Deficits in naming pictures of objects are associated with glioma infiltration of the inferior longitudinal fasciculus: A study with diffusion MRI tractography, volumetric MRI, and neuropsychology.

It has been suggested that the inferior longitudinal fasciculus (ILF) may play an important role in several aspects of language processing such as visual object recognition, visual memory, lexical retrieval, reading, and specifically, in naming visual stimuli. In particular, the ILF appears to convey visual information from the occipital lobe to the anterior temporal lobe (ATL). However, direct evidence proving the essential role of the ILF in language and semantics remains limited and controversial. The first aim of this study was to prove that patients with a brain glioma damaging the left ILF would be selectively impaired in picture naming of objects; the second aim was to prove that patients with glioma infiltrating the ATL would not be impaired due to functional reorganization of the lexical retrieval network elicited by the tumor. We evaluated 48 right-handed patients with neuropsychological testing and magnetic resonance imaging (MRI) before and after surgery for resection of a glioma infiltrating aspects of the left temporal, occipital, and/or parietal lobes; diffusion tensor imaging (DTI) was acquired preoperatively in all patients. Damage to the ILF, inferior frontal occipital fasciculus (IFOF), uncinate fasciculus (UF), arcuate fasciculus (AF), and associated cortical regions was assessed by means of preoperative tractography and pre-/pos-toperative MRI volumetry. The association of fascicles damage with patients' performance in picture naming and three additional cognitive tasks, namely, verbal fluency (two verbal non-visual tasks) and the Trail Making Test (a visual attentional task), was evaluated. Nine patients were impaired in the naming test before surgery. ILF damage was demonstrated with tractography in six (67%) of these patients. The odds of having an ILF damage was 6.35 (95% CI: 1.27-34.92) times higher among patients with naming deficit than among those without it. The ILF was the only fascicle to be significantly associated with naming deficit when all the fascicles were considered together, achieving an adjusted odds ratio of 15.73 (95% CI: 2.30-178.16, p = .010). Tumor infiltration of temporal and occipital cortices did not contribute to increase the odd of having a naming deficit. ILF damage was found to be selectively associated with picture naming deficit and not with lexical retrieval assessed by means of verbal fluency. Early after surgery, 29 patients were impaired in naming objects. The association of naming deficit with percentage of ILF resection (assessed by 3D-MRI) was confirmed (beta = -56.78 ± 20.34, p = .008) through a robust multiple linear regression model; no significant association was found with damage of IFOF, UF or AF. Crucially, postoperative neuropsychological evaluation showed that naming scores of patients with tumor infiltration of the anterior temporal cortex were not significantly associated with the percentage of ILF damage (rho = .180, p > .999), while such association was significant in patients without ATL infiltration (rho = -.556, p = .004). The ILF is selectively involved in picture naming of objects; however, the naming deficits are less severe in patients with glioma infiltration of the ATL probably due to release of an alternative route that may involve the posterior segment of the AF. The left ILF, connecting the extrastriatal visual cortex to the anterior region of the temporal lobe, is crucial for lexical retrieval on visual stimulus, such as in picture naming. However, when the ATL is also damaged, an alternative route is released and the performance improves.

Patient-reported outcome and cognitive measures to be used in vascular and brain tumor surgery: proposal for a minimum set.

BACKGROUND: The standardization of outcome measures is needed for comparing studies and using common measures in clinical practice. We aimed to identify cognitive and patient-reported outcomes and timing of assessment for glioma, meningioma, and vascular surgery. METHOD: A consensus study was conducted. Participants selected cognitive and patient-reported measures among a list of instruments identified through a literature search. RESULTS: Seventeen cognitive tests for the glioma and meningioma's evaluation, 8 for the vascular diseases, and one questionnaire on quality of life and one on emotional distress were identified. The timing of outcome assessment selected was before surgery, at discharge, and after 3 and 12 months for glioma; before surgery and after 3 months for meningioma; before surgery, at discharge, and after 6 months for vascular diseases. CONCLUSION: The identification of common outcome measures is the first step toward a shared data collection improving the quality and comparability of future studies.

