Functional maps of direct electrical stimulation-induced speech arrest and anomia: a multicentre retrospective study.

Direct electrical stimulation, the transient 'lesional' method probing brain function, has been utilized in identifying the language cortex and preserving language function during epilepsy and neuro-oncological surgeries for about a century. However, comparison of functional maps of the language cortex across languages/continents based on cortical stimulation remains unclear. We conducted a retrospective multicentre study including four cohorts of direct electrical stimulation mapping from four centres across three continents, where three indigenous languages (English, French and Mandarin) are spoken. All subjects performed the two most common language tasks: number counting and picture naming during stimulation. All language sites were recorded and normalized to the same brain template. Next, Spearman's correlation analysis was performed to explore the consistency of the distributions of the language cortex across centres, a kernel density estimation to localize the peak coordinates, and a hierarchical cluster analysis was performed to detect the crucial epicenters. A total of 598 subjects with 917 speech arrest sites (complete interruption of ongoing counting) and 423 anomia sites (inability to name or misnaming) were included. Different centres presented highly consistent distribution patterns for speech arrest (Spearman's coefficient r ranged from 0.60 to 0.85, all pair-wise correlations P < 0.05), and similar patterns for anomia (Spearman's coefficient r ranged from 0.37 to 0.80). The combinational speech arrest map was divided into four clusters: cluster 1 mainly located in the ventral precentral gyrus and pars opercularis, which contained the peak of speech arrest in the ventral precentral gyrus; cluster 2 in the ventral and dorsal precentral gyrus; cluster 3 in the supplementary motor area; cluster 4 in the posterior superior temporal gyrus and supramarginal gyrus. The anomia map revealed two clusters: one was in the posterior part of the superior and middle temporal gyri, which peaked at the posterior superior temporal gyrus; and the other within the inferior frontal gyrus, peaked at the pars triangularis. This study constitutes the largest series to date of language maps generated from direct electrical stimulation mapping. The consistency of data provides evidence for common language networks across languages, in the context of both speech and naming circuit. Our results not only clinically offer an atlas for language mapping and protection, but also scientifically provide better insight into the functional organization of language networks.

Probabilistic mapping of language networks from high frequency activity induced by direct electrical stimulation.

Direct electrical stimulation (DES) at 50 Hz is used as a gold standard to map cognitive functions but little is known about its ability to map large-scale networks and specific subnetwork. In the present study, we aim to propose a new methodological approach to evaluate the specific hypothesis suggesting that language errors/dysfunction induced by DES are the result of large-scale network modification rather than of a single cortical region, which explains that similar language symptoms may be observed after stimulation of different cortical regions belonging to this network. We retrospectively examined 29 patients suffering from focal drug-resistant epilepsy who benefitted from stereo-electroencephalographic (SEEG) exploration and exhibited language symptoms during a naming task following 50 Hz DES. We assessed the large-scale language network correlated with behavioral DES-induced responses (naming errors) by quantifying DES-induced changes in high frequency activity (HFA, 70-150 Hz) outside the stimulated cortical region. We developed a probabilistic approach to report the spatial pattern of HFA modulations during DES-induced language errors. Similarly, we mapped the pattern of after-discharges (3-35 Hz) occurring after DES. HFA modulations concurrent to language symptoms revealed a brain network similar to our current knowledge of language gathered from standard brain mapping. In addition, specific subnetworks could be identified within the global language network, related to different language processes, generally described in relation to the classical language regions. Spatial patterns of after-discharges were similar to HFA induced during DES. Our results suggest that this new methodological DES-HFA mapping is a relevant approach to map functional networks during SEEG explorations, which would allow to shift from "local" to "network" perspectives.

Proposal of an optimized strategy for intraoperative testing of speech and language during awake mapping.

In this paper, we review the literature about the definitions of errors observed by direct electrical stimulation during language testing. As a practical application, we propose an optimized strategy for differentiating accurately motor arrest, speech arrest, and anomia in the context of intraoperative mapping. Finally, we also discuss the anatomical correlates of the networks sustaining these different errors, both cortically and axonally.

Speech and lexico-semantic errors during direct cortical stimulation mapping of the language-dominant hemisphere: effects of object and action naming.

