Transient selective aphasia in highly proficient bilinguals triggered by electrical stimulation of the left superior temporal gyrus

Transient selective aphasia in highly proficient bilinguals triggered by electrical stimulation of the left superior temporal gyrus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Transient selective aphasia in highly proficient bilinguals triggered by electrical stimulation of the left superior temporal gyrus Ileana Quiñones, Sandra Gisbert-Muñoz, Garazi Bermudez, Iñigo Pomposo, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5951755/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Apr, 2025 Read the published version in Acta Neurochirurgica → Version 1 posted 6 You are reading this latest preprint version Abstract Are an individual’s first (L1) and second (L2) languages represented in shared or distinct brain territories? Using intraoperative electrical stimulation mapping (ESM) in two Basque-Spanish bilinguals with non-growing lesions—thus avoiding confounding effects of adaptive plasticity—this study identified distinct language representations within the left temporal lobe. Stimulation of posterior and anterior superior temporal gyri induced language-selective aphasias, whereas stimulation of the mid-temporal region and inferior fronto-occipital fasciculus produced naming errors without language specificity. These findings highlight both shared and distinct loci for L1 and L2, advancing our understanding of bilingual brain organization. bilingualism left superior temporal gyrus direct electrical stimulation Figures Figure 1 Figure 2 Figure 3 Figure 4 Highlights 1. Stimulation of the left STG triggers selective aphasia in highly proficient bilinguals. 2. Direct electrical stimulation reveals both shared and language-specific areas for L1 and L2. 3. Stimulation of the left MTG and the IFOF shows common sites for L1 and L2. Introduction Mapping the locus of both first (L1) and second (L2) language representation in the bilingual brain has long fascinated researchers. Central to this inquiry lies a longstanding yet unresolved question: Do languages inhabit shared or distinct neural territories? This debate has spurred extensive research ( 1 ), yielding mixed findings. Some studies show significant L1-L2 overlap ( 2, 3 ), suggesting a common neural landscape, while others ( 4 ) identify discrete brain regions dedicated to each language. Recently, intraoperative electrical stimulation mapping (ESM) during awake brain surgeries has proven effective for localizing language areas in bilingual patients ( 5, 6 ). However, infiltrating lesions (e.g., brain tumors) often induce functional reorganization ( 7, 8 ), complicating efforts to pinpoint the “putative” neural signatures of L1 and L2. Here, we examined language representation in two highly proficient Basque-Spanish bilinguals, with similar multilingual exposure and daily language-switching. Both harbored small benign left temporal lobe lesions. Unlike prior ESM studies involving bilinguals with infiltrating brain tumors ( 6, 9 ), our patients had “neurotypical” brains, free from tumor-driven reorganization. This unique opportunity allowed us to examine L1 and L2 production in early (< 3 years) bilinguals who used both languages interchangeably. Despite lesion location differences, surgical resection followed a similar approach, revealing overlapping regions of functional stimulation alongside the temporal lobe. By combining a bilingual picture-naming task with online ESM, we functionally mapped cortico-subcortical language pillars across L1 and L2, identifying structure-to-function relationships in neural tissue unaffected by adaptive plasticity. Materials and Methods Clinical Cases. The study involved two highly proficient, right-handed individuals fluent in both Basque and Spanish, actively contributing to professional roles in a multilingual environment. Case 1 revolves around a 33-year-old woman who sought medical consultation for a persistent headache exacerbated by recumbency. A subsequent diagnosis revealed an incidental left temporomesial cavernoma. Case 2 involves a 23-year-old male diagnosed with a BRAF-mutated grade I dysembryoplastic neuroepithelial tumor (DNET), presenting with drug-resistant epilepsy five years prior (see Table 1 and Fig. 1 ). Table 1 Characterization of the clinical cases. Case 1 Case 2 Age 33 23 Biological sex female male Educational level (years) 18 14 L1/L2 proficiency 100/100 100/100 L1/L2 age of acquisition 0/0 0/3 Daily L1/L2 exposure 60/40 60/40 Lesion volume (cm 3 ) 3.59 2.37 Language proficiency was measured using the Basque, English, and Spanish picture-naming standardized tests [BEST] (Bruin et al., 2017). Daily exposure to both languages was estimated by asking them to rate the percentage of time spent per day listening, speaking, reading, and writing in Basque and Spanish. Ratings were averaged to obtain a self-rating composite score. Intraoperative Functional Mapping. Resective awake brain surgery was performed under the asleep-awake-asleep protocol for Case 1 and under conscious sedation with dexmedetomidine for Case 2. Intraoperative functional mapping was conducted using cortical and subcortical stimulation at 60 Hz, delivered with human-use certified intraoperative equipment (NimEclipse®, Medtronic). The entry point was determined through cortical stimulation, while subcortical stimulation was applied at specific functional limits. Positive functional responses were identified by the involuntary cessation (i.e., speech arrest) of counting during stimulation, as detailed in previous studies ( 10 ). Different aspects of language processing (i.e., phonological, lexico-semantic, and syntactic) were assessed through a bilingual sentence completion task (see Fig. 2 ). Cluster Analysis. During intraoperative stimulation, neurosurgeons mark sites as positive stimulation or eloquent areas if a behavioral change occurs two out of three times. However, due to the technique’s complexity, it is not feasible to quantify the replicability of the results in real-time. To address this issue and estimate the replicability of significant effects during stimulation both within and between individuals, a neighborhood-based clustering approach was employed. Results Intraoperative Functional Mapping. The intensity of the electrical stimulation was initially calibrated at the cortical level in the inferior ventral pre/motor cortex using a number counting task. In both clinical cases, positive responses (i.e., speech arrest) were evoked at the base of the premotor cortex. For bilingual language mapping, a total of 216 experimental trials were used from which positive stimulation points were identified and labeled based on the type of behavioral change observed. Specifically, four types of behavioral impairments became evident: the most frequent was anomia (77.22% of the positive trials), followed by dysarthria (12.66%), semantic paraphasias (8.86%), and one instance of a language switch