A new test of action verb naming: normative data from 290 Italian adults.

INTRODUCTION: Verbs and nouns can be selectively impaired, suggesting that they are processed, at least in part, by distinct neural structures. While several tests of object naming are available, tasks involving action verb naming with normative data are lacking. We report the construction and standardization of a new test for the assessment of picture naming of actions. MATERIAL AND METHODS: The test includes 50 stimuli, strictly controlled for several confounding variables. Normative data on 290 Italian subjects pooled across homogenous subgroups for age, sex, and education are reported. RESULTS: Multiple regression analyses revealed that age and education significantly correlated with the subject's score. In particular, increasing age negatively affected performance, while the performance increased with a higher education. CONCLUSIONS: In the clinical practice, the availability of equivalent scores will help the comparison with performance in the picture naming of objects. This test allows investigating action naming deficits in aphasic patients, in Parkinson's disease patients and in further neurodegenerative disorders, in which a specific impairment of action verbs is expected, filling a gap in the clinical neuropsychological assessment.

Mapping the brain network of the phonological loop.

The cortical and subcortical neural correlates underlying item and order information in verbal short-term memory (STM) were investigated by means of digit span in 29 patients with direct electrical stimulation during awake surgery for removal of a neoplastic lesion. Stimulation of left Broca's area interfered with span, producing significantly more item than order errors, as compared to the stimulation of the supramarginal/angular gyrus, which also interfered with span but, conversely, produced more order than item errors. Similarly, stimulation of the third segment of the left superior longitudinal fasciculus (SLF-III), also known as anterior segment of the arcuate fascicle (AF), produced more order than item errors. Therefore, we obtained two crucial results: first, we were able to distinguish between content and order information storage. Second, we demonstrated that the SLF-III is involved in transferring order information from Geschwind's area to Broca's area. In a few patients, we demonstrated that also order information of nonverbal material was disrupted by left supramarginal gyrus stimulation. Order information is thus likely stored in the supramarginal gyrus, possibly independently from the nature of the material. Hum Brain Mapp 38:3011-3024, 2017. © 2017 Wiley Periodicals, Inc.

The mirror neuron system and the strange case of Broca's area.

Mirror neurons, originally described in the monkey premotor area F5, are embedded in a frontoparietal network for action execution and observation. A similar Mirror Neuron System (MNS) exists in humans, including precentral gyrus, inferior parietal lobule, and superior temporal sulcus. Controversial is the inclusion of Broca's area, as homologous to F5, a relevant issue in light of the mirror hypothesis of language evolution, which postulates a key role of Broca's area in action/speech perception/production. We assess "mirror" properties of this area by combining neuroimaging and intraoperative neurophysiological techniques. Our results show that Broca's area is minimally involved in action observation and has no motor output on hand or phonoarticulatory muscles, challenging its inclusion in the MNS. The presence of these functions in premotor BA6 makes this area the likely homologue of F5 suggesting that the MNS may be involved in the representation of articulatory rather than semantic components of speech.

Cerebral correlates of visuospatial neglect: a direct cerebral stimulation study.

