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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.

Few studies addressed the evolution of brain activity before and after brain tumor resection. Using a fMRI naming task, we evaluated possible underlying plasticity phenomena. Thirty-two patients with left low-grade gliomas (16 women; age = 38.6 ± 8.31 years) and 19 healthy controls (7 women; age = 42.4 ± 12.1) were included in the study. An overt picture-naming task (DO80) was performed pre and post (3 months) surgery, as well as within the MRI in a covert manner. Exams included an injected 3DT1, a T2FLAIR, a DTI and a GE-EPI (task) sequence. Activations maps were compared with picture naming score, FA and MD maps were estimated, a VLSM analysis was performed on tumor masks, and disconnectome maps were reconstructed. Pre-surgery, the left parahippocampal gyrus (LPH) was inversely associated with task performance. Increased pre-post surgery left lingual gyrus (LLG) activity was found related to decreased picture naming performance. The evolution of left lingual gyrus (LLG) activity was negatively associated with the evolution of picture naming performance. In controls, the LPH was functionally connected to the right precentral gyrus (RPCG) and slightly to the LLG. This was not clearly retrieved in the patient group. Preoperatively, the LLG was connected to the left planum temporale and to the right lingual gyrus. The same result was found for controls. Postoperatively, the LLG was only connected to the RPCG. No association was found between evolution of FA/MD and evolution of picture naming performance. There is not one unique pattern of pre- and postoperative plasticity concerning picture-naming performance in DLGG patients.

Negative motor responses (NMRs) are defined as movement arrests induced by direct electrical stimulation of the brain. The NMRs manifest themselves after the disruption of a corticosubcortical network involved in motor control, referred to as the 'negative motor network'. At present, the spatial topography of the negative motor areas (NMAs) is poorly known. Hence, the objectives of the present study were to establish the first probabilistic map of the NMAs of the upper limbs and face, identify potential subareas, and investigate the NMAs' relationships with the primary motor cortex. A total of 117 patients with low grade glioma underwent awake surgery with direct electrostimulation. The Montreal Neurological Institute coordinates of sites eliciting NMRs (face and upper limbs) were registered. A probabilistic map was created, and subareas were identified in a cluster analysis. Each cluster was then plotted on the Glasser atlas and the 1200 Subjects Group Average Data from the Human Connectome Project, in order to study connectivity and compare the results with recent parcellation data. We elicited 386 NMRs (mean ± standard deviation current intensity: 2.26 ± 0.5 mA) distributed throughout the precentral gyrus in both hemispheres. In each hemisphere, we found two clusters for facial NMRs. For upper limb NMRs, we found two clusters in the right hemisphere; and three in the left. Each cluster overlapped with parcellations from the Glasser atlas. For the face, the NMAs were associated with areas 55b and 6v. For the upper limbs, the NMAs were linked to areas 6v, 6d, and 55b. Each NMA cluster showed a specific pattern of functionally connected areas, such as the inferior frontal gyrus, supplementary motor area, parietal areas, and posterior superior temporal gyrus. The white matter pathways projecting to these subareas involved the frontal aslant tract and the frontostriatal tract-both of which are well known to be associated with NMRs. This study constitutes the largest series to date of NMRs mapped to the lateral surface of both hemispheres. Rather than being randomly distributed, the NMAs appeared to be well structured and corresponded to parcellations identified by functional neuroimaging. Moreover, the white matter pathways known to drive NMRs are also connected to regions encompassing NMAs. Taken as a whole, our results suggest that NMAs belong to a large-scale modulatory motor network. Our new probabilistic map might constitute a valuable tool for use in further clinical and fundamental studies of motor control., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: The present study aimed to elucidate the neural correlates of the deafferentation cognitive model of verbal perseveration (VP) by analyzing the connectomics of the sites where electric stimulation elicited VP during awake left glioma surgery., Methods: We retrospectively reviewed the anatomic sites that generated VP when electrically stimulated in a series of 21 patients operated on while awake for a left glioma. Each stimulation point was manually located on the postoperative MRI and then registered to the Montreal Neurological Institute template. Connectomics of these sites were further analyzed with Tractotron and disconnectome maps., Results: VP stimulation sites were located within the white matter surrounding the posterosuperior head of the caudate nucleus, as well as within the white matter of the external capsule and the superolateral wall of the temporal horn of the ventricle. Furthermore, Tractotron and disconnectome maps revealed the connectome of these stimulation sites: the inferior fronto-occipital fasciculus, frontostriatal tract, and anterior thalamic radiations., Conclusion: On the basis of these results and other data, we propose the following anatomic implementation of the deafferentation cognitive model: the lexico-semantic system, comprising different areas linked together through direct cortico-cortical connections, sends information to the striatum; the striato-thalamic system acts as a tunable filter of this lexico-semantic input; and the thalamus projects back to the lexico-semantic system, amplifying the targeted response and inhibiting its competitors., (© 2019 American Academy of Neurology.)