error (1.27%), which could not be replicated (see Fig. 3 ). Specifically, in Case 1, three responsive regions were found. The first, located in the posterior segment of the left STG near the supramarginal gyrus, produced L2-specific anomias and semantic paraphasias (red dots in Fig. 4 ). The second, situated in the posterior part of the left MTG, captured anomias without language specificity (orange dots in Fig. 4 ). Subcortically, a third region was identified within the left IFOF (blue dots in Fig. 4 ), inducing anomias, semantic paraphasias, and one non-replicable language switch error. In Case 2, we identified three regions. The first, located in the anterior part of the STG, induced L1-specific anomias (yellow dots in Fig. 4 ). The second, at the anterior segment of the MTG, resulted in anomias and dysarthria in both languages (green dots in Fig. 4 ). The third, located in the anterior segment of the left IFOF, elicited anomias and dysarthria in both languages (violet dots in Fig. 4 ). Overall, in both patients, cortical stimulation of the medial segments of the STG and MTG did not produce any behavioral changes in either language. At the subcortical level, both patients exhibited similar behavioral responses inducing naming errors with no language-specific distinctions. Coordinates of both cortical and subcortical positive stimulation points were further included in the neighborhood-based approach based on k-means clustering algorithm (see Table S1 and Fig. S1 ). At the cortical level, the algorithm identified four clusters largely overlapping with the regions identified during the surgery. However, at the subcortical level, although three distinct regions were identified during the surgery, the cluster analysis grouped the data into only two clusters both located within the posterior segment of the left IFOF (see Fig. 4 ). Postoperative Clinical Assessment. After surgery, the patient referred to as Case 1 experienced mild transient dysphasia in both L1 and L2, characterized by normal verbal comprehension but difficulties with lexical retrieval. However, the three-month postoperative neuropsychological assessment revealed no cognitive impairments. In Case 2, there was no neurological impairment following surgery, and no further seizures were observed during a five-year follow-up period. Discussion In this study, we mapped L1 and L2 representation along cortical and subcortical regions of the left temporal lobe in two highly proficient bilinguals, revealing both shared and language-specific sites. ESM targeting the left STG—a key region involved in control monitoring during speech production—elicited selective aphasia-like symptoms in either L1 or L2, experimentally validating clinical instances of this condition. Conversely, stimulation of the left MTG and the IFOF—primarily involved in lexical-semantic processing—revealed common language sites. Although anomia was the most frequent error, we also found a functional anterior-posterior dissociation: posterior stimulation produced semantic paraphasias, whereas anterior stimulation caused dysarthria. These findings are discussed in detail below 1 . Evidence for language-specific microcircuits within the left STG. Since Wernicke’s seminal work in 1974, the left STG has been recognized as central to speech perception and production ( 13 ). In our study, ESM over the left STG resulted in aphasic-like symptoms (i.e., word-retrieval difficulties) during a sentence completion task requiring overt picture naming. This aligns with evidence from aphasic patients linking anomia to atrophy in both anterior and posterior segments of the left STG ( 14 ). Likewise, previous ESM studies in tumor patients ( 15, 16 ), show that anomia can be elicited via stimulation of the left STG, reinforcing its critical role in speech production. A key finding, however, was the localization of distinct sites for L1 and L2 errors within the STG. Contrary to accounts of overlapping L1–L2 representation in highly proficient individuals ( 2, 3 ), our results provide direct ESM evidence of language-specific effects. This suggests that, even in early, highly proficient bilinguals, the network supporting language production exhibits language-dependent variations at the microcircuit level in the left STG (see Fig. S2). Further, it underscores how MRI, though invaluable for mapping broad neural networks, may miss fine-grained functional organization within language areas (see 17 for evidence supporting the microcellular arrangement of the STG ). Evidence for overlapping L1 and L2 representation along the left MTG. Two positive-stimulation clusters emerged along the left MTG, where ESM triggered transient anomia with no language specificity. Interestingly, a recent meta-analysis of lesion-symptom mapping studies ( 18 ) highlights this region's critical involvement in the early stage of word production, namely during lexico-semantic retrieval. Furthermore, evidence shows that, even after controlling for visual and motor-speech deficits in chronic stroke patients, only the left mid-posterior MTG and its adjacent white matter area were significantly linked to performance in picture naming ( 19 ). Additionally, our findings in the left MTG mirrored the gradient observed along the STG, with posterior MTG stimulation producing semantic paraphasias and anterior stimulation resulting in dysarthria. While posterior MTG are involved in lexico-semantic aspects of word retrieval, more anterior regions contribute to sentence-level processing and integrating lexico-semantic and grammatical information ( 20 ). Given that our sentence-completion task required number and gender agreement, disrupting this combinatorial process likely explains the observed effects. Overall, these findings underscore the left MTG’s pivotal role in integrating and producing fluent speech, irrespective of the language in use. [1] See also the Supplementary Material for additional considerations. Conclusions These findings highlight the coexistence of shared and distinct regions for language production, depending on the linguistic processes engaged. Clinically, this underscores the importance of personalized care that accounts for both linguistic and neural uniqueness. Understanding bilingual brain organization, both pre- and intraoperatively, is crucial for fully preserving all spoken languages. Declarations Funding This research was supported by the Ikerbasque Foundation; by the Basque Government through the BERC 2022-2025 program; by the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation SEV CEX2020-001010-S, the Ramon y Cajal Fellowships RYC2022-035514-I (LA), and RYC2022-035533-I (IQ), the Spanish Ministry of Economy and Competitiveness through the Plan Nacional PID2021-123575OB-I00 (SCANCER) to LA, the Spanish Health Institute Carlos III through the Strategic Action in Health (PI24/00948) to IQ, the Health Department of the Basque Government through the project 2021333011 to IP, and by “la Caixa” Foundation (ID 