Multivariate mapping of low-resilient neurocognitive systems within and around low-grade gliomas.

Accumulating evidence suggests that the brain exhibits a remarkable capacity for functional compensation in response to neurological damage, a resilience potential that is deeply rooted in the malleable features of its underlying anatomofunctional architecture. This propensity is particularly exemplified by diffuse low-grade glioma, a subtype of primary brain tumour. However, functional plasticity is not boundless, and surgical resections directed at structures with limited neuroplasticity can lead to incapacitating impairments. Yet, maximizing diffuse low-grade glioma resections offers substantial oncological benefits, especially when the resection extends beyond the tumour margins (i.e. supra-tumour or supratotal resection). In this context, the primary objective of this study was to identify which cerebral structures were associated with less favourable cognitive outcomes after surgery, while accounting for intra-tumour and supra-tumour features of the surgical resections. To achieve this objective, we leveraged a unique cohort of 400 patients with diffuse low-grade glioma who underwent surgery with awake cognitive mapping. Patients benefitted from a neuropsychological assessment consisting of 18 subtests administered before and 3 months after surgery. We analysed changes in performance and applied topography-focused and disconnection-focused multivariate lesion-symptom mapping using support vector regressions, in an attempt to capture resected cortico-subcortical structures less amenable to full cognitive compensation. The observed changes in performance were of a limited magnitude, suggesting an overall recovery (13 of 18 tasks recovered fully despite a mean resection extent of 92.4%). Nevertheless, lesion-symptom mapping analyses revealed that a lack of recovery in picture naming was linked to damage in the left inferior temporal gyrus and inferior longitudinal fasciculus. Likewise, for semantic fluency abilities, an association was established with damage to the left precuneus/posterior cingulate. For phonological fluency abilities, the left dorsomedial frontal cortex and the frontal aslant tract were implicated. Moreover, difficulties in spatial exploration were associated with injury to the right dorsomedial prefrontal cortex and its underlying connectivity. An exploratory analysis suggested that supra-tumour resections were associated with a less pronounced recovery following specific resection patterns, such as supra-tumour resections of the left uncinate fasciculus (picture naming), the left corticostriatal tract and the anterior corpus callosum (phonological fluency), the hippocampus and parahippocampus (episodic memory) and the right frontal-mesial areas (visuospatial exploration). Collectively, these patterns of results shed new light on both low-resilient neural systems and the prediction of cognitive recovery following glioma surgery. Furthermore, they indicate that supra-tumour resections were only occasionally less well tolerated from a cognitive viewpoint. In doing so, they have deep implications for surgical planning and rehabilitation strategies.

Combining executive function training and anomia therapy in chronic post-stroke aphasia: A preliminary study of multidimensional effects.

PURPOSE: The influential relationship between executive functioning and aphasia rehabilitation outcomes has been addressed in a number of studies, but few have studied the effect of adding executive function training to linguistic therapies. The present study aimed to measure the effects of combining, within therapy sessions, executive function training and anomia therapy on naming and discourse abilities in people with chronic aphasia. METHOD: A single-case experimental design with multiple baselines across participants was used. Four persons with chronic post-stroke aphasia received 12 sessions of a tailored treatment combining executive function training and semantic feature analysis (SFA) therapy. Naming accuracy of treated items was examined over the course of the treatment while control naming scores of untreated items and discourse measures were collected pre-treatment, immediately post-treatment, and 4 weeks post-treatment, in order to investigate the multidimensional effects of the treatment and their maintenance. RESULT: Naming skills improved in all participants for treated and untreated items, were maintained over time, and were accompanied by improved discourse abilities. Visual and statistical analyses showed a significant treatment effect for naming skills in three out of the four participants. CONCLUSION: A combination of executive function training and SFA treatment in people with chronic aphasia may improve both naming skills and discourse efficiency. Further studies are needed to substantiate these promising preliminary results.

Is intraoperative mapping of music performance mandatory to preserve skills in professional musicians? Awake surgery for lower-grade glioma conducted from a meta-networking perspective.