Objectives: To validate the functional relevance of resting state networks (RSNs) by means of a comparison of resting state connectivity (RSC) between language regions elicited by direct cortical stimulation versus RSC between random regions; and to evaluate the accuracy of resting state fMRI in surgical planning by assessing the overlap between RSNs and intraoperative functional mapping results., Methods: Sensorimotor and language eloquent sites were identified by direct electrical cortical stimulation in 98 patients with a diffuse low-grade glioma. A seed to voxel analysis with inter-language stimulation point connectivity versus inter-random ROIs connectivity was performed (19 patients). An independant component analysis (ICA) was also applied to rsfMRI data. Language and sensorimotor components were selected over 20 independent components and compared to the corresponding stimulation points and resected cortex masks (31 and 90 patients, respectively)., Results: Mean connectivity value between language seeds was significantly higher than the one between random seeds (0.68 ± 0.39 and 0.12 ± 0.21 respectively, P < 10 -10 ). 96 ± 11% of sensorimotor stimulation points were located within 10 mm from sensorimotor ICA maps versus 92 ± 21% for language. 3.1 and 15% of resected cortex overlapped sensorimotor and language networks, respectively. Mean sensorimotor stimulation points and resected cortex z-scores were 2.0 ± 1.2 and -0.050 ± 0.60, respectively (P < 10 -10 ). Mean language stimulation points and resected cortex z-scores were 1.6 ± 1.9 and 0.68 ± 0.91, respectively, P < 0.005., Conclusion: The significantly higher RSC between language seeds than between random seeds validated the functional relevance of RSC. ICA partly succeeded to distinguish eloquent versus surgically removable areas and may be possibly used as a complementary tool to intraoperative mapping. Hum Brain Mapp 37:3721-3732, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objectives: To ascertain the neural network mediating reading using intraoperative electrostimulation., Experimental Design: A cortical and axonal intraoperative electrical mapping of reading processes was achieved in seven patients who underwent awake surgery for a left occipitotemporal glioma. We performed resection cavity overlapping and superimposition with a diffusion tensor imaging-based white matter atlas. We assessed the relationship between the location of resection cavities and the occurrence of reading impairments of regular, irregular, and pseudowords., Principal Observations: Intraoperative stimulation of the left posterior inferior temporal cortex (ITCp) elicited reading disturbances. Subcortical stimulation at the anterior portion of the visual word form area (VWFA) induced addressed phonology (irregular words reading) disturbances. Subcortical stimulation of the connection between VWFA and the posterior segment of the arcuate fascicle (AFp) induced both addressed and assembled phonology (irregular and pseudowords reading) disturbances. Postoperative assessment showed that resection of the posterior portion of the inferior longitudinal fascicle (ILFp), connecting the visual cortex to VWFA, induced long-term and global reading impairment. Resection of the terminations of left AFp in the ITCp-induced irregular and pseudowords reading disturbances with no impairment of regular words reading. Resection of the anterior portion of ILF did not induce reading impairment., Conclusions: Our data support an inner posterior-to-anterior hierarchical coding of letter strings in the VWFA and a crucial role of the left ILFp to provide visual inputs to the VWFA. Furthermore, we suggest that the AFp is involved in an interactive feedback system between visual and nonvisual information, recruited when reading irregular and pseudowords., (© 2015 Wiley Periodicals, Inc.)