100010434), under the agreement HR18-00178-DYSTHAL granted to MC, and co-funded by the European Union. We would like to thank BCBL’s Lab Department, in particular David Carcedo and Maite Kalzakorta, who have been working with us during the data recording process. Conflicts of interest/Competing interests The authors declare no conflict of interest. Availability of data and material The data presented in this study as well as the cognitive tasks and experimental stimuli used during the surgery are available on request from the corresponding author. The data are not publicly available due to the data-sharing policies of the different institutions involved. Code availability Not applicable Authors’ contributions Conceptualization: I.Q., L.A., M.C.; Methodology: I.Q., L.A., S.G., G.B., S.G.R., and I.P.; Software: I.Q.; Formal analysis: I.Q., S.G., L.A. and G.B; Investigation: I.Q., L.A., S.G., and G.B.; Resources, I.Q., M.C., L.A., and I.P.; Data curation: I.Q., S.G., and G.B.; Writing—original draft preparation: I.Q., SG, and L.A.; Writing—review and editing: I.Q., S.G., L.A., S.G.R., and M.C.; Visualization: I.Q.; Supervision: I.Q., M.C., and L.A.; Project administration: I.Q., L.A., M.C., and I.P.; Funding acquisition: I.Q., L.A., M.C., and I.P. All authors have read and agreed to the published version of the manuscript. Ethical approval The study was conducted under the Declaration of Helsinki and approved by the BCBL Ethics Committee and the Euskadi Ethics Committee for Clinical Research (protocol code: PI2017002). Human Ethics and Consent to Participate Declarations The study was performed following the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Additionally, this case study was approved by the BCBL Ethics Committee and the Euskadi Ethics Committee for Clinical Research (protocol code: PI2017002). Informed consent was obtained from both participants included in the study. This consent covered the recording of neuroimaging and behavioral responses before, during, and after surgery, as well as the collection of images and voice recordings. To maintain anonymity, both voice and facial features have been intentionally distorted. References M. Paradis, A Neurolinguistic theory of bilingualism . (John Benjamins Publishing Company, Amsterdam, 2004). D. Perani et al. , The bilingual brain. Proficiency and age of acquisition of the second language. Brain : a journal of neurology 121 ( Pt 10) , 1841-1852 (1998). D. Klein, B. Milner, R. J. Zatorre, E. Meyer, A. C. Evans, The neural substrates underlying word generation: a bilingual functional-imaging study. Proceedings of the National Academy of Sciences of the United States of America 92 , 2899-2903 (1995). P. Indefrey, A meta-analysis of hemodynamic studies on first and second language processing: Which suggested differences can we trust and what do they mean? Language Learning 56 , 279–304 (2006). V. Lubrano, K. Prod’homme, J. Démonet, B. Köpke, Language monitoring in multilingual patients undergoing awake craniotomy: A case study of a German–English–French trilingual patient with a WHO grade II glioma. Journal of Neurolinguistics , 1-12 (2011). C. Giussani, F. E. Roux, V. Lubrano, S. M. Gaini, L. Bello, Review of language organisation in bilingual patients: what can we learn from direct brain mapping? Acta neurochirurgica 149 , 1109-1116; discussion 1116 (2007). L. E. van Dokkum et al. , Resting state network plasticity related to picture naming in low-grade glioma patients before and after resection. NeuroImage. Clinical 24 , 102010 (2019). H. Duffau, The huge plastic potential of adult brain and the role of connectomics: new insights provided by serial mappings in glioma surgery. Cortex 58 , 325-337 (2014). F. E. Roux, M. Tremoulet, Organization of language areas in bilingual patients: a cortical stimulation study. Journal of neurosurgery 97 , 857-864 (2002). E. Mandonnet, S. Sarubbo, H. Duffau, Proposal of an optimized strategy for intraoperative testing of speech and language during awake mapping. Neurosurgical review 40 , 29-35 (2017). S. Gisbert-Munoz et al. , MULTIMAP: Multilingual picture naming test for mapping eloquent areas during awake surgeries. Behavior research methods 53 , 918-927 (2021). M. Xia, J. Wang, Y. He, BrainNet Viewer: A Network Visualization Tool for Human Brain Connectomics. PloS one 8 , e68910-e68910. (2013). B. R. Buchsbaum, M. D'Esposito, The search for the phonological store: from loop to convolution. Journal of cognitive neuroscience 20 , 762-778 (2008). D. R. Akhmadullina, R. N. Konovalov, Y. A. Shpilyukova, E. Y. Fedotova, S. N. Illarioshkin, Anomia: Deciphering Functional Neuroanatomy in Primary Progressive Aphasia Variants. Brain sciences 13 , (2023). E. Collee et al. , Localization patterns of speech and language errors during awake brain surgery: a systematic review. Neurosurgical review 46 , 38 (2023). S. Sarubbo et al. , Mapping critical cortical hubs and white matter pathways by direct electrical stimulation: an original functional atlas of the human brain. NeuroImage 205 , 116237 (2020). A. M. Chan et al. , Speech-specific tuning of neurons in human superior temporal gyrus. Cerebral Cortex 24 , 2679-2693 (2014). V. Piai, D. Eikelboom, Brain Areas Critical for Picture Naming: A Systematic Review and Meta-Analysis of Lesion-Symptom Mapping Studies. Neurobiol Lang (Camb) 4 , 280-296 (2023). J. V. Baldo, A. Arevalo, J. P. Patterson, N. F. Dronkers, Grey and white matter correlates of picture naming: evidence from a voxel-based lesion analysis of the Boston Naming Test. Cortex; a journal devoted to the study of the nervous system and behavior 49 , 658-667 (2013). J. Brennan, L. Pylkkänen, The time-course and spatial distribution of brain activity associated with sentence processing. NeuroImage 60 , 1139-1148 (2012). Additional Declarations No competing interests reported. Supplementary Files SUPLEMENTARYINFORMATION.docx Cite Share Download PDF Status: Published Journal Publication published 05 Apr, 2025 Read the published version in Acta Neurochirurgica → Version 1 posted Editorial decision: Accepted 30 Mar, 2025 Reviews received at journal 27 Mar, 2025 Reviewers agreed at journal 27 Mar, 2025 Reviewers invited by journal 26 Mar, 2025 Submission checks completed at journal 26 Mar, 2025 First submitted to journal 26 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5951755","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":434513354,"identity":"9fc6e509-77c5-4d0f-bb8b-b47f8e637a14","order_by":0,"name":"Ileana Quiñones","email":"data:image/png;base64,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","orcid":"","institution":"Biogipuzkoa Health Research Institute","correspondingAuthor":true,"prefix":"","firstName":"Ileana","middleName":"","lastName":"Quiñones","suffix":""},{"id":434513355,"identity":"863e3274-84b0-4b76-9a41-76c8f71cc661","order_by":1,"name":"Sandra Gisbert-Muñoz","email":"","orcid":"","institution":"EIC Business and Marketing