OBJECTIVE: In surgery for lower-grade glioma (LGG) in professional musicians, for whom preserving music ability is essential, a critical question has emerged, namely, is it mandatory to include music performance during awake mapping, as proposed in several reports? In fact, music ability is subserved by a mosaic of interactive cognitive and emotional processes that rest on several networks. Therefore, from a meta-network perspective, the authors investigated whether an integrated multimodal monitoring of these cognitive and emotional functions during stimulation mapping could be efficient in maintaining musical skill. Indeed, it could be difficult for a patient to play a musical instrument in the surgical setting in addition to performing other tasks, such as movement and language. METHODS: An awake mapping-guided resection for LGG without intraoperative music performance was performed in 3 professional musicians. Intraoperative tests were tailored to each patient depending on the critical corticosubcortical circuits surrounding the tumor, including not only sensorimotor or language skills but also higher-order functions with a constant multitasking during the resection. RESULTS: Although music skills were not mapped during surgery, all patients resumed their professional activities, preserving the ability to play music and to perform concerts, to teach and to compose music, or to start learning a new instrument. CONCLUSIONS: A connectome-based resection without intraoperative music performance seems effective in achieving maximal glioma removal while preserving crucial networks subserving musical skills, creativity, and music learning. Neurosurgery should evolve toward a meta-networking approach to better understand higher-order functions mediating complex behavior, such as being a professional musician.

Disruption of the left anterior ventrolateral temporal cortex along with the inferior longitudinal fasciculus impairs the ability to retrieve famous face names: Evidence from three longitudinal case studies.

The cortical distribution of the proper name (PN) retrieval network has been widely studied contrary to its connectional anatomy. Here, we report the case of three patients with a low-grade glioma damaging the mid-to-anterior part of the left temporal lobe. A longitudinal behavioural assessment showed that the surgery caused a long-lasting decline in PN retrieval performances in all patients. Furthermore, a detailed analysis of surgery-related structural disconnections revealed that interruption of the inferior longitudinal fasciculus was the unique common denominator.

The central role of the left inferior longitudinal fasciculus in the face-name retrieval network.

Unsuccessful retrieval of proper names (PNs) is commonly observed in patients suffering from neurological conditions such as stroke or epilepsy. While a large body of works has suggested that PN retrieval relies on a cortical network centered on the left anterior temporal lobe (ATL), much less is known about the white matter connections underpinning this process. Sparse studies provided evidence for a possible role of the uncinate fasciculus, but the inferior longitudinal fasciculus (ILF) might also contribute, since it mainly projects into the ATL, interconnects it with the posterior lexical interface and is engaged in common name (CN) retrieval. To ascertain this hypothesis, we assessed 58 patients having undergone a neurosurgery for a left low-grade glioma by means of a famous face naming (FFN) task. The behavioural data were processed following a multilevel lesion approach, including location-based analyses, voxel-based lesion-symptom mapping (VLSM) and disconnection-symptom mapping. Different statistical models were generated to control for sociodemographic data, familiarity, biographical knowledge and control cognitive performances (i.e., semantic and episodic memory and CN retrieval). Overall, VLSM analyses indicated that damage to the mid-to-anterior part of the ventro-basal temporal cortex was especially associated with PN retrieval deficits. As expected, tract-oriented analyses showed that the left ILF was the most strongly associated pathway. Our results provide evidence for the pivotal role of the ILF in the PN retrieval network. This novel finding paves the way for a better understanding of the pathophysiological bases underlying PN retrieval difficulties in the various neurological conditions marked by white matter abnormalities.

Intraoperative functional remapping unveils evolving patterns of cortical plasticity.

