Repeated awake surgery and quality of life in patients with diffuse glioma: a systematic review and meta-analysis.

Diffuse gliomas significantly affect patients' daily lives. Because of the high risk of recurrence and anaplasic transformation, repeated surgery can be proposed in awake condition to prolongs overall survival by limiting and reducing residual tumour volume. However, oncological interest alone is no longer sufficient due to the consequent increase in median survival, and quality of life is becoming an important issue in clinical decision-making. This systematic review focuses on the effects of repeated surgery in awake condition on the quality of life of adults with diffuse glioma through three parameters: return to work, presence of postoperative neurocognitive disorders, and occurrence of epileptic seizures. A systematic review of the last 20 years was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards. Summarized data from selected studies were processed quantitatively, using a meta-analysis process, with the Review Manager 5.4 software. Five databases (PubMed, Web of Science, Science Direct, Dimensions, and Embase) were used. Fifteen articles were selected for qualitative analysis and 11 for meta-analysis. One hundred and fifty-one patients (85%) returned to an active socio-professional life after repeated surgery, and 78 (41%) presented neurocognitive disorders in the immediate postoperative period, only 3% (n = 4) of them suffering from permanent disorders. One hundred and forty-nine (78%) participants were free of epileptic seizure after repeated surgery. This systematic review of the literature highlights the benefit of repeated surgery on the quality of life of patients with adult diffuse glioma.

Moderate-to-severe obstructive sleep apnea syndrome is associated with altered tongue motion during wakefulness.

PURPOSE: Impairment of genioglossus control is a frequent "non-anatomical" cause of obstructive sleep apnea syndrome (OSAS) in non- or mildly obese patients. Although wake-related compensatory mechanisms prevent the occurrence of obstructive events, the genioglossus control is often impaired during wakefulness. We hypothesized that the lingual motion would be altered during wakefulness in this population in patients with moderate-to-severe OSAS. METHODS: We included non- or mildly obese participants with suspected OSAS. They underwent a Bucco-Linguo-Facial Motor Skills assessment using the MBLF ("Motricité Bucco-Linguo-Faciale"), which includes an evaluation of 13 movements of the tongue. This was followed by a night-attended polysomnography. We compared patients with moderate-to-severe OSAS (apnea-hypopnea index (AHI) ≥ 15/h; n = 15) to patients without or with mild OSAS (AHI < 15/h; n = 24). RESULTS: MBLF total and "tongue" sub-scores were lower in patients with moderate-to-severe OSAS: total z-score - 0.78 [- 1.31; 0.103] versus 0.20 [- 0.26; 0.31], p = 0.0011; "tongue" z-sub-score (- 0.63 [- 1.83; 0.41] versus 0.35 [0.26; 0.48], p = 0.014). There was a significant age-adjusted correlation between the "tongue" sub-score and AHI. The logistic regression model for the prediction of moderate-to-severe OSAS gave area under the curve ratio of 88.2% for MBLF score plus age. CONCLUSIONS: Myofunctional activity of the tongue is impaired during wakefulness in non- or mildly obese patients with moderate-to-severe OSAS. This study supports the lingual myofunctional assessment using the MBLF in screening of moderate-to-severe OSAS. This simple tool could help clinicians to select patients with suspected moderate-to-severe OSAS for polysomnography.

Outcomes and prognostic factors of facial nerve repair: a retrospective comparative study of 31 patients and literature review.

PURPOSE: To evaluate functional results of facial nerve repair by direct nerve suture or grafting, compare results between a traumatic and a tumoral group and identify prognostic factors. METHODS: A retrospective monocentric cohort study was studied in a university ENT department. Thirty-one patients who benefited from facial nerve suture or grafting, with at least 12 months postoperative follow-up were included. Patients were divided into two groups according to the lesion type: traumatic (accident of the public road or iatrogenic) and tumoral. Preoperative data studied were sex, side, etiology documented by CT and/or MRI, facial palsy duration and grade according to House Brackmann grading system. Intraoperative data included: surgeon, age of patient, surgical technique, graft type, use of biological glue, facial nerve derivation, lesioned site. Postoperative data included: histological diagnosis, radiotherapy history, time to onset of the first signs of reinnervation, follow-up duration, and final facial function. RESULTS: Success rate, including grade III and IV, was 68% in the whole cohort, 79% in the traumatic group and 59% in the tumoral group. Patients presenting with facial palsy evolving less than 6 months had better recovery results than those evolving longer than 6 months (p = 0.02). No other prognostic factors were identified. CONCLUSIONS: The best outcome that can be achieved by suture or grafting of the facial nerve in traumatic or tumoral lesions is a grade III. Preoperative facial palsy duration is a prognostic factor and must be considered when establishing an operative indication.