School","correspondingAuthor":false,"prefix":"","firstName":"Sandra","middleName":"","lastName":"Gisbert-Muñoz","suffix":""},{"id":434513356,"identity":"9f9fed1f-878b-407c-97bf-53bb38816c96","order_by":2,"name":"Garazi Bermudez","email":"","orcid":"","institution":"BioCruces Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Garazi","middleName":"","lastName":"Bermudez","suffix":""},{"id":434513357,"identity":"02e71a33-a0b1-4e48-a4a3-e04e1e5e492d","order_by":3,"name":"Iñigo Pomposo","email":"","orcid":"","institution":"BioCruces Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Iñigo","middleName":"","lastName":"Pomposo","suffix":""},{"id":434513358,"identity":"a9e16e8d-008b-4fbb-b881-427113ad0e2d","order_by":4,"name":"Santiago Gil Robles","email":"","orcid":"","institution":"BioCruces Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Santiago","middleName":"Gil","lastName":"Robles","suffix":""},{"id":434513359,"identity":"e948bb43-9251-4178-b40f-fdef8ea52206","order_by":5,"name":"Manuel Carreiras","email":"","orcid":"","institution":"BCBL. Basque Center on Cognition, Brain, and Language, 20009, San Sebastian","correspondingAuthor":false,"prefix":"","firstName":"Manuel","middleName":"","lastName":"Carreiras","suffix":""},{"id":434513360,"identity":"f02bd8ef-c394-4861-907e-d0a0632bea2b","order_by":6,"name":"Lucia Amoruso","email":"","orcid":"","institution":"BCBL. Basque Center on Cognition, Brain, and Language, 20009, San Sebastian","correspondingAuthor":false,"prefix":"","firstName":"Lucia","middleName":"","lastName":"Amoruso","suffix":""}],"badges":[],"createdAt":"2025-02-03 14:23:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5951755/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5951755/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00701-025-06508-5","type":"published","date":"2025-04-05T15:57:57+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79331969,"identity":"2474a80d-0b95-4e44-9220-edc9404fdf6b","added_by":"auto","created_at":"2025-03-27 06:50:49","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":245190,"visible":true,"origin":"","legend":"\u003cp\u003eImaging characterization of the two clinical cases using a 3T Siemens Magnetom Prisma Fit scanner (Siemens AG, Erlangen, Germany). The upper left panel for each case displays the exposed cortical surface, revealing normal anatomy with no visible pathological signs. The upper right panel highlights the lesion location in red. The lower panel presents pre-surgical tractography reconstructions for both patients, illustrating the tracts adjacent to the lesion. Cavernoma resection in Case 1 followed a transcortical approach along the inferior temporal gyrus, involving the opening of the posterior part of the temporal horn of the lateral ventricle. For Case 2, DNET resection was conducted around the STG, between the superior and medial temporal gyri, up to the lateralmost wall of the sagittal striatum. Points associated with behavioral changes were marked as positive stimulation sites. For Case 1, the reconstructed tracts include the left IFOF and the Inferior Longitudinal Fasciculus (ILF). For Case 2, the tracts adjacent to the lesion are the IFOF and the Arcuate Fasciculus. Tracts are mapped onto T1-weighted images of each subject. The left side of the panel shows an axial view, while the right side provides a sagittal view. The axial view in the center of the panel includes black crosses indicating points where subcortical electrical stimulation was applied (see Supplementary Material for more details).\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5951755/v1/aa88e06d84d3985489c20bbf.jpeg"},{"id":79331977,"identity":"7cfc41e2-8ff7-4db4-a84a-3172d3ca3a04","added_by":"auto","created_at":"2025-03-27 06:50:50","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":199464,"visible":true,"origin":"","legend":"\u003cp\u003eExperimental Protocol. (A) Examples of the images used during the language production task. These images were pre-validated to ensure hit levels above 85% (\u003cem\u003e11\u003c/em\u003e). (B) Recording process during intraoperative stimulation. Continuous audio-visual recordings of the surgical procedure were made while a rehabilitation physician monitored the patient's behavior. The procedure is guided by a neuronavigation system, which ensures precise localization of the stimulation coordinates throughout the surgery. A bipolar stimulation probe (Inomed, fork probe, 45 mm straight, ball tip diameter 2 mm, tip-to-tip distance 8 mm) was used at 2.5 mA. Only those sites where direct electrical stimulation-associated errors were replicated in at least 2 out of 3 non-consecutive trials were deemed as functional. The procedure lasted 4 hours and 45 minutes for Case 1 and 2 hours and 20 minutes for Case 2, with alternating periods of stimulation and rest. A total of 92 cortical and 39 subcortical points (131 in total), were respectively stimulated.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5951755/v1/aef45db7fd9e61afa5fbaf0b.jpeg"},{"id":79332799,"identity":"43f5c148-28fb-426b-8941-f934349825ad","added_by":"auto","created_at":"2025-03-27 06:58:49","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":74875,"visible":true,"origin":"","legend":"\u003cp\u003ePatients' behavior during surgeries. Data from 216 trials, where patients were required to produce a sentence based on a depicted picture, were considered. These trials include both those conducted during direct electrical stimulation periods and those during lesion traction. \u003cstrong\u003eDES:\u003c/strong\u003enumber of direct electrical stimulations performed during surgeries. Each stimulation is associated with an experimental trial where participants name images. \u003cstrong\u003eSurgical Traction:\u003c/strong\u003e experimental trials conducted during lesion removal. \u003cstrong\u003eNo DES:\u003c/strong\u003e control trials where patients named images without stimulation. The total number of trials used varied for each patient, directly correlating with the duration of their surgeries.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5951755/v1/73c22bd0c6dd46d590f2e1e0.jpeg"},{"id":79331975,"identity":"6a27cfe8-4457-462f-9c39-4c075bb60b0d","added_by":"auto","created_at":"2025-03-27 06:50:50","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":381953,"visible":true,"origin":"","legend":"\u003cp\u003eESM of the left temporal cortex and adjacent white matter tracts. The cortical mapping includes the STG, MTG, and the inferior temporal gyrus. A) Positive and negative stimulation points are superimposed on a surface reconstructed from template BrainMesh_ICBM152Left.nv. The left panel shows cortical positive stimulation points, while the right panel displays subcortical positive stimulation points. The graphs were made using BrainNet Viewer, a brain network visualization tool designed by Xia, Wang and He (\u003cem\u003e12\u003c/em\u003e). B) Cluster analysis based on the stimulated coordinates (see Supplementary Materials for more details), resulting in six distinct clusters, each represented by a different color. At the cortical level, the algorithm identified four: posterior STG (cluster 1, MNI coordinates of the centroid [x, y, z]: -59, -45, 20), anterior STG (cluster 2, centroid: -59, -2, -2), posterior MTG (cluster 3, centroid: -59, -35, 0), and anterior MTG (cluster 4, centroid: -55 -16 -8). At the subcortical level, the cluster analysis grouped the data into only two clusters both located within the posterior segment of the left IFOF (clusters 5, centroid: -39, -43, -8; and 6, centroid: -45, -13, -13).