OBJECTIVE: To assess the role of the superior longitudinal fascicle, the inferior fronto-occipital fascicle, and the posterior parietal lobe in visuospatial attention in humans during awake brain surgery. EXPERIMENTAL DESIGN: Seven patients with hemispheric gliomas (six in the right hemisphere) entered the study. During surgery in asleep/awake anesthesia, guided by Diffusion Tensor Imaging Fiber Tractography, visuospatial neglect was assessed during direct electrical stimulation by computerized line bisection. PRINCIPAL OBSERVATIONS: A rightward deviation, indicating left visuospatial neglect, was induced in six of seven patients by stimulation of the parietofrontal connections, in a location consistent with the trajectory of the second branch of the superior longitudinal fascicle. Stimulation of the medial and dorsal white matter of the superior parietal lobule (corresponding to the first branch of the superior longitudinal fascicle), of the ventral and lateral white matter of the supramarginal gyrus (corresponding to the third branch of the superior longitudinal fascicle), and of the inferior occipitofrontal fasciculus, was largely ineffective. Stimulation of the superior parietal lobule (Brodmann's area 7) caused a marked rightward deviation in all of the six assessed patients, while stimulation of Brodmann's areas 5 and 19 was ineffective. CONCLUSIONS: The parietofrontal connections of the dorso-lateral fibers of the superior longitudinal fascicle (i.e., the second branch of the fascicle), and the posterior superior parietal lobe (Brodmann's area 7) are involved in the orientation of spatial attention. Spatial neglect should be assessed systematically during awake brain surgery, particularly when the right parietal lobe may be involved by the neurosurgical procedure.

A new standardization of semantic verbal fluency test.

Semantic verbal fluency test is frequently used in clinical practice to assess lexical retrieval and production in neurological and psychiatric diseases. Semantic category is a crucial variable to consider in patients with language disorders. Norms for this task were collected from a population of 290 Italian healthy participants with age ranging from 18 to 98 years. The aim was to provide normative data both for the global score and for each semantic category (animals, fruits, brands of cars). Multiple regression analysis revealed that age and education significantly correlated with the global score and with single semantic categories. In particular, increasing age negatively affected performance, whereas the performance increased with a higher education. Statistically significant differences between men and women were found only for brands of cars. The availability of equivalent scores for the single semantic categories will prove useful in clinical practice since it allows the comparison of single semantic categories in patients with language disorders.

Measuring clinical outcomes in neuro-oncology. A battery to evaluate low-grade gliomas (LGG).

We describe how a neuropsychological evaluation in patients with brain tumors should be performed, specifically in the case of low-grade gliomas. Neuropsychological examination is crucial before starting any treatment as well as during the follow-up, since it can improve neurosurgery techniques and reveal potential cognitive effects of chemotherapy and radiotherapy, besides planning rehabilitation. We underline that sensitive and wide-ranging tests are required; specific tasks based on the lesion site should be added. Moreover, some tests can provide additional information about the evolution of the tumor. A careful, thorough examination improves quality of life.

Decision-making abilities in patients with frontal low-grade glioma.

Decisions in daily life are often quite complex, especially when one has to decide about his/her own health, as it is the case for patients with brain tumours. The integrity of the prefrontal cortex (and of the orbito-frontal in particular) is crucial in humans for practical decision-making. We investigated decision-making in 22 right-handed patients with a left frontal low-grade glioma, by means of a more complex, computerized version of the Iowa gambling task and we compared their performance with that of 26 neurologically-unimpaired subjects. After the experiment, we also administered a questionnaire to evaluate subjects' conscious comprehension level of the task and two self-report scales to verify potential effects of individual personality differences. Patients chose significantly less cards than controls from the advantageous deck, without modifying their behaviour over time, and this correlated with abstract reasoning abilities. In both groups, level of comprehension, significantly affected performance. An improvement was found post-surgery. In conclusion, the performance in the Gambling Task suggests that patients with left frontal low-grade gliomas can be impaired in decision-making, apparently requiring more time to understand the task: therefore, a particular attention and care should be taken to explain risks and consequences of his/her illness and treatment in order to obtain an informed decision from the patient.

What is the role of the uncinate fasciculus? Surgical removal and proper name retrieval.