OBJECTIVE: In this retrospective study, the authors aimed to establish the stereotactically defined probability distribution for speech (i.e., anarthria, speech arrest) and lexico-semantic errors (i.e., anomia) through direct cortical stimulation (DCS) by using two tasks: action naming and object naming. They also analyzed the patterns of interindividual variability in the localization of the language sites involved, and investigated whether any patient or lesion location factors were associated with greater variability. METHODS: Eighty-one Italian-speaking patients who underwent awake surgery between 2010 and 2021 for low- and high-grade gliomas in eloquent areas of the language-dominant hemisphere were entered in the analyses. The intraoperative DCS protocol included automatic speech tasks, object naming, and action naming. The position of the tags, as depicted on the intraoperative video or photograph, was transposed into Montreal Neurological Institute space. Subsequently, a 2D scatterplot and cluster analysis were performed. Associations between various clinical and radiological characteristics and the quantity of positive stimulated sites were determined by univariate analyses using binary logistic regression. Associated variables (p < 0.2) were included in stepwise multivariate logistic regression with backward elimination (p < 0.05). RESULTS: A total of 1380 cortical sites were stimulated, with a positive response in 511 cases (37%). Most anarthric errors were triggered when stimulating the left precentral gyrus, and most speech arrest errors were elicited when stimulating the left posterior inferior frontal gyrus. Anomias were found in the left inferior frontal gyrus and in the posterior part of the left temporal lobe for object naming. DCS to the left dorsal premotor cortex elicited anomic errors for action naming. Anomias were also elicited during DCS to the left posterior temporal lobe, with both object and action naming. CONCLUSIONS: The distribution of speech and lexico-semantic errors is in line with the current literature. The action-naming results are new and mostly involve the dorsal premotor cortex. These findings stress the importance of maximizing the use of different language tasks during surgery, because even when looking for the same type of errors, different tasks may be better suited to map specific brain regions. DCS with action and object naming identifies more positive sites than object naming alone.

Language mapping with navigated repetitive TMS: proof of technique and validation.

OBJECTIVE: Lesion-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. METHODS: Subjects 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. RESULTS: nTMS 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. CONCLUSION: Maps 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.

Speech arrest by repetitive Transcranial Magnetic Stimulation - does it still work? Old experiences with new improvements.

BACKGROUND: Traditional repetitive Transcranial Magnetic Stimulation (rTMS) remains applicable in speech studies on healthy participants. Although the procedure of inducing speech arrest by rTMS has been used for over 25 years, there are still significant discrepancies in its methodology. OBJECTIVE: The study aimed to simplify and improve the old methodology of triggering speech arrest by (rTMS). Our goal was to establish the best step-by-step algorithm and verify the procedure on a representative group of participants. METHODS: 47 healthy, right-handed volunteers (23 men and 24 women) at a median age of 23 (range 19-34) were included in the study. Handedness was determined using the Edinburgh Handedness Inventory Test. After setting the individual's motor threshold (MT) and heuristic choice of the place of stimulation, which targeted Inferior Frontal Gyrus (IFG), participants were asked to count downwards from 20 to 10. While counting, a series of 2-second pulses was generated at a frequency of 2 Hz at 120% or 150% of MT. The procedure was video-recorded and subsequently assessed by 3 independent reviewers and self-assessed by participants on visual analogue scales for the effect and comfort of stimulation. RESULTS: Speech arrest was induced in 45 people (95.7%). Language dominance was determined to be either left-sided (for 42.2%) or bilateral (55.3%). Total speech arrest was observed more often in participants for whom Broca's area was active exclusively in the left hemisphere. CONCLUSION: In our study, we present the step-by-step procedure for a simplified, as far as possible, methodology of inducing speech arrest using rTMS with its verification on a representative group of right-handed healthy individuals. Our results prove that the chosen stimulation parameters present a good efficacy ratio and seems to be justified. The traditional applications of rTMS in speech studies may be highly broadened if the methods used are further improved and simplified.

Middle Frontal Gyrus and Area 55b: Perioperative Mapping and Language Outcomes.