The efficiency with which the brain reorganizes following injury not only depends on the extent and the severity of the lesion, but also on its temporal features. It is established that diffuse low-grade gliomas (DLGG), brain tumours with a slow-growth rate, induce a compensatory modulation of the anatomo-functional architecture, making this kind of tumours an ideal lesion model to study the dynamics of neuroplasticity. Direct electrostimulation (DES) mapping is a well-tried procedure used during awake resection surgeries to identify and spare cortical epicentres which are critical for a range of functions. Because DLGG is a chronic disease, it inevitably relapses years after the initial surgery, and thus requires a second surgery to reduce tumour volume again. In this context, contrasting the cortical mappings obtained during two sequential neurosurgeries offers a unique opportunity to both identify and characterize the dynamic (i.e. re-evolving) patterns of cortical re-arrangements. Here, we capitalized on an unprecedented series of 101 DLGG patients who benefited from two DES-guided neurosurgeries usually spaced several years apart, resulting in a large DES dataset of 2082 cortical sites. All sites (either non-functional or associated with language, speech, motor, somatosensory and semantic processing) were recorded in Montreal Neurological Institute (MNI) space. Next, we used a multi-step approach to generate probabilistic neuroplasticity maps that reflected the dynamic rearrangements of cortical mappings from one surgery to another, both at the population and individual level. Voxel-wise neuroplasticity maps revealed regions with a relatively high potential of evolving reorganizations at the population level, including the supplementary motor area (SMA, Pmax = 0.63), the dorsolateral prefrontal cortex (dlPFC, Pmax = 0.61), the anterior ventral premotor cortex (vPMC, Pmax = 0.43) and the middle superior temporal gyrus (STG Pmax = 0.36). Parcel-wise neuroplasticity maps confirmed this potential for the dlPFC (Fisher's exact test, PFDR-corrected = 6.6 × 10-5), the anterior (PFDR-corrected = 0.0039) and the ventral precentral gyrus (PFDR-corrected = 0.0058). A series of clustering analyses revealed a topological migration of clusters, especially within the left dlPFC and STG (language sites); the left vPMC (speech arrest/dysarthria sites) and the right SMA (negative motor response sites). At the individual level, these dynamic changes were confirmed for the dlPFC (bilateral), the left vPMC and the anterior left STG (threshold free cluster enhancement, 5000 permutations, family-wise error-corrected). Taken as a whole, our results provide a critical insight into the dynamic potential of DLGG-induced continuing rearrangements of the cerebral cortex, with considerable implications for re-operations.

Evidence for a critical role of the left inferior parietal lobule and underlying white matter connectivity in proficient text reading.

OBJECTIVE: Reading proficiency is an important skill for personal and socio-professional daily life. Neurocognitive models underlie a dual-route organization for word reading, in which information is processed by both a dorsal phonological "assembled phonology route" and a ventral lexical-semantic "addressed phonology route." Because proficient reading should not be reduced to the ability to read words one after another, the current study was designed to shed light on the neural bases specifically underpinning text reading and the relative contributions of each route to this skill. METHODS: Twenty-two patients with left-sided, diffuse, low-grade glioma who underwent operations while awake were included. They were divided into 3 groups on the basis of tumor location: the inferior parietal lobule (IPL) group (n = 6), inferior temporal gyrus (Tinf) group (n = 6), and fronto-insular (control) group (n = 10). Spoken language and reading abilities were tested in all patients the day before surgery, during surgery, and 3 months after surgery, and cognitive functioning was evaluated before and 3 months after surgery. Text-reading scores obtained before and 3 months after surgery were compared within each group and between groups, correlations between reading scores and both spoken language and cognitive scores were calculated, postoperative cortical-subcortical resection location was estimated, and multiple regression analysis was conducted to examine the relationship between reading proficiency and lesion location. RESULTS: The results indicated that only the patients in the IPL group showed a significant decrease in text-reading scores between periods, which was not associated with lower scores in naming or verbal fluency; patients in the Tinf group showed a slight nonsignificant decrease in text reading between periods, which was associated with a clear decrease in naming and semantic verbal fluency; and patients in the control group showed no differences between preoperative and postoperative reading and spoken language scores. The results of the analysis of these behavioral results and anatomical data (resection cavities and white matter damage) suggest critical roles for the left inferior parietal lobule and underlying white matter connectivity, especially the posterior segment of the arcuate fasciculus, in proficient text reading. CONCLUSIONS: Text-reading proficiency may depend on not only the integrity of both processing routes but also their capacity for interaction, with critical roles for the left inferior parietal lobule and posterior arcuate fasciculus. These findings have fundamental as well as clinical implications.

Precuneal gliomas promote behaviorally relevant remodeling of the functional connectome.