The functional role of the uncinate fasciculus is still a matter of debate. We examined 44 patients submitted to awake surgery for removal of a left frontal or temporal glioma. In 18 patients, the removal included the uncinate fasciculus. We compared patients with or without removal on a series of neuropsychological tasks, performed at different time intervals: pre-surgery, in the first week after surgery and 3 months after surgery. Functional magnetic resonance and diffusion tensor imaging, fibre-tracking techniques were performed before surgery. At the last examination, patients with uncinate removal were significantly impaired in naming of famous faces and objects as compared with patients without removal. We further divided patients according to the site of the tumour (either frontal or temporal). At the follow-up, patients with a temporal glioma who underwent uncinate removal had the worst loss of performance in famous face naming. In addition, on the same task, the group with a frontal glioma that underwent resection of the frontal part of the uncinate performed significantly worse than the group with a frontal glioma but without uncinate removal. In conclusion, the resection of the uncinate fasciculus, in its frontal or temporal part, has long-lasting consequences for famous face naming. We suggest that this fibre tract is part of a circuitry involved in the retrieval of word form for proper names. Retrieval of conceptual knowledge was intact.

Re-irradiation for recurrent high grade glioma (HGG) patients: Results of a single arm prospective phase 2 study.

BACKGROUND AND PURPOSE: Standard of care for recurrent high grade glioma (HGG) is missing. Several treatment options have been investigated including re-irradiation (re-RT). Results are promising but provided by retrospective studies. We designed a single arm prospective phase II study aiming to evaluate efficacy, and toxicity of re-irradiation. MATERIALS AND METHODS: Adults patients with good performance status, HGG diagnosis reclassified according to the new 2021 fifth edition WHO CNS classification, an interval time (IT) from previous RT ≥ 6 months were included. Outcome was evaluated by MRI imaging at 1 month, and every 3 months thereafter. Toxicities were evaluated in terms of radionecrosis occurrence, and neurocognitive status. RESULTS: Ninety recurrent HGG patients were treated, 11 oligodendroglioma grade 3, 18 astrocytoma grade 3 and 4, and 61 glioblastoma grade 4. The median age was 54 years, and majority had KPS 90-100. The median IT between first-RT and re-RT was 24 months. Re-surgery has been performed in 56.6%, and chemotherapy in 53.3%. The median follow up time was 64 months; median overall survival (OS) time,1,2,3-year OS rates were 17 months (95%CI 14-19), 66.7%±4.9, 32.6%±5.0, and 22.2 ± 4.7. Prognostic factors impacting on survival were age (p = 0.0154), IT between first RT and re-RT (p = 0.0051), glioma grade (p = 0.0090), and IDH status (p = 0.0001). Radionecrosis grade 2-3 occurred in 9 (10%) patients; neurocognitive functions remained stable until disease progression. CONCLUSION: Re-RT proved to be a safe and feasible treatment option with low toxicity. Younger patients with grade 3 IDH mutated gliomas, and a longer IT had the better outcome. TRIAL REGISTRATION NUMBER: NCT02567539.

Connectivity constraints on cortical reorganization of neural circuits involved in object naming.

The brain's plasticity in response to sensory deprivation and other perturbations is well established. While the functional properties of the reorganized areas are under vigorous investigation, the factors that constrain cortical reorganization remain poorly understood. One factor constraining such reorganization may be long-distance subcortical connectivity between relevant cortical regions-reorganization attempts to preserve the functionality of subcortical connections. Here we provide human neurophysiological evidence for the role of the subcortical connections in shaping cortical reorganization of the networks involved in object naming following perturbation of normal function. We used direct electrical stimulation (DES) during surgical removal of gliomas to identify the sites that are involved in naming different categories of objects. The sites that were selectively inhibited in naming either living or non-living objects were displaced relative to those observed with other subject populations, possibly reflecting cortical reorganization due to slowly evolving brain damage. Subcortical DES applied to the white matter underlying these regions also led to category-specific naming deficits. The existence of these subcortical fiber pathways was confirmed using diffusion tensor tractography. These results constitute the first neurophysiological evidence for the critical role of subcortical pathways as part of the neural circuits that are involved in object naming; they also highlight the importance of subcortical connectivity in shaping cortical reorganization following perturbations of normal function.