Human empathic experience is a multifaceted psychological construct which arises from functional integration of multiple neural networks. Despite accumulating knowledge about the cortical circuitry of empathy, almost nothing is known about the connectivity that may be concerned in conveying empathy-related neural information. To bridge this gap in knowledge, we studied dispositional empathy in a large-sized cohort of 107 patients who had undergone surgery for a diffuse low-grade glioma. The self-report questionnaire used enabled us to obtain a global measure of subjective empathy but also, importantly, to assess the two main components of empathy (cognitive and emotional). Data were processed by combining voxelwise and tractwise lesion-symptom analyses. Several major findings emerged from our analyses. First of all, topological voxelwise analyses were inconclusive. Conversely, tractwise multiple regression analyses, including all major associative white matter pathways as potential predictors, yielded to significant models explaining substantial part of the behavioural variance. Among the main results, we found that disconnection of the left cingulum bundle was a strong predictor of a low cognitive empathy (p<0.0005 Bonferroni-corrected). Similarly, we found that disconnection of the right uncinate fasciculus and the right inferior fronto-occipital fasciculus predicted, respectively, a low (p<0.05 Bonferroni-corrected) and a high (p<0.05 Bonferroni-corrected) subjective empathy. Finally, although we failed to relate emotional empathy to disruption of a specific tract, correlation analyses indicated a positive association between this component of empathy and the volumes of residual lesion infiltration in the right hemisphere (p<0.01). Taken as a whole, these findings provide key fundamental insights into the anatomical connectivity of empathy. They may help to better understand the pathophysiology of empathy impairments in pathological conditions characterized by abnormalities of long-range anatomical connectivity, such as autism spectrum disorders, schizophrenia and fronto-temporal dementia., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Object: Preserving function while optimizing the extent of resection is the main goal in surgery for diffuse low-grade glioma (DLGG). This is particularly relevant for DLGG involving the sagittal stratum (SS), where damage can have severe consequences. Indeed, this structure is a major crossroad in which several important fascicles run. Thus, its complex functional anatomy is still poorly understood. Subcortical electrical stimulation during awake surgery provides a unique opportunity to investigate white matter pathways. This study reports the findings on anatomofunctional correlations evoked by stimulation during resection for gliomas involving the left SS. Surgical outcomes are also detailed., Methods: The authors performed a review of patients who underwent awake surgery for histopathologically confirmed WHO Grade II glioma involving the left SS in the neurosurgery department between August 2008 and August 2012. Information regarding clinicoradiological features, surgical procedures, and outcomes was collected and analyzed. Intraoperative electrostimulation was used to map the eloquent structures within the SS., Results: Eight consecutive patients were included in this study. There were 6 men and 2 women, whose mean age was 41.7 years (range 32-61 years). Diagnosis was made because of seizures in 7 cases and slight language disorders in 1 case. After cortical mapping, subcortical stimulation detected functional fibers running in the SS in all patients: semantic paraphasia was generated by stimulating the inferior frontooccipital fascicle in 8 cases; alexia was elicited by stimulating the inferior longitudinal fascicle in 3 cases; visual disorders were induced by stimulating the optic radiations in 5 cases. Moreover, in front of the SS, phonemic paraphasia was evoked by stimulating the temporal part of the arcuate fascicle in 5 patients. The resection was stopped according to these functional limits in the 8 patients. After a transient postsurgical worsening, all patients recovered to normal results on examination, except for the persistence of a right superior quadrantanopia in 5 cases, with no consequences for quality of life. The 8 patients returned to a normal social and professional life. Total or subtotal resection was achieved in all cases but one., Conclusions: The authors suggest that the use of intrasurgical electrical mapping of the white matter pathways in awake patients opens the door to extensive resection of DLGG within the left SS while preserving the quality of life. Further anatomical, clinical, radiological, and electrophysiological studies are needed for a better understanding of the functional anatomy of this complex region.