OBJECTIVE: The precuneus hosts one of the most complex patterns of functional connectivity in the human brain. However, due to the extreme rarity of neurological lesions specifically targeting this structure, it remains unknown how focal damage to the precuneus may impact resting-state functional connectivity (rsFC) at the brainwide level. The aim of this study was to investigate glioma-induced rsFC modulations and to identify patterns of rsFC remodeling that accounted for the maintenance of cognitive performance after awake-guided surgical excision. METHODS: In a unique series of patients with IDH1-mutated low-grade gliomas (LGGs) infiltrating the precuneus who were treated at a single neurosurgical center (Montpellier University Medical Center, 2014-2021), the authors gauged the dynamic modulations induced by tumors on rsFC in comparison with healthy participants. All patients received a preoperative resting-state functional MRI and underwent operation guided by awake cognitive mapping. Connectome multivariate pattern analysis (MVPA), seed-network analysis, and graph theoretical analysis were conducted and correlated to executive neurocognitive scores (i.e., phonological and semantic fluencies, Trail-Making Test [TMT] parts A and B) obtained 3 months after surgery. RESULTS: Seventeen patients with focal precuneal infiltration were selected (mean age 38.1 ± 11.2 years) and matched to 17 healthy participants (mean age 40.5 ± 10.4 years) for rsFC analyses. All patients underwent awake cognitive mapping, allowing total resection (n = 3) or subtotal resection (n = 14), with a mean extent of resection of 90.6% ± 7.3%. Using MVPA (cluster threshold: p-false discovery rate corrected < 0.05, voxel threshold: p-uncorrected < 0.001), remote hotspots with significant rsFC changes were identified, including both insulas, the anterior cingulate cortex, superior sensorimotor cortices, and both frontal eye fields. Further seed-network analyses captured 2 patterns of between-network redistribution especially involving hyperconnectivity between the salience, visual, and dorsal attentional networks. Finally, the global efficiency of the salience-visual-dorsal attentional networks was strongly and positively correlated to 3-month postsurgical scores (n = 15) for phonological fluency (r15 = 0.74, p = 0.0027); TMT-A (r15 = 0.65, p = 0.012); TMT-B (r15 = 0.70, p = 0.005); and TMT-B-A (r15 = 0.62, p = 0.018). CONCLUSIONS: In patients with LGGs infiltrating the precuneus, remote and distributed functional connectivity modulations in the preoperative setting are associated with better maintenance of cognitive performance after surgery. These findings provide a new vision of the mechanistic principles underlying neural plasticity and cognitive compensation in patients with LGGs.

Constant Multi-Tasking With Time Constraint to Preserve Across-Network Dynamics Throughout Awake Surgery for Low-Grade Glioma: A Necessary Step to Enable Patients Resuming an Active Life.

Awake surgery for brain gliomas improves resection while minimizing morbidity. Although intraoperative mapping was originally used to preserve motor and language functions, the considerable increase of life expectancy, especially in low-grade glioma, resulted in the need to enhance patients' long-term quality of life. If the main goal of awake surgery is to resume normal familial and socio-professional activities, preventing hemiparesis and aphasia is not sufficient: cognitive and emotional functions must be considered. To monitor higher-order functions, e.g., executive control, semantics or mentalizing, further tasks were implemented into the operating theater. Beyond this more accurate investigation of function-specific neural networks, a better exploration of the inter-system communication is required. Advances in brain connectomics led to a meta-network perspective of neural processing, which emphasizes the pivotal role of the dynamic interplay between functional circuits to allow complex and flexible, goal-directed behaviors. Constant multi-tasking with time constraint in awake patients may be proposed during intraoperative mapping, since it provides a mirror of the (dys)synchronization within and across neural networks and it improves the sensitivity of behavioral monitoring by increasing cognitive demand throughout the resection. Electrical mapping may hamper the patient to perform several tasks simultaneously whereas he/she is still capable to achieve each task in isolation. Unveiling the meta-network organization during awake mapping by using a more ecological multi-demand testing, more representative of the real-life conditions, constitutes a reliable way to tailor the surgical onco-functional balance based upon the expectations of each patient, enabling him/her to resume an active life with long-lasting projects.