Role of 11C Methionine Positron Emission Tomography (11CMETPET) for Surgery and Radiation Therapy Planning in Newly Diagnosed Glioblastoma Patients Enrolled into a Phase II Clinical Study.

(1) Background: We investigated the role of [11C]-methionine PET in a cohort of newly diagnosed glioblastoma multiforme (GBM) patients to evaluate whether it could modify the extent of surgical resection and improve radiation therapy volume delineation. (2) Methods: Newly diagnosed GBM patients, ages 18-70, with a Karnofsky performance scale (KPS) ≥ 70 with available MRI and [11C]-methionine PET were included. Patients were treated with different amounts of surgical resection followed by radio-chemotherapy. The role of [11C]-methionine PET in surgical and RT planning was analyzed. A threshold of SUVmax was searched. (3) Results: From August 2013 to April 2016, 93 patients were treated and included in this analysis. Residual tumor volume was detected in 63 cases on MRI and in 78 on [11C]-methionine PET, including 15 receiving gross total resection. The location of uptake was mainly observed in FLAIR abnormalities. [11C]-methionine uptake changed RT volume in 11% of patients. The presence of [11C]-methionine uptake in patients receiving GTR proved to influence survival (p = 0.029). The threshold of the SUVmax conditioning outcome was five. (4) Conclusions: [11C]-methionine PET allowed to detect areas at higher risk of recurrence located in FLAIR abnormalities in patients affected by GBM. A challenging issue is represented by integrating morphological and functional imaging to better define the extent of surgical resection to perform.

fMRI-Targeted High-Angular Resolution Diffusion MR Tractography to Identify Functional Language Tracts in Healthy Controls and Glioma Patients.

BACKGROUND: MR Tractography enables non-invasive preoperative depiction of language subcortical tracts, which is crucial for the presurgical work-up of brain tumors; however, it cannot evaluate the exact function of the fibers. PURPOSE: A systematic pipeline was developed to combine tractography reconstruction of language fiber bundles, based on anatomical landmarks (Anatomical-T), with language fMRI cortical activations. A fMRI-targeted Tractography (fMRI-T) was thus obtained, depicting the subsets of the anatomical tracts whose endpoints are located inside a fMRI activation. We hypothesized that fMRI-T could provide additional functional information regarding the subcortical structures, better reflecting the eloquent white matter structures identified intraoperatively. METHODS: Both Anatomical-T and fMRI-T of language fiber tracts were performed on 16 controls and preoperatively on 16 patients with left-hemisphere brain tumors, using a q-ball residual bootstrap algorithm based on High Angular Resolution Diffusion Imaging (HARDI) datasets (b = 3000 s/mm2; 60 directions); fMRI ROIs were obtained using picture naming, verbal fluency, and auditory verb generation tasks. In healthy controls, normalized MNI atlases of fMRI-T and Anatomical-T were obtained. In patients, the surgical resection of the tumor was pursued by identifying eloquent structures with intraoperative direct electrical stimulation mapping and extending surgery to the functional boundaries. Post-surgical MRI allowed to identify Anatomical-T and fMRI-T non-eloquent portions removed during the procedure. RESULTS: MNI Atlases showed that fMRI-T is a subset of Anatomical-T, and that different task-specific fMRI-T involve both shared subsets and task-specific subsets - e.g., verbal fluency fMRI-T strongly involves dorsal frontal tracts, consistently with the phonogical-articulatory features of this task. A quantitative analysis in patients revealed that Anatomical-T removed portions of AF-SLF and IFOF were significantly greater than verbal fluency fMRI-T ones, suggesting that fMRI-T is a more specific approach. In addition, qualitative analyses showed that fMRI-T AF-SLF and IFOF predict the exact functional limits of resection with increased specificity when compared to Anatomical-T counterparts, especially the superior frontal portion of IFOF, in a subcohort of patients. CONCLUSION: These results suggest that performing fMRI-T in addition to the 'classic' Anatomical-T may be useful in a preoperative setting to identify the 'high-risk subsets' that should be spared during the surgical procedure.