\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5951755/v1/2f887617d3f50a856fc55e6f.jpeg"},{"id":80082282,"identity":"9eeb1aae-2b4f-4239-994f-894cc57a8c00","added_by":"auto","created_at":"2025-04-07 16:08:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1434993,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5951755/v1/85b90a28-8ed0-491a-8ed6-3b3c5d71173f.pdf"},{"id":79331972,"identity":"ec1da767-9b47-444b-b394-f1ecaee747fd","added_by":"auto","created_at":"2025-03-27 06:50:50","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":488484,"visible":true,"origin":"","legend":"","description":"","filename":"SUPLEMENTARYINFORMATION.docx","url":"https://assets-eu.researchsquare.com/files/rs-5951755/v1/3d7a339d4f34b02a91d8f1a1.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Transient selective aphasia in highly proficient bilinguals triggered by electrical stimulation of the left superior temporal gyrus","fulltext":[{"header":"Highlights","content":"\u003cp\u003e1. Stimulation of the left STG triggers selective aphasia in highly proficient bilinguals.\u003c/p\u003e\n\u003cp\u003e2. Direct electrical stimulation reveals both shared and language-specific areas for L1 and L2.\u003c/p\u003e\n\u003cp\u003e3. Stimulation of the left MTG and the IFOF shows common sites for L1 and L2.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eMapping the \u003cem\u003elocus\u003c/em\u003e of both first (L1) and second (L2) language representation in the bilingual brain has long fascinated researchers. Central to this inquiry lies a longstanding yet unresolved question: Do languages inhabit shared or distinct neural territories? This debate has spurred extensive research (\u003cem\u003e1\u003c/em\u003e), yielding mixed findings. Some studies show significant L1-L2 overlap (\u003cem\u003e2, 3\u003c/em\u003e), suggesting a common neural landscape, while others (\u003cem\u003e4\u003c/em\u003e) identify discrete brain regions dedicated to each language. Recently, intraoperative electrical stimulation mapping (ESM) during awake brain surgeries has proven effective for localizing language areas in bilingual patients (\u003cem\u003e5, 6\u003c/em\u003e). However, infiltrating lesions (e.g., brain tumors) often induce functional reorganization (\u003cem\u003e7, 8\u003c/em\u003e), complicating efforts to pinpoint the \u0026ldquo;putative\u0026rdquo; neural signatures of L1 and L2.\u003c/p\u003e \u003cp\u003eHere, we examined language representation in two highly proficient Basque-Spanish bilinguals, with similar multilingual exposure and daily language-switching. Both harbored small benign left temporal lobe lesions. Unlike prior ESM studies involving bilinguals with infiltrating brain tumors (\u003cem\u003e6, 9\u003c/em\u003e), our patients had \u0026ldquo;neurotypical\u0026rdquo; brains, free from tumor-driven reorganization. This unique opportunity allowed us to examine L1 and L2 production in early (\u0026lt;\u0026thinsp;3 years) bilinguals who used both languages interchangeably. Despite lesion location differences, surgical resection followed a similar approach, revealing overlapping regions of functional stimulation alongside the temporal lobe. By combining a bilingual picture-naming task with online ESM, we functionally mapped cortico-subcortical language pillars across L1 and L2, identifying structure-to-function relationships in neural tissue unaffected by adaptive plasticity.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e \u003cem\u003eClinical Cases.\u003c/em\u003e The study involved two highly proficient, right-handed individuals fluent in both Basque and Spanish, actively contributing to professional roles in a multilingual environment. Case 1 revolves around a 33-year-old woman who sought medical consultation for a persistent headache exacerbated by recumbency. A subsequent diagnosis revealed an incidental left temporomesial cavernoma. Case 2 involves a 23-year-old male diagnosed with a BRAF-mutated grade I dysembryoplastic neuroepithelial tumor (DNET), presenting with drug-resistant epilepsy five years prior (see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacterization of the clinical cases.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCase 2\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiological sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003efemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003emale\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducational level (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL1/L2 proficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100/100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100/100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL1/L2 age of acquisition\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDaily L1/L2 exposure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60/40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60/40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLesion volume (cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eLanguage proficiency was measured using the Basque, English, and Spanish picture-naming standardized tests [BEST] (Bruin et al., 2017). Daily exposure to both languages was estimated by asking them to rate the percentage of time spent per day listening, speaking, reading, and writing in Basque and Spanish. Ratings were averaged to obtain a self-rating composite score.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eIntraoperative Functional Mapping.\u003c/em\u003e Resective awake brain surgery was performed under the asleep-awake-asleep protocol for Case 1 and under conscious sedation with dexmedetomidine for Case 2. Intraoperative functional mapping was conducted using cortical and subcortical stimulation at 60 Hz, delivered with human-use certified intraoperative equipment (NimEclipse\u0026reg;, Medtronic). The entry point was determined through cortical stimulation, while subcortical stimulation was applied at specific functional limits. Positive functional responses were identified by the involuntary cessation (i.e., speech arrest) of counting during stimulation, as detailed in previous studies (\u003cem\u003e10\u003c/em\u003e). Different aspects of language processing (i.e., phonological, lexico-semantic, and syntactic) were assessed through a bilingual sentence completion task (see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cem\u003eCluster Analysis.