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

BACKGROUND: Reoperations in patients with recurrent low-grade gliomas (RLGG) were proposed to control tumor residual and delay the risk of malignant transformation over time. OBJECTIVE: To investigate neurocognitive outcomes in patients with RLGG who underwent a second surgery with awake monitoring. METHODS: In this retrospective study, patients who underwent a second awake surgery for RLGG were included. Patients had presurgical and 3-mo postsurgical neuropsychological assessments. Data were converted into Z-scores and combined by the cognitive domain. Number of patients with cognitive deficits (Z-score <-1.65), variations of Z-scores, and extent of resection (EOR) were analyzed. RESULTS: Sixty-two patients were included (mean age: 41.2 ± 10.0 yr). None had permanent neurological deficits postoperatively. Eight patients (12.9%) had a cognitive deficit preoperatively. Four additional patients (6.5%) had a cognitive deficit 3 mo after reoperation. Among other patients, 13 (21.0%) had a mild decline without cognitive deficits while 29 (46.8%) had no change of their performances and 8 (12.9%) improved. Overall, 94.2% of the patients returned to work. There were no correlations between EOR and Z-scores. Total/subtotal resections were achieved in 91.9% of the patients (mean residual: 3.1 cm3). Fifty-eight patients (93.5%) were still alive after an overall follow-up of 8.3 yr. CONCLUSION: Reoperation with awake monitoring in patients with RLGG was compatible with an early recovery of neuropsychological abilities. Four patients (6.5%) presented a new cognitive deficit at 3 mo postoperatively. Total/subtotal resections were achieved in most patients. Based on these favorable outcomes, reoperation should be considered in a more systematic way.

Cognitive preservation following awake mapping-based neurosurgery for low-grade gliomas: A longitudinal, within-patient design study.

BACKGROUND: Awake surgery with intraoperative electrical mapping emerged as a gold-standard approach in newly diagnosed diffuse low-grade glioma (DLGG) to optimize the extent of resection (EOR) while sparing critical brain structures. However, no study has assessed to what extent cognitive recovery occurs following awake mapping-guided neurosurgery in a large, longitudinal, and homogeneous series of DLGG. METHODS: A longitudinal study on the cognitive status of 157 DLGG patients was performed. Neuropsychological assessments were done before and three months after awake mapping-based surgery. Z-scores and variations of Z-scores were computed to determine the number of patients with cognitive deficit(s) or decline. Clinical, surgical, and histopathological variables were studied to investigate factors contributing to neurocognitive outcomes. RESULTS: Eighty-seven patients (55.4%) had preoperative cognitive impairments. Statistical analysis between the preoperative (baseline) and postoperative assessments demonstrated a significant difference in three domains (Executive, Psychomotor Speed and Attention, Verbal Episodic Memory). Eighty-six percent of patients exhibited no postoperative cognitive decline, and among them, 10% exhibited cognitive improvement. The mean EOR was 92.3%±7.8%. The EOR, postoperative volume, and tumor lateralization had a significant association with cognitive decline. No patients demonstrated permanent postoperative neurologic deficits, but 5.8% did not resume their preoperative professional activities. The 5-year survival rate was 82.2%. CONCLUSIONS: This is the largest series ever reported with systematic longitudinal neuropsychological assessment. 86% of patients demonstrated no cognitive decline despite large resections and only 5.8% did not return to work. This work supports the practice of awake surgery with cognitive mapping as safe and effective in DLGG patients.

Jargonaphasia as a disconnection syndrome: A study combining white matter electrical stimulation and disconnectome mapping.

