However, repetitive navigated transcranial magnetic stimulation (rTMS) gains increasing importance with respect to that purpose. However, comparisons between both methods are sparse.

Methods We performed fMRI and rTMS language mapping of the left hemisphere in 40 healthy, right-handed subjects in combination with the tasks that are most commonly used in the neurosurgical context (fMRI: word-generation=WGEN task; rTMS: object-naming=ON task). Different rTMS error rate thresholds (ERTs) were calculated, and Cohen’s kappa coefficient and the cortical parcellation system (CPS) were used for systematic comparison of the two techniques.

Results Overall, mean kappa coefficients were low, revealing no distinct agreement. We found the highest agreement for both techniques when using the 2-out-of-3 rule (CPS region defined as language positive in terms of rTMS if at least 2 out of 3 stimulations led to a naming error). However, kappa for this threshold was only 0.24 (kappa of <0, 0.01–0.20, 0.21– 0.40, 0.41–0.60, 0.61–0.80 and 0.81–0.99 indicate less than chance, slight, fair, moderate, substantial and almost perfect agreement, respectively).

Conclusions Because of the inherent differences in the underlying physiology of fMRI and rTMS, the different tasks used and the impossibility of verifying the results via direct cortical stimulation (DCS) in the population of healthy volunteers, one must exercise caution in drawing conclusions about the relative usefulness of each technique for language mapping. Nevertheless, this study yields valuable insights into these two mapping techniques for the most common language tasks currently used in neurosurgical practice.

fMRI activation in the middle frontal gyrus as an indicator of hemispheric dominance for language in brain tumor patients: a comparison with Broca’s area

Functional imaging

Neuroradiology (2016) 58:513–520

Functional MRI (fMRI) can assess language lateralization in brain tumor patients; however, this can be limited if the primary language area—Broca’s area (BA)—is affected by the tumor. We hypothesized that the middle frontal gyrus (MFG) can be used as a clinical indicator of hemispheric dominance for language during presurgical workup.

Methods: Fifty-two right-handed subjects with solitary left hemispheric primary brain tumors were retrospectively studied. Subjects performed a verbal fluency task during fMRI. The MFG was compared to BA for fMRI voxel activation, language laterality index (LI), and the effect of tumor grade on the LI.

Results: Language fMRI (verbal fluency) activated more voxels in MFG than in BA (MFG=315, BA=216, p<0.001). Voxel activations in the left-hemispheric MFG and BA were positively correlated (r = 0.69, p < 0.001). Mean LI in the MFG was comparable to that in BA (MFG = 0.48, BA = 0.39, p = 0.06). LIs in MFG and BA were positively correlated (r = 0.62, p < 0.001). Subjects with high- grade tumors demonstrate lower language lateralization than those with low-grade tumors in both BA and MFG (p = 0.02, p = 0.02, respectively).

Conclusion: MFG is comparable to BA in its ability to indicate hemispheric dominance for language using a measure of verbal fluency and may be an adjunct measure in the clinical determination of language laterality for presurgical planning.

The Impact of Sedation on Brain Mapping

Brain Mapping

Neurosurgery 75:117–123, 2014

During awake craniotomies, patients may either be awake for the entire duration of the surgical intervention (awake-awake-awake craniotomy, AAA) or initially sedated (asleep-awake-asleep craniotomy, SAS).

OBJECTIVE: To examine whether prior sedation in SAS may restrict brain mapping, we conducted neuropsychological tests in patients by means of a standardized anesthetic regimen comparable to an SAS.

METHODS: We prospectively examined patients undergoing surgery either under total intravenous anesthesia (TIVA) or under regional anesthesia with slight sedation (RAS). The tests included the DO40 picture-naming test, the digit span, the Regensburg Word Fluency Test, and the finger-tapping test. Each test was conducted 3 times for every patient in the TIVA and RAS groups, once before surgery and twice within about 35 minutes after the end of sedation. Patients undergoing AAA were examined preoperatively and intraoperatively.

RESULTS: In the AAA group, no significant difference was found between preoperative and intraoperative test results. In the TIVA and RAS groups, postoperative tests showed worse results than preoperative tests. In most tests, patients improved from the first to the second postoperative test.

CONCLUSION: Cognitive and motor performance were significantly influenced by prior sedation in the TIVA and RAS groups, but not in the AAA group. Therefore, prior sedation may be assumed to cause a change in the baselines, which may compromise brain mapping and thus endanger a patient’s neurological outcome in the case of an SAS.