\u003c/em\u003e During intraoperative stimulation, neurosurgeons mark sites as positive stimulation or eloquent areas if a behavioral change occurs two out of three times. However, due to the technique\u0026rsquo;s complexity, it is not feasible to quantify the replicability of the results in real-time. To address this issue and estimate the replicability of significant effects during stimulation both within and between individuals, a neighborhood-based clustering approach was employed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cem\u003eIntraoperative Functional Mapping.\u003c/em\u003e The intensity of the electrical stimulation was initially calibrated at the cortical level in the inferior ventral pre/motor cortex using a number counting task. In both clinical cases, positive responses (i.e., speech arrest) were evoked at the base of the premotor cortex. For bilingual language mapping, a total of 216 experimental trials were used from which positive stimulation points were identified and labeled based on the type of behavioral change observed. Specifically, four types of behavioral impairments became evident: the most frequent was anomia (77.22% of the positive trials), followed by dysarthria (12.66%), semantic paraphasias (8.86%), and one instance of a language switch error (1.27%), which could not be replicated (see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSpecifically, in Case 1, three responsive regions were found. The first, located in the posterior segment of the left STG near the supramarginal gyrus, produced L2-specific anomias and semantic paraphasias (red dots in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The second, situated in the posterior part of the left MTG, captured anomias without language specificity (orange dots in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Subcortically, a third region was identified within the left IFOF (blue dots in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), inducing anomias, semantic paraphasias, and one non-replicable language switch error. In Case 2, we identified three regions. The first, located in the anterior part of the STG, induced L1-specific anomias (yellow dots in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The second, at the anterior segment of the MTG, resulted in anomias and dysarthria in both languages (green dots in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The third, located in the anterior segment of the left IFOF, elicited anomias and dysarthria in both languages (violet dots in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Overall, in both patients, cortical stimulation of the medial segments of the STG and MTG did not produce any behavioral changes in either language. At the subcortical level, both patients exhibited similar behavioral responses inducing naming errors with no language-specific distinctions.\u003c/p\u003e \u003cp\u003eCoordinates of both cortical and subcortical positive stimulation points were further included in the neighborhood-based approach based on k-means clustering algorithm (see Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e and Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). At the cortical level, the algorithm identified four clusters largely overlapping with the regions identified during the surgery. However, at the subcortical level, although three distinct regions were identified during the surgery, the cluster analysis grouped the data into only two clusters both located within the posterior segment of the left IFOF (see Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e\u003cem\u003ePostoperative Clinical Assessment.\u003c/em\u003e After surgery, the patient referred to as Case 1 experienced mild transient dysphasia in both L1 and L2, characterized by normal verbal comprehension but difficulties with lexical retrieval. However, the three-month postoperative neuropsychological assessment revealed no cognitive impairments. In Case 2, there was no neurological impairment following surgery, and no further seizures were observed during a five-year follow-up period.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we mapped L1 and L2 representation along cortical and subcortical regions of the left temporal lobe in two highly proficient bilinguals, revealing both shared and language-specific sites. ESM targeting the left STG\u0026mdash;a key region involved in control monitoring during speech production\u0026mdash;elicited selective aphasia-like symptoms in either L1 or L2, experimentally validating clinical instances of this condition. Conversely, stimulation of the left MTG and the IFOF\u0026mdash;primarily involved in lexical-semantic processing\u0026mdash;revealed common language sites. Although anomia was the most frequent error, we also found a functional anterior-posterior dissociation: posterior stimulation produced semantic paraphasias, whereas anterior stimulation caused dysarthria. These findings are discussed in detail below\u003ca href=\"#_ftn1\" name=\"_ftnref1\" title=\"\"\u003e\u003c/a\u003e\u003csup\u003e1\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEvidence for language-specific microcircuits within the left STG.\u0026nbsp;\u003c/em\u003eSince Wernicke\u0026rsquo;s seminal work in 1974, the left STG has been recognized as central to speech perception and production (\u003cem\u003e13\u003c/em\u003e). In our study, ESM over the left STG resulted in aphasic-like symptoms (i.e., word-retrieval difficulties) during a sentence completion task requiring overt picture naming. This aligns with evidence from aphasic patients linking anomia to atrophy in both anterior and posterior segments of the left STG (\u003cem\u003e14\u003c/em\u003e). Likewise, previous ESM studies in tumor patients (\u003cem\u003e15, 16\u003c/em\u003e), show that anomia can be elicited via stimulation of the left STG, reinforcing its critical role in speech production. A key finding, however, was the localization of distinct sites for L1 and L2 errors within the STG. Contrary to accounts of overlapping L1\u0026ndash;L2 representation in highly proficient individuals (\u003cem\u003e2, 3\u003c/em\u003e), our results provide direct ESM evidence of language-specific effects. This suggests that, even in early, highly proficient bilinguals, the network supporting language production exhibits language-dependent variations at the microcircuit level in the left STG (see Fig. S2). Further, it underscores how MRI, though invaluable for mapping broad neural networks, may miss fine-grained functional organization within language areas (see \u003cem\u003e17 for evidence supporting the microcellular arrangement of the STG\u003c/em\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEvidence for overlapping L1 and L2 representation along the left MTG.