BACKGROUND: In jargonaphasia, speech is fluent but meaningless. While neuropsychological evaluation may distinguish a neologistic component characterised by non-word production and a semantic component where pronounced words are real but speech is senseless, how this relates to the underlying white matter anatomy is debated. OBJECTIVE: To identify white matter pathways causally involved in jargonaphasia. METHODS: We retrospectively screened the intraoperative brain mapping data of 571 awake oncological resections using direct cortico-subcortical electrostimulation. Jargonaphasia was induced in 17 patients (19 sites) during a naming task. Stimulation sites were normalized to the Montreal Neurological Institute template space and used to generate individual disconnectome maps. Non-parametric voxelwise one and two sample t-tests were performed to identify the underlying white matter anatomy. RESULTS: Jargonaphasia was induced only during stimulation of the left hemisphere. No cortical stimulation generated jargonaphasia. Subcortical sites causally associated with jargonaphasia clustered in 3 regions: in the temporal lobe (middle to inferior temporal gyri; n = 12), in the parietal lobe (supramarginal gyrus; n = 3) and in the temporal stem (n = 4). Disconnectome analysis indicated the inferior-fronto-occipital fasciculus (IFOF) was damaged in both neologistic and semantic jargonaphasia, while the involvement of the arcuate fasciculus was specific to neologistic jargonaphasia. CONCLUSION: For the first time, we show that jargonaphasia is induced by white matter stimulation, hinting at disconnection. As IFOF disconnection unites both variants, these may represent a continuum of disorders distinguished by semantic impairment. Conversely, damage to the arcuate fasciculus in addition to the IFOF is specific to neologistic jargonaphasia, thus suggesting a dual-disconnection syndrome.

White matter disconnectivity fingerprints causally linked to dissociated forms of alexia.

For over 150 years, the study of patients with acquired alexia has fueled research aimed at disentangling the neural system critical for reading. An unreached goal, however, relates to the determination of the fiber pathways that root the different visual and linguistic processes needed for accurate word reading. In a unique series of neurosurgical patients with a tumor close to the visual word form area, we combine direct electrostimulation and population-based streamline tractography to map the disconnectivity fingerprints characterizing dissociated forms of alexia. Comprehensive analyses of disconnectivity matrices establish similarities and dissimilarities in the disconnection patterns associated with pure, phonological and lexical-semantic alexia. While disconnections of the inferior longitudinal and posterior arcuate fasciculi are common to all alexia subtypes, disconnections of the long arcuate and vertical occipital fasciculi are specific to phonological and pure alexia, respectively. These findings provide a strong anatomical background for cognitive and neurocomputational models of reading.

Language recovery through a two-stage awake surgery in an aphasic patient with a voluminous left fronto-temporo-insular glioma: case report.

Awake surgery is difficult in glioma patients with preoperative aphasia. A 29-year-old right-handed bilingual (Spanish/English) patient experienced intractable seizures with severe language disorders due to a voluminous left fronto-temporo-insular tumor. We performed awake procedure with initial laborious language mapping, but with real-time improvement throughout the debulking, allowing preservation of the connectivity. A substantial residue was left. Postoperative cognitive rehabilitation resulted in a dramatic functional improvement, in both languages, permitting a complementary awake surgery, this time with a perfect collaboration of the patient. This multistep strategy enabled 92% of resection while enhancing quality of life with language recovery and epilepsy control.

Disrupting self-evaluative processing with electrostimulation mapping during awake brain surgery.

Brain awake surgery with cognitive monitoring for tumor removal has become a standard of treatment for functional purpose. Yet, little attention has been given to patients' interpretation and awareness of their own responses to selected cognitive tasks during direct electrostimulation (DES). We aim to report disruptions of self-evaluative processing evoked by DES during awake surgery. We further investigate cortico-subcortical structures involved in self-assessment process and report the use of an intraoperative self-assessment tool, the self-confidence index (SCI). Seventy-two patients who had undergone awake brain tumor resections were selected. Inclusion criteria were the occurrence of a DES-induced disruption of an ongoing task followed by patient's failure to remember or criticize these impairments, or a dissociation between patient's responses to an ongoing task and patient's SCI. Disruptions of self-evaluation were frequently associated with semantic disorders and critical sites were mostly found along the left/right ventral semantic streams. Disconnectome analyses generated from a tractography-based atlas confirmed the high probability of the inferior fronto-occipital fasciculus to be transitory 'disconnected'. These findings suggest that white matters pathways belonging to the ventral semantic stream may be critically involved in human self-evaluative processing. Finally, the authors discuss the implementation of the SCI task during multimodal intraoperative monitoring.

