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.

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.

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.

Personality and behavioral changes after brain tumor resection: a lesion mapping study.

BACKGROUND: Cognitive functioning is generally well preserved in patients with diffuse low-grade glioma (DLGG), even in the case of extended tumor and resection. To date, the question of personality changes in these patients has received little attention. Our aim was to investigate to what extent certain aspects of personality and behaviors could be affected by DLGG resection. METHODS: We used self-reported personality questionnaires (NOEPI-R and TCI-R) and hetero-evaluation of executive behavioral changes in a large sample of 98 patients operated on for DLGG. To compare the patients' scores from the personality questionnaires, we recruited 47 healthy controls participants. To identify the putative neural networks associated with behavioral changes, a combination of voxel-wise and tract-wise lesion-symptom mapping was performed. RESULTS: First, results revealed no difference between patients and controls for each subdimension of the NOEPI-R. Regarding the TCI-R, the character dimensions and three out of four temperament dimensions did not differ. Second, behavioral changes (Irritability, Hypoactivity, Anticipative disorders, and disinterest) were reported between 40 and 50% of cases. Third, some personality dimensions (as neuroticism) were strongly predictive of postoperative behavioral disorders (as hypoactivity). Lastly, specific behavioral changes were associated with selective damage to cortical (left inferior frontal gyrus, supplementary motor area, and right fusiform gyrus) and white matter (left inferior fronto-occipital and uncinate fasciculi, right cingulum) structures. CONCLUSION: This study demonstrates that extensive lesions caused by DLGGs and their surgical resection have no or minor impact on patients' personality. However, specific personality dimensions are strongly predictive of behavioral disorders suggesting that the observed surgically related behavioral changes are modulated by the personality profile. Finally, the lesion mapping analyses indicate that damage to differential cortical or white matter structures leads to distinct patterns of behavioral abnormalities.

The antero-dorsal precuneal cortex supports specific aspects of bodily awareness.

The precuneus is a functionally heterogeneous area located on the medial face of the parietal cortex, wedged between the occipital cortex and the paracentral lobule. In view of its topological positioning, this associative cortex is well-placed to play an important role in multisensory integration, specific aspects of which participate to bodily awareness. However, this potential implication remains unestablished. We assessed bodily awareness longitudinally in 14 rare patients who underwent a surgery for a low-grade glioma mainly infiltrating the precuneus. To determine the brain locus the most frequently affected in patients showing bodily awareness disorders, we first contrasted the resection cavity distributions of patients with versus without bodily awareness disorders. We next applied 'lesion network mapping' to identify the networks functionally coupled with lesion locations causing bodily awareness disorder. Bodily awareness disorders were observed in half of patients after surgery, especially alien hand, macrosomatognosia and fading limb. Importantly, a dissociation was revealed between the antero-dorsal precuneus (bodily awareness disorders) and postero-dorsal precuneus (no bodily awareness disorders). Furthermore, bodily awareness disorder-related regions were specifically connected to a network of sensorimotor regions while others were connected with the default network. Altogether, the present findings indicate a critical role of the antero-dorsal precuneus in specific aspects of bodily awareness and in the maintenance of body schema.

Functional compensation of the left inferior longitudinal fasciculus for picture naming.

The role of the left inferior longitudinal fasciculus (ILF) in language processing has been called into question by recent studies showing that disruption of this tract in glioma patients did not necessarily lead to detrimental effects on spoken language, especially on picture naming. Here we show that disruption of the left ILF with axonal stimulation in patients undergoing an "awake" surgery for a slow-growing tumour systematically induces pure anomia, but only when the temporal pole (TP) is not infiltrated by the tumour. This finding not only confirms that the ILF plays a role in lexical retrieval in normal circumstances but also suggests that the information conveyed by this tract can be rerouted to alternative pathways when the TP is widely lesioned and abandons its function. This conclusion is further supported by the case of a patient who developed a long-lasting anomic aphasia after a surgically preplanned interruption of the ILF.

Preserved metacognitive ability despite unilateral or bilateral anterior prefrontal resection.

Brodmann area 10 (BA10) is thought to be at the summit of the prefrontal cortex's hierarchical organization. It is widely accepted that metacognitive abilities depend on the structural and functional properties of BA10. Our objective was to assess whether metacognition can be maintained after low-grade glioma surgery with BA10 resection. Three groups of participants were recruited: (i) patients having undergone resection of the right prefrontal cortex, including BA10 (n = 9); (ii) patients having undergone resection of the right prefrontal cortex but not BA10 (n = 10); and (iii) healthy controls (n = 38). Importantly, we also included a patient (referred to as "PR") with resection of BA10 in the two hemispheres. The patients with resection of right BA10 had metacognitive performances that were indistinguishable from those of brain-damaged control patients and healthy controls. Crucially, PR's metacognitive ability was not only maintained but was even in the upper quartile of normal performances. Our findings demonstrate that the brain can redistribute and remap metacognition in response to injury. We thus provide experimental evidence against the conventional hypothesis whereby cognitive functions are directly and lastingly linked to particular cortical structures. The latter hypothesis seems to be particularly false for the highest levels of human cognition and for BA10.

Individuals with pronounced schizotypal traits are particularly successful in tickling themselves.

We assessed self-tickling sensations in a group of participants high in schizotypal traits (n=27) and group of participants low in schizotypal traits (n=27). The groups were formed by screening a pool of 397 students for extreme scores in the French version of the Schizotypal Personality Questionnaire. As observed in a previous study involving psychiatric people with auditory hallucinations and/or passivity experiences our results showed that self-applied tactile stimulations are felt to be more ticklish by healthy individuals high in schizotypal traits. In contrast, there were no significant intergroup differences in the mean tickle rating in the externally-produced tickling condition. Furthermore, more successful self-tickling was associated with more frequent self-reports of unusual perceptual experiences (such as supernatural experiences) and passivity experiences in particular (such as a feeling of being under the control of an outside force or power).

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.

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.

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.

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.

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.

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.

Combining Electrostimulation With Fiber Tracking to Stratify the Inferior Fronto-Occipital Fasciculus.

The inferior fronto-occipital fasciculus (IFOF) is one of the longest association fiber tracts of the brain. According to the most recent anatomical studies, it may be formed by several layers, suggesting a role in multiple cognitive functions. However, to date, no attempt has been made to dissociate the functional contribution of the IFOF subpathways. In this study, real-time, cortico-subcortical mapping with direct electrostimulation was performed in 111 patients operated on in wide-awake surgery for a right low-grade glioma. Patients performed two behavioral tasks during stimulation, tapping, respectively, mentalizing and visual semantic cognition-two functions supposed to be partly mediated by the IFOF. Responsive white matter sites were first subjected to a clustering analysis to assess potential topological differences in network organization. Then they were used as seeds to generate streamline tractograms based on the HC1021 diffusion dataset (template-based approach). The tractograms obtained for each function were overlapped and contrasted to determine whether some fiber pathways were more frequently involved in one or the other function. The obtained results not only provided strong evidence for a role of the right IFOF in both functions, but also revealed that the tract is dissociable into two functional strata according to a ventral (semantic) and dorsal (mentalizing) compartmentalization. Besides, they showed a high degree of anatomo-functionnal variability across patients in the functional implication of the IFOF, possibly related to symmetrical/hemispheric differences in network organization. Collectively, these findings support the view that the right IFOF is a functionally multi-layered structure, with nevertheless interindividual variations.

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.

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.

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.

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.