\u0026nbsp;\u003c/em\u003eTwo positive-stimulation clusters emerged along the left MTG, where ESM triggered transient anomia with no language specificity. Interestingly, a recent meta-analysis of lesion-symptom mapping studies (\u003cem\u003e18\u003c/em\u003e) highlights this region\u0026apos;s critical involvement in the early stage of word production, namely during lexico-semantic retrieval. Furthermore, evidence shows that, even after controlling for visual and motor-speech deficits in chronic stroke patients, only the left mid-posterior MTG and its adjacent white matter area were significantly linked to performance in picture naming (\u003cem\u003e19\u003c/em\u003e). Additionally, our findings in the left MTG mirrored the gradient observed along the STG, with posterior MTG stimulation producing semantic paraphasias and anterior stimulation resulting in dysarthria. While posterior MTG are involved in lexico-semantic aspects of word retrieval, more anterior regions contribute to sentence-level processing and integrating lexico-semantic and grammatical information (\u003cem\u003e20\u003c/em\u003e). Given that our sentence-completion task required number and gender agreement, disrupting this combinatorial process likely explains the observed effects. Overall, these findings underscore the left MTG\u0026rsquo;s pivotal role in integrating and producing fluent speech, irrespective of the language in use.\u003c/p\u003e\n\u003cp\u003e[1] See also the Supplementary Material for additional considerations.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThese findings highlight the coexistence of shared and distinct regions for language production, depending on the linguistic processes engaged. Clinically, this underscores the importance of personalized care that accounts for both linguistic and neural uniqueness. Understanding bilingual brain organization, both pre- and intraoperatively, is crucial for fully preserving all spoken languages.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis research was supported by the Ikerbasque Foundation; by the Basque Government through the BERC 2022-2025 program; by the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation SEV CEX2020-001010-S, the Ramon y Cajal Fellowships RYC2022-035514-I (LA), and RYC2022-035533-I (IQ), the Spanish Ministry of Economy and Competitiveness through the Plan Nacional PID2021-123575OB-I00 (SCANCER) to LA, the Spanish Health Institute Carlos III through the Strategic Action in Health (PI24/00948) to IQ, the Health Department of the Basque Government through the project 2021333011 to IP, and by \u0026ldquo;la Caixa\u0026rdquo; Foundation (ID 100010434), under the agreement HR18-00178-DYSTHAL granted to MC, and co-funded by the European Union. We would like to thank BCBL\u0026rsquo;s Lab Department, in particular David Carcedo and Maite Kalzakorta, who have been working with us during the data recording process.\u003c/p\u003e\n\u003ch2\u003eConflicts of interest/Competing interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and material\u003c/h2\u003e\n\u003cp\u003eThe data presented in this study as well as the cognitive tasks and experimental stimuli used during the surgery are available on request from the corresponding author. The data are not publicly available due to the data-sharing policies of the different institutions involved.\u003c/p\u003e\n\u003ch2\u003eCode availability\u003c/h2\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch2\u003eAuthors\u0026rsquo; contributions\u003c/h2\u003e\n\u003cp\u003eConceptualization: I.Q., L.A., M.C.; Methodology: I.Q., L.A., S.G., G.B., S.G.R., and I.P.; Software: I.Q.; Formal analysis: I.Q., S.G., L.A. and G.B; Investigation: I.Q., L.A., S.G., and G.B.; Resources, I.Q., M.C., L.A., and I.P.; Data curation: I.Q., S.G., and G.B.; Writing\u0026mdash;original draft preparation: I.Q., SG, and L.A.; Writing\u0026mdash;review and editing: I.Q., S.G., L.A., S.G.R., and M.C.; Visualization: I.Q.; Supervision: I.Q., M.C., and L.A.; Project administration: I.Q., L.A., M.C., and I.P.; Funding acquisition: I.Q., L.A., M.C., and I.P. All authors have read and agreed to the published version of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eEthical approval\u003c/h2\u003e\n\u003cp\u003eThe study was conducted under the Declaration of Helsinki and approved by the BCBL Ethics Committee and the Euskadi Ethics Committee for Clinical Research (protocol code: PI2017002).\u003c/p\u003e\n\u003ch2\u003eHuman Ethics and Consent to Participate Declarations\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003e\u003cem\u003eThe\u003c/em\u003e study was performed following the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Additionally, this case study was approved by the BCBL Ethics Committee and the Euskadi Ethics Committee for Clinical Research (protocol code: PI2017002). Informed consent was obtained from both participants included in the study. This consent covered the recording of neuroimaging and behavioral responses before, during, and after surgery, as well as the collection of images and voice recordings. To maintain anonymity, both voice and facial features have been intentionally distorted.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eM. Paradis, \u003cem\u003eA Neurolinguistic theory of bilingualism\u003c/em\u003e. (John Benjamins Publishing Company, Amsterdam, 2004).\u003c/li\u003e\n\u003cli\u003eD. Perani\u003cem\u003e et al.\u003c/em\u003e, The bilingual brain. Proficiency and age of acquisition of the second language. \u003cem\u003eBrain : a journal of neurology\u003c/em\u003e \u003cstrong\u003e121 ( Pt 10)\u003c/strong\u003e, 1841-1852 (1998).\u003c/li\u003e\n\u003cli\u003eD. Klein, B. Milner, R. J. Zatorre, E. Meyer, A. C. Evans, The neural substrates underlying word generation: a bilingual functional-imaging study. \u003cem\u003eProceedings of the National Academy of Sciences of the United States of America\u003c/em\u003e \u003cstrong\u003e92\u003c/strong\u003e, 2899-2903 (1995).\u003c/li\u003e\n\u003cli\u003eP. Indefrey, A meta-analysis of hemodynamic studies on first and second language processing: Which suggested differences can we trust and what do they mean? \u003cem\u003eLanguage Learning\u003c/em\u003e \u003cstrong\u003e56\u003c/strong\u003e, 279\u0026ndash;304 (2006).\u003c/li\u003e\n\u003cli\u003eV. Lubrano, K. Prod\u0026rsquo;homme, J. D\u0026eacute;monet, B. K\u0026ouml;pke, Language monitoring in multilingual patients undergoing awake craniotomy: A case study of a German\u0026ndash;English\u0026ndash;French trilingual patient with a WHO grade II glioma. \u003cem\u003eJournal of Neurolinguistics\u003c/em\u003e, 1-12 (2011).\u003c/li\u003e\n\u003cli\u003eC. Giussani, F. E. Roux, V. Lubrano, S. M. Gaini, L. Bello, Review of language organisation in bilingual patients: what can we learn from direct brain mapping? \u003cem\u003eActa neurochirurgica\u003c/em\u003e \u003cstrong\u003e149\u003c/strong\u003e, 1109-1116; discussion 1116 (2007).\u003c/li\u003e\n\u003cli\u003eL. E. van Dokkum\u003cem\u003e et al.\u003c/em\u003e, Resting state network plasticity related to picture naming in low-grade glioma patients before and after resection. \u003cem\u003eNeuroImage. Clinical\u003c/em\u003e \u003cstrong\u003e24\u003c/strong\u003e, 102010 (2019).