Homotopic redistribution of functional connectivity in insula-centered diffuse low-grade glioma.

OBJECTIVE: In the event of neural injury, the homologous contralateral brain areas may play a compensatory role to avoid or limit the functional loss. However, this dynamic strategy of functional redistribution is not clearly established, especially in the pathophysiological context of diffuse low-grade glioma. Our aim here was to assess the extent to which unilateral tumor infiltration of the insula dynamically modulates the functional connectivity of the contralesional one. METHODS: Using resting-state functional connectivity MRI, a seed-to-ROI approach was employed in 52 insula-centered glioma patients (n = 30 left and 22 right) compared with 19 age-matched healthy controls. RESULTS: Unsurprisingly, a significant decrease of the inter-insular connectivity was observed in both patient groups. More importantly, the analyses revealed a significant increase of the contralesional insular connectivity towards both cerebral hemispheres, especially in cortical areas forming the visual and the sensorimotor networks. This functional redistribution was not identified when the analyses were performed on three control regions for which the homologous area was not impaired by the tumor. This overall pattern of results indicates that massive infiltration of the insular cortex causes a significant redeployment of the contralesional functional connectivity. CONCLUSION: This general finding suggests that the undamaged insula plays a role in the functional compensation usually observed in this patient population, and thus provides compelling support for the concept of homotopic functional plasticity in brain-damaged patients.

Planning Brain Tumor Resection Using a Probabilistic Atlas of Cortical and Subcortical Structures Critical for Functional Processing: A Proof of Concept.

BACKGROUND: Functional preoperative planning for resection of intrinsic brain tumors in eloquent areas is still a challenge. Predicting subcortical functional framework is especially difficult. Direct electrical stimulation (DES) is the recommended technique for resection of these lesions. A reliable probabilistic atlas of the critical cortical epicenters and subcortical framework based on DES data was recently published. OBJECTIVE: To propose a pipeline for the automated alignment of the corticosubcortical maps of this atlas with T1-weighted MRI. METHODS: To test the alignment, we selected 10 patients who underwent resection of brain lesions by using DES. We aligned different cortical and subcortical functional maps to preoperative volumetric T1 MRIs (with/without gadolinium). For each patient we quantified the quality of the alignment, and we calculated the match between the location of the functional sites found at DES and the functional maps of the atlas. RESULTS: We found an accurate brain extraction and alignment of the functional maps with both the T1 MRIs of each patient. The matching analysis between functional maps and functional responses collected during surgeries was 88% at cortical and, importantly, 100% at subcortical level, providing a further proof of the correct alignment. CONCLUSION: We demonstrated quantitatively and qualitatively the reliability of this tool that may be used for presurgical planning, providing further functional information at the cortical level and a unique probabilistic prevision of distribution of the critical subcortical structures. Finally, this tool offers the chance for multimodal planning through integrating this functional information with other neuroradiological and neurophysiological techniques.

Neuropsychological assessments before and after awake surgery for incidental low-grade gliomas.

OBJECTIVE: Early surgery in presumed asymptomatic patients with incidental low-grade glioma (ILGG) has been suggested to improve maximal resection rates and overall survival. However, no study has reported on the impact of such preventive treatment on cognitive functioning. The aim of this study was to investigate neuropsychological outcomes in patients with ILGG who underwent preventive surgery. METHODS: This was a retrospective analysis of a consecutive series of patients with ILGG who underwent awake surgery and who had presurgical and 3-month postsurgical neuropsychological assessments. Data were normalized into z-scores and regrouped by cognitive domains. Clinicoradiological data, histomolecular profile, and differences in z-scores (Δz-scores) were analyzed. RESULTS: Forty-seven patients were included (mean age 39.2 ± 11.3 years). Twenty-eight patients (59.6%) underwent supratotal or total resections. All patients were still alive after a mean follow-up of 33.0 ± 30.8 months. Forty-one patients (87.2%) had stable (n = 34, 72.3%) or improved (Δz-score > 1; n = 7, 14.9%) neurocognitive outcomes after surgery. Six patients (12.8%) presented a slight impairment (Δz-score < -1) in at least one cognitive domain. The mean presurgical and postsurgical z-scores were comparable except in the psychomotor speed and attention domain. A significant correlation between presurgical executive functioning and tumor volume was reported, whereas the extent of resection and histomolecular profile did not impact neuropsychological outcomes. CONCLUSIONS: Early surgical treatment in presumed asymptomatic patients with ILGG was associated with stable or improved neuropsychological outcomes in 87.2% of patients at 3 months, with only mild cognitive decline observed in 6 patients. In return, supratotal or total resections were achieved in most patients, and all patients were still alive at the end of the follow-up.