Oro-facial motor assessment: validation of the MBLF protocol in facial palsy.

BACKGROUND: Oro-facial myofunctional praxis assesses the muscular coordination and the degree of motor impairment of the lingual, mandibular and facial muscles necessary for articulation, mimicry and swallowing. PURPOSE: The objective of this study was to create and validate the MBLF protocol, a French oro-facial myofunctional assessment in order to quantify patient's impairment and to specify the motor and functional deficit for an adapted management. METHODS: The MBLF was validated against the Sunnybrook Facial Grading System (criterion validity). The construct validity was tested by comparing healthy subjects (n = 102) from patients with facial palsy (n = 60). Internal and external consistency of face symmetry were reported. Normative data was provided. RESULTS: There was a statistically significant correlation between the MBLF protocol and the Sunnybrook Facial Grading System [F(59) = 310.51, p < 0.001, R2 = 0.843]. Significant differences were observed in Student's t test between healthy volunteers and patients with facial palsy [t(74.13) = 14,704, p < 0.001, r = 0.863]. A significant effect of the severity grades of facial palsy on the MBLF_TOTAL scores was found [F(158) = 268.469, p < 0.001]. The more severe the facial palsy, the lower the motor scores were. CONCLUSION: This MBLF French validation provides a baseline for comparing and quantifying the performance of subjects. The MBLF protocol is valid for assessing facial symmetry in peripheral facial palsy. A prospective study is needed to validate its role in dynamic evaluation of facial palsy.

Impact of inspiratory threshold loading on brain activity and cognitive performances in healthy humans.

In healthy humans, inspiratory threshold loading deteriorates cognitive performances. This can result from motor-cognitive interference (activation of motor respiratory-related cortical networks vs. executive resources allocation), sensory-cognitive interference (dyspnea vs. shift in attentional focus), or both. We hypothesized that inspiratory loading would concomitantly induce dyspnea, activate motor respiratory-related cortical networks, and deteriorate cognitive performance. We reasoned that a concomitant activation of cortical networks and cognitive deterioration would be compatible with motor-cognitive interference, particularly in case of a predominant alteration of executive cognitive performances. Symmetrically, we reasoned that a predominant alteration of attention-depending performances would suggest sensory-cognitive interference. Twenty-five volunteers (12 men; 19.5-51.5 yr) performed the Paced Auditory Serial Addition Test (PASAT-A and B; calculation capacity, working memory, attention), the Trail Making Test (TMT-A, visuospatial exploration capacity; TMT-B, visuospatial exploration capacity, and attention), and the Corsi block-tapping test (visuospatial memory, short-term, and working memory) during unloaded breathing and inspiratory threshold loading in random order. Loading consistently induced dyspnea and respiratory-related brain activation. It was associated with deteriorations in PASAT-A [52 [45.5;55.5]; (median [interquartile range]) to 48 [41;54.5], P = 0.01], PASAT-B (55 [47.5;58] to 51 [44.5;57.5], P = 0.01), and TMT-B (44 s [36;54.5] to 53 s [42;64], P = 0.01), but did not affect TMT-A and Corsi. The concomitance of cortical activation and cognitive performance deterioration is compatible with competition for cortical resources (motor-cognitive interference), whereas the profile of cognitive impairment (PASAT and TMT-B but not TMT-A and Corsi) is compatible with a contribution of attentional distraction (sensory-cognitive interference). Both mechanisms are therefore likely at play.NEW & NOTEWORTHY To our knowledge, this is the first study exploring the interferences between inspiratory loading and cognition in healthy subjects with the concomitant use of neuropsychological tests and electroencephalographic recordings. Inspiratory loading was associated with dyspnea, respiratory-related changes in brain activation, and a pattern of deterioration of neuropsychological tests suggestive of attentional disruption. Inspiratory loading is therefore likely to impact cognitive performances through both motor-cognitive interference (engagement of cortical networks) and sensory-cognitive interference (dyspnea-related shift in attentional focus).

Is the human left middle longitudinal fascicle essential for language? A brain electrostimulation study.