\u003c/li\u003e\n\u003cli\u003eH. Duffau, The huge plastic potential of adult brain and the role of connectomics: new insights provided by serial mappings in glioma surgery. \u003cem\u003eCortex\u003c/em\u003e \u003cstrong\u003e58\u003c/strong\u003e, 325-337 (2014).\u003c/li\u003e\n\u003cli\u003eF. E. Roux, M. Tremoulet, Organization of language areas in bilingual patients: a cortical stimulation study. \u003cem\u003eJournal of neurosurgery\u003c/em\u003e \u003cstrong\u003e97\u003c/strong\u003e, 857-864 (2002).\u003c/li\u003e\n\u003cli\u003eE. Mandonnet, S. Sarubbo, H. Duffau, Proposal of an optimized strategy for intraoperative testing of speech and language during awake mapping. \u003cem\u003eNeurosurgical review\u003c/em\u003e \u003cstrong\u003e40\u003c/strong\u003e, 29-35 (2017).\u003c/li\u003e\n\u003cli\u003eS. Gisbert-Munoz\u003cem\u003e et al.\u003c/em\u003e, MULTIMAP: Multilingual picture naming test for mapping eloquent areas during awake surgeries. \u003cem\u003eBehavior research methods\u003c/em\u003e \u003cstrong\u003e53\u003c/strong\u003e, 918-927 (2021).\u003c/li\u003e\n\u003cli\u003eM. Xia, J. Wang, Y. He, BrainNet Viewer: A Network Visualization Tool for Human Brain Connectomics. \u003cem\u003ePloS one\u003c/em\u003e \u003cstrong\u003e8\u003c/strong\u003e, e68910-e68910. (2013).\u003c/li\u003e\n\u003cli\u003eB. R. Buchsbaum, M. D\u0026apos;Esposito, The search for the phonological store: from loop to convolution. \u003cem\u003eJournal of cognitive neuroscience\u003c/em\u003e \u003cstrong\u003e20\u003c/strong\u003e, 762-778 (2008).\u003c/li\u003e\n\u003cli\u003eD. R. Akhmadullina, R. N. Konovalov, Y. A. Shpilyukova, E. Y. Fedotova, S. N. Illarioshkin, Anomia: Deciphering Functional Neuroanatomy in Primary Progressive Aphasia Variants. \u003cem\u003eBrain sciences\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, (2023).\u003c/li\u003e\n\u003cli\u003eE. Collee\u003cem\u003e et al.\u003c/em\u003e, Localization patterns of speech and language errors during awake brain surgery: a systematic review. \u003cem\u003eNeurosurgical review\u003c/em\u003e \u003cstrong\u003e46\u003c/strong\u003e, 38 (2023).\u003c/li\u003e\n\u003cli\u003eS. Sarubbo\u003cem\u003e et al.\u003c/em\u003e, Mapping critical cortical hubs and white matter pathways by direct electrical stimulation: an original functional atlas of the human brain. \u003cem\u003eNeuroImage\u003c/em\u003e \u003cstrong\u003e205\u003c/strong\u003e, 116237 (2020).\u003c/li\u003e\n\u003cli\u003eA. M. Chan\u003cem\u003e et al.\u003c/em\u003e, Speech-specific tuning of neurons in human superior temporal gyrus. \u003cem\u003eCerebral Cortex\u003c/em\u003e \u003cstrong\u003e24\u003c/strong\u003e, 2679-2693 (2014).\u003c/li\u003e\n\u003cli\u003eV. Piai, D. Eikelboom, Brain Areas Critical for Picture Naming: A Systematic Review and Meta-Analysis of Lesion-Symptom Mapping Studies. \u003cem\u003eNeurobiol Lang (Camb)\u003c/em\u003e \u003cstrong\u003e4\u003c/strong\u003e, 280-296 (2023).\u003c/li\u003e\n\u003cli\u003eJ. V. Baldo, A. Arevalo, J. P. Patterson, N. F. Dronkers, Grey and white matter correlates of picture naming: evidence from a voxel-based lesion analysis of the Boston Naming Test. \u003cem\u003eCortex; a journal devoted to the study of the nervous system and behavior\u003c/em\u003e \u003cstrong\u003e49\u003c/strong\u003e, 658-667 (2013).\u003c/li\u003e\n\u003cli\u003eJ. Brennan, L. Pylkk\u0026auml;nen, The time-course and spatial distribution of brain activity associated with sentence processing. \u003cem\u003eNeuroImage\u003c/em\u003e \u003cstrong\u003e60\u003c/strong\u003e, 1139-1148 (2012).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"acta-neurochirurgica","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anch","sideBox":"Learn more about [Acta Neurochirurgica](http://link.springer.com/journal/701)","snPcode":"701","submissionUrl":"https://submission.springernature.com/new-submission/701/3","title":"Acta Neurochirurgica","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"bilingualism, left superior temporal gyrus, direct electrical stimulation","lastPublishedDoi":"10.21203/rs.3.rs-5951755/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5951755/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAre an individual\u0026rsquo;s first (L1) and second (L2) languages represented in shared or distinct brain territories? Using intraoperative electrical stimulation mapping (ESM) in two Basque-Spanish bilinguals with non-growing lesions\u0026mdash;thus avoiding confounding effects of adaptive plasticity\u0026mdash;this study identified distinct language representations within the left temporal lobe. Stimulation of posterior and anterior superior temporal gyri induced language-selective aphasias, whereas stimulation of the mid-temporal region and inferior fronto-occipital fasciculus produced naming errors without language specificity. These findings highlight both shared and distinct \u003cem\u003eloci\u003c/em\u003e for L1 and L2, advancing our understanding of bilingual brain organization.\u003c/p\u003e","manuscriptTitle":"Transient selective aphasia in highly proficient bilinguals triggered by electrical stimulation of the left superior temporal gyrus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-27 06:50:45","doi":"10.21203/rs.3.rs-5951755/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2025-03-30T19:10:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-27T08:01:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"312926987243125405573697141659034906399","date":"2025-03-27T07:27:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-26T22:21:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-26T11:12:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"Acta Neurochirurgica","date":"2025-03-26T09:54:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"acta-neurochirurgica","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anch","sideBox":"Learn more about [Acta Neurochirurgica](http://link.springer.com/journal/701)","snPcode":"701","submissionUrl":"https://submission.springernature.com/new-submission/701/3","title":"Acta Neurochirurgica","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"25e82f73-54c7-435a-abdd-dad00672e7e4","owner":[],"postedDate":"March 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-04-07T16:05:24+00:00","versionOfRecord":{"articleIdentity":"rs-5951755","link":"https://doi.org/10.1007/s00701-025-06508-5","journal":{"identity":"acta-neurochirurgica","isVorOnly":false,"title":"Acta Neurochirurgica"},"publishedOn":"2025-04-05 15:57:57","publishedOnDateReadable":"April 5th, 2025"},"versionCreatedAt":"2025-03-27 06:50:45","video":"","vorDoi":"10.1007/s00701-025-06508-5","vorDoiUrl":"https://doi.org/10.1007/s00701-025-06508-5","workflowStages":[]},"version":"v1","identity":"rs-5951755","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5951755","identity":"rs-5951755","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}