Presence of a translator in the operating theater for awake mapping in foreign patients with low-grade glioma: a surgical experience based on 18 different native languages.

OBJECTIVE: Intraoperative brain mapping with neurocognitive monitoring during awake surgery is currently the standard pattern of care for patients with diffuse low-grade glioma (DLGG), allowing a maximization of the extent of resection (EOR) while preserving quality of life. This study evaluated the feasibility of DLGG resections performed with intraoperative cognitive monitoring via the assistance of a translator for patients speaking foreign languages, and compared the surgical functional and oncological outcomes according to the possibility of direct communication with the surgical team. METHODS: Foreign patients who underwent awake surgery with intraoperative electrical mapping with the assistance of a translator for the resection of a DLGG in the authors' institution between January 2010 and December 2020 were included. Patients whose native language included one of the three languages spoken by the surgical team (i.e., French, English, or Spanish) were excluded. The patients were classified into two groups. Group 1 was composed of patients able to communicate in at least one of these three languages in addition to their own native language. Group 2 was composed of patients who spoke none of these languages, and therefore were unable to communicate directly with the operating staff. The primary outcome was the patients' ability to return to work 3 months after surgery. RESULTS: Eighty-four patients were included, of whom 63 were classified in group 1 and 21 in group 2. Eighteen different native languages were tested in the operating theater. Awake mapping was successful, with elicitation of transitory disturbances in all patients. There was no significant difference in the 3-month return-to-work status between the two groups (95% in group 1 [n = 58/61] vs 88% in group 2 [n = 15/17]; p = 0.298). Similarly, no significant difference between the two groups was found regarding the intraoperative tasks performed, the mean duration of the surgery, and the rate of permanent postoperative deficit. A significantly greater EOR was observed in group 1 patients in comparison to group 2 patients (90.4% ± 10.6% vs 87.7% ± 6.1%; p = 0.029). CONCLUSIONS: Real-time translation by an interpreter during awake resection of glioma is feasible and safe in foreign patients. Nonetheless, when no direct verbal communication is possible between the surgical team and the patient, the EOR is less.

Network-behavior mapping of lasting executive impairments after low-grade glioma surgery.

Executive functions (EF) may be significantly impaired following low-grade glioma (LGG) surgery, especially in the event of white matter (WM) disruption. The aim of this study was to identify the connective tracts associated with EF impairments after LGG surgery, and to provide new insights into the WM network architecture of EF. EF measurements were collected in 270 patients at the chronic postoperative phase. This comprised cognitive flexibility, verbal inhibition and fluency abilities (phonological and categorical). The scores were z-corrected for age and educational level, and further submitted to a principal component analysis (PCA). Tracwise and disconnectome-behavior analyses were then performed using EF measures independently but also the extracted components from PCA. For the first analyses, 15 tracts of interest were selected. Two principal components were extracted from the behavioral data, interpreted as 'EF' and 'language' components. Robust, bonferroni-corrected correlations were established between the EF component and Layers II and III of the left superior longitudinal fasciculus, and between phonological fluency/inhibition and the same tracts. Less powerful but still significant correlations were also observed with the left frontal aslant and fronto-striatal tracts. These results were confirmed by disconnectome-behavior analyses. Our results indicate that surgically-related disruption of the fronto-parietal and the frontal cortico-subcortical connectivity, and of the frontal aslant tract, is related to long-lasting EF impairments. In addition to providing new insights into the WM pathways supporting EF, these findings are especially useful for both surgical planning and the predictive approach of neuropsychological disorders in the context of LGG surgery.