Human brain pathways required for language processing are poorly known. A new white matter tract in humans, the middle longitudinal fascicle, has recently been anatomically determined by diffusion tensor imaging and suggested to be essential for language. Our aim is to determine the importance of the middle longitudinal fascicle for language processing. This study is based on 8 patients with glioma resection at least involving the superior temporal gyrus of the left dominant hemisphere. Language is systematically examined pre- and postoperatively at 3 months. Intraoperative electrostimulation is used to map cortical and subcortical structures as functional boundaries of the glioma resection, including those essential for language processing. The resections are extensive (on average 62 ml, ranging from 21 to 111 ml) and include a large part of the middle longitudinal fascicle in all patients. Intraoperatively, no interference with picture naming is observed by electrostimulation of the middle longitudinal fascicle, while in all patients the inferior fronto-occipital fascicle is identified by eliciting semantic paraphasia as functional boundary. Postoperatively, no new permanent language deficits are detected by systematic language examination. Therefore, we suggest that the middle longitudinal fascicle may participate but is not essential for language processing.

[Advantage of facial rehabilitation after facial palsy]. / Béncfices de la rééducation d'une paralysie faciale périphérique.

Visible and immediate trauma, facial palsy (FP) covers functional but also psychological damage and it is essential to evaluate before a comprehensive therapeutic care tailored. Few patients, however, are emerging with a prescription for rehabilitation after a consultation. Why? This rehabilitation is it ignored? Is it absolutely necessary? It is evident in the extension of medical care to minimize the effects. Yet the foundation of rehabilitation is sadly little known and often poorly enforced. In addition to its specificity, this therapy preceded by a report called "pretreatments offers a prognosis for recovery to patient" regardless of the origin and degree of involvement of the PF.

Speaking without Broca's area after tumor resection.

We present the case of a right-handed patient who received surgical treatment for a left frontal WHO grade II glioma invading the left inferior and middle frontal gyri, the head of the caudate nucleus, the anterior limb of the internal capsule and the anterior insula, in direct contact also with the anterior-superior part of the lentiform nucleus. The tumor resection was guided by direct electrical stimulation on brain areas, while the patient was awake. Adding a narrative production task to the neuropsychological assessment, we compared pre-, peri- and post-surgical language skills in order to analyze the effects of the tumor infiltration and the consequences of the left IFG resection, an area known to be involved in various language and cognitive processes. We showed that the tumor infiltration and its resection did not lead to the severe impairments predicted by the localization models assigning a significant role in language processing to the left frontal lobe, notably Broca's area. We showed that slow tumor evolution - the patient had been symptom-free for a long time - enabled compensatory mechanisms to process most language functions endangered by the tumor infiltration. However, a subtle fragility was observed in two language devices, i.e., reported speech and relative clauses, related to minor working memory deficits. This case study of a patient speaking without Broca's area illustrates the efficiency of brain plasticity, and shows the necessity to broaden pre-, peri-, post-surgery language and cognitive assessments.

Naming performance in two bilinguals with frontal vs. temporal glioma.

Two bilingual patients had World Health Organization Grade II Gliomas removed from a language area, one in the left mesiofronto-cingular region and one in the left postero-temporal region. They performed a picture naming task in their two languages before their surgery and afterwards. Both patients showed slowness in naming in their first language but different patterns of naming performance across their first and second language. Their patterns depended upon the site of their lesion and their language experience. These data, from brain-damaged, bilingual adult patients, contribute to the neuropsychological literature on brain organization and plasticity, and highlight the importance of assessing naming speed to obtain a better understanding of impairment and recovery mechanisms.

A discrete area within the left dorsolateral prefrontal cortex involved in visual-verbal incongruence judgment.

The role of the frontal lobe in cross-modal visual-auditory processing has been documented in experiments using incongruent/congruent paradigms. In this study, 4 patients with left frontal World Health Organization Grade II glioma were assessed during pre-, intra-, and postoperative sessions with picture-naming and verbal-visual task requiring judgment of congruence between pictures and words. During awake brain surgery, the naming and cross-modal tasks were coupled with electrical stimulation inactivating restricted specific regions. For all patients, focal brain stimulation in the dorsolateral prefrontal cortex elicited picture-word matching disturbances but no naming impairment, and the elicited errors exclusively appeared in incongruent and not congruent conditions. The dissociation observed between correct picture naming and disturbed cross-modal judgment shows that electrical stimulation of a discrete cortical area within the left dorsolateral prefrontal cortex can inhibit the simultaneous processing of visual-verbal information without disturbing larger networks involved in the naming process.

Functional outcome after language mapping for insular World Health Organization Grade II gliomas in the dominant hemisphere: experience with 24 patients.