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

Prediction of Speech Onset by Micro-Electrocorticography of the Human Brain.

Recent technological advances show the feasibility of offline decoding speech from neuronal signals, paving the way to the development of chronically implanted speech brain computer interfaces (sBCI). Two key steps that still need to be addressed for the online deployment of sBCI are, on the one hand, the definition of relevant design parameters of the recording arrays, on the other hand, the identification of robust physiological markers of the patient's intention to speak, which can be used to online trigger the decoding process. To address these issues, we acutely recorded speech-related signals from the frontal cortex of two human patients undergoing awake neurosurgery for brain tumors using three different micro-electrocorticographic ([Formula: see text]ECoG) devices. First, we observed that, at the smallest investigated pitch (600[Formula: see text][Formula: see text]m), neighboring channels are highly correlated, suggesting that more closely spaced electrodes would provide some redundant information. Second, we trained a classifier to recognize speech-related motor preparation from high-gamma oscillations (70-150[Formula: see text]Hz), demonstrating that these neuronal signals can be used to reliably predict speech onset. Notably, our model generalized both across subjects and recording devices showing the robustness of its performance. These findings provide crucial information for the design of future online sBCI.

Electrical stimulation-induced speech-related negative motor responses in the lateral frontal cortex.

OBJECTIVE: Speech arrest is a common but crucial negative motor response (NMR) recorded during intraoperative brain mapping. However, recent studies have reported nonspeech-specific NMR sites in the ventral precentral gyrus (vPrCG), where stimulation halts both speech and ongoing hand movement. The aim of this study was to investigate the spatial relationship between speech-specific NMR sites and nonspeech-specific NMR sites in the lateral frontal cortex. METHODS: In this prospective cohort study, an intraoperative mapping strategy was designed to identify positive motor response (PMR) sites and NMR sites in 33 consecutive patients undergoing awake craniotomy for the treatment of left-sided gliomas. Patients were asked to count, flex their hands, and simultaneously perform these two tasks to map NMRs. Each site was plotted onto a standard atlas and further analyzed. The speech and hand motor arrest sites in the supplementary motor area of 2 patients were resected. The 1- and 3-month postoperative language and motor functions of all patients were assessed. RESULTS: A total of 91 PMR sites and 72 NMR sites were identified. NMR and PMR sites were anteroinferiorly and posterosuperiorly distributed in the precentral gyrus, respectively. Three distinct NMR sites were identified: 24 pure speech arrest (speech-specific NMR) sites (33.33%), 7 pure hand motor arrest sites (9.72%), and 41 speech and hand motor arrest (nonspeech-specific NMR) sites (56.94%). Nonspeech-specific NMR sites and speech-specific NMR sites were dorsoventrally distributed in the vPrCG. For language function, 1 of 2 patients in the NMA resection group had language dysfunction at the 1-month follow-up but had recovered by the 3-month follow-up. All patients in the NMA resection group had fine motor dysfunction at the 1- and 3-month follow-ups. CONCLUSIONS: The study results demonstrated a functional segmentation of speech-related NMRs in the lateral frontal cortex and that most of the stimulation-induced speech arrest sites are not specific to speech. A better understanding of the spatial distribution of speech-related NMR sites will be helpful in surgical planning and intraoperative mapping and provide in-depth insight into the motor control of speech production.

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

BACKGROUND: 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.

Stereotactic probability and variability of speech arrest and anomia sites during stimulation mapping of the language dominant hemisphere.