Intraoperative mapping and monitoring of brain functions for the resection of low-grade gliomas: technical considerations.

Low-grade gliomas ([LGGs] WHO Grade II) are slow-growing intrinsic cerebral lesions that diffusely infiltrate the brain parenchyma along white matter tracts and almost invariably show a progression toward malignancy. The treatment of these tumors forces the neurosurgeon to face uncommon difficulties and is still a subject of debate. At the authors' institution, resection is the first option in the treatment of LGGs. It requires the combined efforts of a multidisciplinary team of neurosurgeons, neuroradiologists, neuropsychologists, and neurophysiologists, who together contribute to the definition of the location, extension, and extent of functional involvement that a specific lesion has caused in a particular patient. In fact, each tumor induces specific modifications of the brain functional network, with high interindividual variability. This requires that each treatment plan is tailored to the characteristics of the tumor and of the patient. Consequently, surgery is performed according to functional and anatomical boundaries to achieve the maximal resection with maximal functional preservation. The identification of eloquent cerebral areas, which are involved in motor, language, memory, and visuospatial functions and have to be preserved during surgery, is performed through the intraoperative use of brain mapping techniques. The use of these techniques extends surgical indications and improves the extent of resection, while minimizing the postoperative morbidity and safeguarding the patient's quality of life. In this paper the authors present their paradigm for the surgical treatment of LGGs, focusing on the intraoperative neurophysiological monitoring protocol as well as on the brain mapping technique. They briefly discuss the results that have been obtained at their institution since 2005 as well as the main critical points they have encountered when using this approach.

The neural correlates of auditory-verbal short-term memory: a voxel-based lesion-symptom mapping study on 103 patients after glioma removal.

The relationship between verbal-auditory short-term memory (STM) and language is an open area of debate and contrasting hypotheses have been proposed, suggesting either that STM would strongly rely on language-related processes, or that it depends on a dedicated system related to language, but independent from it. In this study we examined 103 patients undergoing surgery for glioma resection in the left or right hemisphere, and we conducted a VLSM analysis on their behavioral performance on auditory-verbal STM, as well as on more general verbal and nonverbal tasks. The aim was to investigate whether the anatomical correlates of auditory-verbal STM were part of the language system or they were spatially segregated from it. VLSM results showed that digit span scores were linked to lesions in both the left supramarginal gyrus and superior-posterior temporal areas, as reported in the literature on patients with a selective deficit of auditory-verbal STM. Conversely, other verbal tasks involved areas only partly overlapping with those found for digit span, with repetition being affected by lesions in more anterior regions in the parietal, temporal, and frontal lobes, and word comprehension by lesions in a network including cortical and subcortical pathways in the temporal lobe. The present results, thus, show that auditory-verbal STM neural correlates are only partially overlapping with those supporting comprehension and production: while the left posterior-superior temporal cortex, involved in speech perception, takes part in both functions, the left supramarginal gyrus has a consistent and specific role only in STM, supporting the hypothesis of interacting but segregated networks.

Consequences of brain tumour resection on emotion recognition.