OBJECT: Despite the report of recent experiences of insular surgery in the past decade, there has been no series specifically dedicated to studying functional outcome following resection of insular WHO Grade II gliomas involving the dominant hemisphere, in patients with no or only mild preoperative language deficit. In this article, the authors analyze the contribution of awake mapping for preservation of brain function, especially language, in a homogeneous series of 24 patients who underwent surgery for insular Grade II gliomas within the dominant insular lobe. METHODS: Twenty-four patients underwent surgery for an insular Grade II glioma involving the dominant hemisphere (22 left, 2 right), revealed by seizures in all but 1 case. The preoperative neurological examination result was normal in 17 patients (71%), whereas 7 patients presented with language disorders detected using an accurate language assessment performed by a speech therapist. All surgeries were performed on awake patients utilizing intra-operative language mapping involving cortical and subcortical stimulation. RESULTS: There were no intrasurgical complications or postsurgical sensorimotor deficits. Despite an immediate postoperative language worsening in 12 cases (50%), all patients recovered to a normal status within 3 months, and 6 cases even improved in comparison with their preoperative examination results. The 24 patients returned to normal social and professional lives. Moreover, the surgery had a favorable impact on epilepsy in all but 4 cases (83%). On control MR imaging, 62.5% of resections were total or subtotal. Three patients underwent a second or third awake surgery, with no additional deficit. All but 2 patients (92%) are alive after a mean follow-up of 3 years (range 3-133 months). CONCLUSIONS: Although insular surgery was long believed to be too risky, the present results show that the rate of permanent deficit, especially dysphasia, following resection of Grade II gliomas involving the dominant insula has been dramatically reduced (none in this patient series), thanks to the systematic use of intraoperative awake mapping, even in cases of repeated operations. Furthermore, patient quality of life may be improved due to a decrease of epilepsy after surgery. Thus, the authors suggest systematically considering resection when an insular Grade II glioma is diagnosed after seizures in a patient with no or mild deficit, even a glioma invading the dominant hemisphere.

Re-operation is a safe and effective therapeutic strategy in recurrent WHO grade II gliomas within eloquent areas.

BACKGROUND: To analyze the functional and oncological results after re-operation for recurrent WHO grade II Glioma located in eloquent regions. METHOD: We reviewed a consecutive series of 19 patients with GIIG within functional areas who underwent two operations separated by at least 1 year. Intraoperative electrical stimulation mapping was used in all operations for recurrence and in 14 of the initial procedures. A specific rehabilitation was provided. FINDINGS: At the first operation, we performed 14 subtotal and 5 partial resections. Eighteen patients returned to a normal socio-professional life. Nine patients received adjuvant treatment. At the second operation, we performed 1 total, 13 subtotal and 5 partial resections. Three patients with a preoperative neurological deficit improved, 13 remained unchanged, and 3 slight new deficits appeared. In 14 of the 17 patients with preoperative chronic epilepsy, the seizures were reduced or disappeared. Sixteen patients returned to a normal socio-professional life. Pathohistological examination showed that 11 tumours had progressed to high-grade glioma. The median time between the two operations was 4.1 years (range 1 to 7.8 years) and the median follow-up from initial diagnosis was 6.6 years (range 2.3 to 14.3 years). No deaths occurred during the follow-up period. CONCLUSIONS: Repeat operations guided by intra-operative electrical stimulation is an efficacious treatment for recurrent grade II glioma in an eloquent area.

Oral mobility reflects rate of progression in advanced Friedreich's ataxia.

Our objective was to identify a sensitive marker of disease progression in Friedreich's ataxia. We prospectively evaluated speech, voice, and oromotor function in 40 patients at two timepoints. The mean disease duration was 20.8 ± 9.8 years and mean SARA score 23.7 ± 8.6 at baseline. Oral motor mobility, assessed by a combination of movements of the face, eyes, cheeks, lips, and tongue, decreased significantly after 1 year (P < 0.0001). The standardized response mean over 12 months was considered as large for oral mobility (1.26) but small for SARA (0.12). Oral mobility could therefore be a sensitive marker in therapeutic trials.

Cortico-subcortical organization of language networks in the right hemisphere: an electrostimulation study in left-handers.