The subcortical connectivity underlying verbal perseveration (VP) remains poorly understood. We have previously reported that intraoperative electrical stimulation of the caudate nucleus during awake surgery resulted in VP. Here, our purpose is to study the white matter pathway underlying VP using subcortical stimulation mapping in a series of patients who underwent glioma resection. Eleven patients with a left hemispheric low grade glioma were operated on while awake. Intraoperative direct electrical stimulation was used both at cortical and subcortical levels while the patients carried out motor and naming tasks during the resection. All patients experienced VP during electrical stimulation performed at the level of different subcortical locations, which corresponded in the 11 cases to different parts of the left inferior fronto-occipital fascicle. Perseveration persisted into the postoperative days, but resolved completely by three months.Our original findings provide further insight into the neuroanatomical basis of VP, by supporting the role of left inferior fronto-occipital fascicle. Such data may have both fundamental and clinical implications.

From recent findings provided by brain stimulation mapping during picture naming, we re-examine the neural basis of language. We studied structural-functional relationships by correlating the types of language disturbances generated by stimulation in awake patients, mimicking a transient virtual lesion both at cortical and subcortical levels (white matter and deep grey nuclei), with the anatomical location of the stimulation probe. We propose a hodotopical (delocalized) and dynamic model of language processing, which challenges the traditional modular and serial view. According to this model, following the visual input, the language network is organized in parallel, segregated (even if interconnected) large-scale cortico-subcortical sub-networks underlying semantic, phonological and syntactic processing. Our model offers several advantages (i) it explains double dissociations during stimulation (comprehension versus naming disorders, semantic versus phonemic paraphasias, syntactic versus naming disturbances, plurimodal judgment versus naming disorders); (ii) it takes into account the cortical and subcortical anatomic constraints; (iii) it explains the possible recovery of aphasia following a lesion within the "classical" language areas; (iv) it establishes links with a model executive functions., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Accessing the meaning of words, objects, people and facts is a human ability, made possible thanks to semantic processing. Although studies concerning its cortical organization are proficient, the subcortical connectivity underlying this semantic network received less attention. We used intraoperative direct electrostimulation, which mimics a transient virtual lesion during brain surgery for glioma in eight awaken patients, to map the anatomical white matter substrate subserving the semantic system. Patients performed a picture naming task and a non-verbal semantic association test during the electrical mapping. Direct electrostimulation of the inferior fronto-occipital fascicle, a poorly known ventral association pathway which runs throughout the brain, induced in all cases semantic disturbances. These transient disorders were highly reproducible, and concerned verbal as well as non-verbal output. Our results highlight for the first time the essential role of the left inferior fronto-occipital fascicle in multimodal (and not only in verbal) semantic processing. On the basis of these original findings, and in the lights of phylogenetic considerations regarding this fascicle, we suggest its possible implication in the monitoring of the human level of consciousness related to semantic memory, namely noetic consciousness., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Object: It has been demonstrated that an extensive resection (total or subtotal) may significantly increase the overall survival in patients with WHO Grade II gliomas (low-grade gliomas [LGGs]). Yet, recent data have shown that conventional MR imaging underestimates the spatial extent of LGG, since tumor cells were found up to 20 mm around MR imaging abnormalities. Thus, it was hypothesized that an extended resection with a margin beyond MR imaging-defined abnormalities-a "supratotal" resection-might improve the outcome of LGG. However, because of the frequent location of LGG within "eloquent" brain areas, it is often difficult to achieve such a supratotal resection. This could nevertheless be possible when LGGs involve "noneloquent" areas, even in the left dominant hemisphere. The authors report on their use of awake electrical mapping to tailor the resection according to functional boundaries, that is, to pursue the resection beyond MR imaging-defined abnormalities, until corticosubcortical eloquent structures are encountered. Their aim was to apply this reliable surgical technique to LGGs located not within eloquent areas but distant from eloquent areas, to take