OBJECTIVE Functional mapping using direct cortical stimulation is the gold standard for the prevention of postoperative morbidity during resective surgery in dominant-hemisphere perisylvian regions. Its role is necessitated by the significant interindividual variability that has been observed for essential language sites. The aim in this study was to determine the statistical probability distribution of eliciting aphasic errors for any given stereotactically based cortical position in a patient cohort and to quantify the variability at each cortical site. METHODS Patients undergoing awake craniotomy for dominant-hemisphere primary brain tumor resection between 1999 and 2014 at the authors' institution were included in this study, which included counting and picture-naming tasks during dense speech mapping via cortical stimulation. Positive and negative stimulation sites were collected using an intraoperative frameless stereotactic neuronavigation system and were converted to Montreal Neurological Institute coordinates. Data were iteratively resampled to create mean and standard deviation probability maps for speech arrest and anomia. Patients were divided into groups with a "classic" or an "atypical" location of speech function, based on the resultant probability maps. Patient and clinical factors were then assessed for their association with an atypical location of speech sites by univariate and multivariate analysis. RESULTS Across 102 patients undergoing speech mapping, the overall probabilities of speech arrest and anomia were 0.51 and 0.33, respectively. Speech arrest was most likely to occur with stimulation of the posterior inferior frontal gyrus (maximum probability from individual bin = 0.025), and variance was highest in the dorsal premotor cortex and the posterior superior temporal gyrus. In contrast, stimulation within the posterior perisylvian cortex resulted in the maximum mean probability of anomia (maximum probability = 0.012), with large variance in the regions surrounding the posterior superior temporal gyrus, including the posterior middle temporal, angular, and supramarginal gyri. Patients with atypical speech localization were far more likely to have tumors in canonical Broca's or Wernicke's areas (OR 7.21, 95% CI 1.67-31.09, p < 0.01) or to have multilobar tumors (OR 12.58, 95% CI 2.22-71.42, p < 0.01), than were patients with classic speech localization. CONCLUSIONS This study provides statistical probability distribution maps for aphasic errors during cortical stimulation mapping in a patient cohort. Thus, the authors provide an expected probability of inducing speech arrest and anomia from specific 10-mm2 cortical bins in an individual patient. In addition, they highlight key regions of interindividual mapping variability that should be considered preoperatively. They believe these results will aid surgeons in their preoperative planning of eloquent cortex resection.

Mapeo del lenguaje utilizando estimulación magnética transcraneal repetitiva por navegación: un estudio comparativo con la estimulación cortical directa intraoperatoria / Language mapping using repetitive transcranial magnetic stimulation by navigation: a comparative study with direct intraoperative cortical stimulation

Introducción: la estimulación cortical directa (DCS) es una metodología corrientemente usada para localizar áreas del lenguaje en intervenciones quirúrgicas que incluyan resecciones.La estimulación magnética transcraneana repetitiva (rTMS) a demostrado también su capacidad para inducir alteraciones transitorias. Recientemente el desarrollo del Sistema de Navegación de TMS asegura precisa localización del sitio estimulado. El objetivo del trabajo es estudiar la confiabilidad de la estimulación magnética transcraneal repetitiva navegada (nrTMS) en la localización de los sitios del lenguaje. Métodos: Once pacientes seleccionados para mapeo del lenguaje por DCS fueron evaluados pre-cirugía con nrTMS. Los mapeos de lenguaje prequirúrgicos mediante nrTMS fueron comparados con DCS. Resultados: Un total de 25 nrTMS sitios del lenguaje y 38 DCS fueron localizados. La sensibilidad y la especificidad obtenida fue de 88.4 y 95.6, respectivamente. La distancia media fue evaluada en 4,5mm. Conclusiones: Los dispositivos de nrTMS permiten la identificación de las áreas corticales del lenguaje. Con un alto grado de concordancia con el mapeo TMS. La nrTMS se muestra como una herramienta de interés en la investigación y aplicación práctica en la función del lenguaje.

Introduction: direct cortical stimulation (DCS) is currently used to localise language areas in surgical resections. Repetitive transcranial magnetic stimulation (rTMS) has also shown its capacity to induce transient language alterations. Newly developed Navigated Brain Systems of TMS ensure precise topographical localisation of the stimulated site. The objective was to study the reliability of navigated repetitive transcranial magnetic stimulation (nrTMS) in language sites localisation.Methods: Eleven patients selected for DCS language mapping were presurgically evaluated with nrTMS. These presurgicalnrTMS language maps were then compared with DCS.Results: A total number of 25 nrTMS and 38 DCS language sites were localised. Sensitivity and specificity were calculated as 88.4 and 95.6 respectively. Mean distance was assessed as 4.5 millimetres. Conclusions: nrTMS devices allow identification of cortical language areas, with a high degree of concordance to TMS mapping. NrTMS shows up as an interesting tool for research and practical application in language function.