We have studied the configuration of the cortico-subcortical language networks within the right hemisphere (RH) in nine left-handers, being operated on while awake for a cerebral glioma. Intraoperatively, language was mapped using cortico-subcortical electrostimulation, to avoid permanent deficit. In frontal regions, cortical stimulation elicited articulatory disorders (ventral premotor cortex), anomia (dorsal premotor cortex), speech arrest (pars opercularis), and semantic paraphasia (dorsolateral prefrontal cortex). Insular stimulation generated dysarthria, parietal stimulation phonemic paraphasias, and temporal stimulation semantic paraphasias. Subcortically, the superior longitudinal fasciculus (inducing phonological disturbances when stimulated), inferior occipito-frontal fasciculus (eliciting semantic disturbances during stimulation), subcallosal fasciculus (generating control disturbances when stimulated), and common final pathway (inducing articulatory disorders during stimulation) were identified. These cortical and subcortical structures were preserved, avoiding permanent aphasia, despite a transient immediate postoperative language worsening. Both intraoperative results and postsurgical transitory dysphasia support the major role of the RH in language in left-handers, and provide new insights into the anatomo-functional cortico-subcortical organization of the language networks in the RH-suggesting a "mirror" configuration in comparison to the left hemisphere.

Long-term brain plasticity allowing a multistage surgical approach to World Health Organization Grade II gliomas in eloquent areas.

Although the goal of surgery for World Health Organization Grade II gliomas is maximal extent of resection, complete tumor removal is not always possible when the glioma involves eloquent areas. The authors propose a multistage surgical approach to highly crucial areas that are classically considered inoperable, enabling optimization of the extent of resection while avoiding permanent cognitive deficits due to induced functional reshaping in the interim between the 2 consecutive operations. To demonstrate such plasticity, the authors used a combination of sequential functional MR imaging and intraoperative electrical stimulation mapping before and during surgeries spaced by several years in 2 patients who each underwent 2 separate resections of Grade II gliomas located in the left dominant premotor area. During several years of follow-up after the first procedure, both patients had unremarkable examination results and normal socioprofessional lives. There was no malignant transformation. Based on their experience with these cases, the authors suggest that in cases of incomplete glioma removal, a second operation before anaplasia should be considered, made possible by brain reorganization after the first operation.

Does the left inferior longitudinal fasciculus play a role in language? A brain stimulation study.

Although advances in diffusion tensor imaging have enabled us to better study the anatomy of the inferior longitudinal fasciculus (ILF), its function remains poorly understood. Recently, it was suggested that the subcortical network subserving the language semantics could be constituted, in parallel with the inferior occipitofrontal fasciculus, by the left ILF, joining the posterior occipitotemporal regions to the temporal pole, then relayed by the uncinate fasciculus connecting the anterior temporal pole to the frontobasal areas. Nevertheless, this hypothesis was solely based on neurofunctional imaging, allowing a cortical mapping but with no anatomofunctional information regarding the white matter. Here, we report a series of 12 patients operated on under local anaesthesia for a cerebral low-grade glioma located within the left temporal lobe. Before and during resection, we used the method of intraoperative direct electrostimulation, enabling us to perform accurate and reliable anatomofunctional correlations both at cortical and subcortical levels. In order to map the ILF. Using postoperative MRI, we correlated these functional findings with the anatomical locations of the sites where language disturbances were elicited by stimulations, both at cortical and subcortical levels. Our goal was to study the potential existence of parallel and distributed language networks crossing the left dominant temporal lobe, subserved by distinct subcortical pathways--namely the inferior occipitofrontal fasciculus and the ILF. Intraoperative stimulation of the anterior and middle temporal cortex elicited anomia in four patients. At the subcortical level, semantic paraphasia were induced in seven patients during stimulation of the inferior occipitofrontal fasciculus, and phonological paraphasia was generated in seven patients by stimulating the arcuate fasciculus. Interestingly, subcortical stimulation never elicited any language disturbances when performed at the level of the ILF. In addition, following a transient postoperative language deficit, all patients recovered, despite the resection of at least one part of the ILF, as confirmed by control MRI. On the basis of these results, we suggest that the "semantic ventral stream" could be constituted by at least two parallel pathways within the left dominant temporal lobe: (i) a direct pathway, the inferior occipitofrontal fasciculus, that connects the posterior temporal areas and the orbitofrontal region, crucial for language semantic processing, since it elicits semantic paraphasia when stimulated; (ii) and also possibly an indirect pathway subserved by the ILF, not indispensable for language, since it can be compensated both during stimulation and after resection.

Involuntary language switching in two bilingual patients during the Wada test and intraoperative electrocortical stimulation.