Emotion processing impairments are common in patients undergoing brain surgery for fronto-temporal tumour resection, with potential consequences on social interactions. However, evidence is controversial concerning side and site of lesions causing such deficits. This study investigates visual and auditory emotion recognition in brain tumour patients with the aim of clarifying which lesion sites are related to impairments in emotion processing from different modalities. Thirty-four patients were evaluated, before and after surgery, on facial expression and emotional prosody recognition; voxel-based lesion-symptom mapping (VLSM) analyses were performed on patients' post-surgery MRI images. Results showed that patients' performance decreased after surgery in both visual and auditory modalities, but, in general, recovered 3 months after surgery. In facial expression recognition, left brain-damaged patients showed greater post-surgery deterioration than right brain-damaged ones, whose performance specifically decreased for sadness and fear. VLSM analysis revealed two segregated areas in the left hemisphere accounting for post-surgery scores for happy (fronto-temporo-insular region) and surprised (middle frontal gyrus and inferior fronto-occipital fasciculus) facial expressions. Our findings demonstrate that surgical removal of tumours in the fronto-temporal region produces impairment in facial emotion recognition with an overall recovery at 3 months, suggesting a partially different representation of positive and negative emotions in the left and right hemispheres for visually - but not auditory - presented emotions; moreover, we show that deficits in specific expression recognition are associated with discrete lesion locations.

Object-action dissociation: A voxel-based lesion-symptom mapping study on 102 patients after glioma removal.

Data concerning the neural basis of noun and verb processing are inconsistent. Some authors assume that action-verb processing is based on frontal areas while nouns processing relies on temporal regions; others argue that the circuits processing verbs and nouns are closely interconnected in a predominantly left-lateralized fronto-temporal-parietal network; yet, other researchers consider that the primary motor cortex plays a crucial role in processing action verbs. In the present study, one hundred and two patients with a tumour either in the right or left hemisphere were submitted to picture naming of objects and actions before and after surgery. To test the effect of specific brain regions in object and action naming, patients' lesions were mapped and voxel-lesion-symptom mapping (VLSM) was computed. Behavioural results showed that left-brain damaged patients were significantly more impaired than right brain-damaged patients. The VLSM showed that these two grammatical classes are segregated in the left hemisphere. In particular, scores in naming of objects correlated with damage to the anterior temporal region, while scores in naming of actions correlated with lesions in the parietal areas and in the posterior temporal cortex. In addition, VLSM analyses carried out on non-linguistic tasks were not significant, confirming that the regions associated with deficits in object and action naming were not generally engaged in all cognitive tasks. Finally, the involvement of subcortical pathways was investigated and the inferior longitudinal fasciculus proved to play a role in object naming, while no specific bundle was identified for actions.

Preserving executive functions in nondominant frontal lobe glioma surgery: an intraoperative tool.

OBJECTIVE: The goal of surgery for gliomas is maximal tumor removal while preserving the patient's full functional integrity. At present during frontal tumor removal, this goal is mostly achieved, although the risk of impairing the executive functions (EFs), and thus the quality of life, remains significant. The authors investigated the accuracy of an intraoperative version of the Stroop task (iST), adapted for intraoperative mapping, to detect EF-related brain sites by evaluating the impact of the iST brain mapping on preserving functional integrity following a maximal tumor resection. METHODS: Forty-five patients with nondominant frontal gliomas underwent awake surgery; brain mapping was used to establish the functional boundaries for the resection. In 18 patients language, praxis, and motor functions, but not EFs (control group), were mapped intraoperatively at the cortical-subcortical level. In 27 patients, in addition to language, praxis, and motor functions, EFs were mapped with the iST at the cortical-subcortical level (Stroop group). In both groups the EF performance was evaluated preoperatively, at 7 days and 3 months after surgery. RESULTS: The iST was successfully administered in all patients. Consistent interferences, such as color-word inversion/latency, were obtained by stimulating precise white matter sites below the inferior and middle frontal gyri, anterior to the insula and over the putamen, and these were used to establish the posterior functional limit of the resection. Procedures implemented with iST dramatically reduced the EF deficits at 3 months. The EOR was similar in Stroop and control groups. CONCLUSIONS: Brain mapping with the iST allows identification and preservation of the frontal lobe structures involved in inhibition of automatic responses, reducing the incidence of postoperative EF deficits and enhancing the further posterior and inferior margin of tumor resection.