We present two bilingual patients without language disorders in whom involuntary language switching was induced. The first patient switched from Dutch to English during a left-sided amobarbital (Wada) test. Functional magnetic resonance imaging yielded a predominantly left-sided language distribution similar for both languages. The second patient switched from French to Chinese during intraoperative electrocortical stimulation of the left inferior frontal gyrus. We conclude that the observed language switching in both cases was not likely the result of a selective inhibition of one language, but the result of a temporary disruption of brain areas that are involved in language switching. These data complement the few lesion studies on (involuntary or unintentional) language switching, and add to the functional neuroimaging studies of switching, monitoring, and controlling the language in use.

Smile Reanimation after Unilateral Facial Palsy by Lengthening Temporalis Myoplasty: Objective and Subjective Evaluation on 25 Cases.

BACKGROUND: Comparison of functional results of lengthening temporalis myoplasty relies in current practice on subjective scales. The goal of this study was to define a simple, reproducible, objective scale validated through a comparison with a subjective scale for smile symmetrization results after temporal muscle myoplasty. METHODS: A retrospective study was conducted on 25 patients having a unilateral facial palsy and rehabilitated with lengthening temporalis myoplasty. Evaluation consisted of objective measures: smile horizontal symmetry between left and right sides, vertical symmetry, and smile width on healthy and paretic sides on preoperative and postoperative photographs. Subjective scales were also used (i.e., a numeric scale and the Terzis and Noah scale) by a jury (four professionals and four nonprofessionals) and the patient himself or herself. Each evaluation was performed in three conditions: at rest, at intermediary smile, and at maximum smile. RESULTS: Comparison of objective measures on the impaired side showed a postoperative improvement in the three conditions evaluation. Reproducibility of the numeric scale was weak for evaluation at rest and fair for maximum smile evaluation (intraclass correlation coefficient of 0.57). The Terzis and Noah scale was not reproducible from one observer to another. At maximum smile, a correlation between smile symmetry in the vertical plane, smile symmetry in the horizontal plane, and professional evaluation with the numeric scale on the one hand and global patient satisfaction on the other hand was observed. CONCLUSION: Postoperative smile horizontal symmetry between left and right sides, and smile vertical symmetry, are good indicators with which to assess postoperative results of facial palsy rehabilitation.

Superior longitudinal fasciculus subserves vestibular network in humans.

Vestibular function is known to be represented in a large-scale network within the brain. Although much is known about the topography of this cortical network, the subcortical anatomo-functional connectivity has received less attention. We present three patients operated on while conscious for cerebral low-grade gliomas, in which we elicited vestibular symptoms during subcortical stimulation. Anatomo-functional correlations between postoperative imaging and intraoperative findings suggest the involvement of the superior longitudinal fasciculus in the spreading of the vestibular symptoms. We argue that this fasciculus plays a major role in the functional connectivity of the areas involved in the complex multimodal network that controls vestibular function.

New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical electrostimulations.

Despite a better understanding of the organization of the cortical network underlying the semantic system, very few data are currently available regarding its anatomo-functional connectivity. Here, we report on a series of 17 patients operated on under local anaesthesia for a cerebral low-grade glioma located within the dominant hemisphere. Prior to and during resection, intraoperative electrical stimulation was used to map sensorimotor and language structures so that permanent neurological deficits could be avoided. In a number of cases, cortical and subcortical stimulation caused semantic paraphasias. Using postoperative MRI, we correlated these functional findings with the anatomical locations of the sites where semantic errors were elicited by stimulation, especially at the subcortical level, with the aim of studying the connectivity underlying the semantic system. In temporal gliomas, cortical sites involved in semantic processing were found around the posterior part of the superior temporal sulcus, with subcortical pathways reproducibly located under the depth of this sulcus. In insular gliomas, although stimulation elicited no semantic disturbances at the cortical level, such semantic paraphasias were generated at the level of the anterior floor of the external capsule. In frontal tumours, cortical regions implicated in semantics were detected in the lateral orbitofrontal region and dorsolateral prefrontal cortex, with subcortical fibres located under the inferior frontal sulcus. All these eloquent structures were systematically preserved, thereby avoiding permanent postoperative deficits. Our results provide arguments in favour of the existence of a main ventral subcortical pathway underlying the semantic system, within the dominant hemisphere, joining the two essential cortical epicentres of this network: the posterior and superior temporal areas, and the orbitofrontal and dorsolateral prefontal regions. Such a ventral stream might anatomically partly correspond to the inferior fronto-occipital fasciculus.