a margin around the LGG visible on MR imaging while preserving brain function., Methods: Fifteen right-handed patients with a total of 17 tumors underwent resection of WHO Grade II gliomas involving nonfunctional areas within the left dominant hemisphere. In all patients, seizures were the initial manifestation of the tumors. Awake surgery with intraoperative electrostimulation was performed in all cases. The resection was continued until the surgeon reached cortical and subcortical areas crucial for brain function, especially language, as defined by the intrasurgical electrical mapping. The extent of resection was evaluated on postoperative FLAIR-weighted MR images., Results: Despite transient neurological worsening in 60% of cases, all patients recovered and returned to a normal life. Seizure control was obtained in all patients with a decrease of antiepileptic drug therapy. Postoperative MR imaging showed that total resection was achieved in all 17 tumors and supratotal resection in 15. The average volume of the postoperative cavity (36.8 cm(3)) was significantly larger than the mean preoperative tumor volume (26.6 cm(3)) (p = 0.009). Neuropathological examination confirmed the diagnosis of WHO Grade II glioma in all cases. The mean duration of postoperative follow-up was 35.7 months (range 6-135 months). Only 4 of 15 patients experienced recurrence (without anaplastic transformation); the average time to recurrence in these cases was 38 months; radiotherapy was performed 6 years after the relapse in 1 case; no other patients received any adjuvant treatment. This series was compared with a control group of 29 patients who had "only" complete resection: anaplastic transformation was observed in 7 cases in the control group but not in any case in the series of patients who underwent supracomplete resection (p = 0.037). Furthermore, adjuvant treatment was administered in 10 patients in the control group compared with 1 patient who underwent supracomplete resection (p = 0.043)., Conclusions: These findings support the usefulness of awake surgery with intraoperative functional (language) mapping with the attempt to perform supratotal resection of LGGs involving noneloquent areas in the left hemisphere. Indeed, the extent of resection was significantly increased in all cases but 2, with no additional permanent deficit and with control of seizures in all patients. The goal of supracomplete resection is currently to delay the anaplastic transformation, even if it does not (yet) enable a cure.

Human brain pathways required for language processing are poorly known. A new white matter tract in humans, the middle longitudinal fascicle, has recently been anatomically determined by diffusion tensor imaging and suggested to be essential for language. Our aim is to determine the importance of the middle longitudinal fascicle for language processing. This study is based on 8 patients with glioma resection at least involving the superior temporal gyrus of the left dominant hemisphere. Language is systematically examined pre- and postoperatively at 3 months. Intraoperative electrostimulation is used to map cortical and subcortical structures as functional boundaries of the glioma resection, including those essential for language processing. The resections are extensive (on average 62 ml, ranging from 21 to 111 ml) and include a large part of the middle longitudinal fascicle in all patients. Intraoperatively, no interference with picture naming is observed by electrostimulation of the middle longitudinal fascicle, while in all patients the inferior fronto-occipital fascicle is identified by eliciting semantic paraphasia as functional boundary. Postoperatively, no new permanent language deficits are detected by systematic language examination. Therefore, we suggest that the middle longitudinal fascicle may participate but is not essential for language processing., (Copyright © 2010 Wiley-Liss, Inc.)

Neural foundations of syntactic gender processing remain poorly understood. We used electrostimulation mapping in nine right-handed awake patients during surgery for a glioma within the left hemisphere, to study whether the cortico-subcortical structures involved in naming versus syntactic gender processing are common or distinct. In French, the article determines the grammatical gender. Thus, the patient was asked to perform a picture naming task and to give the appropriate article for each picture, with and without stimulation. Cortical stimulation elicited reproducible syntactic gender disturbances in six patients, in the inferior frontal gyrus (three cases), and in the posterior middle temporal gyrus (three cases). Interestingly, no naming disorders were generated during stimulation of the syntactic sites, while cortical areas inducing naming disturbances never elicited grammatical gender errors when stimulated. Moreover, at the subcortical level, stimulation of the white matter lateral to the caudate nucleus induced gender errors in three patients, with no naming disorders. Using cortico-subcortical electrical mapping in awake patients, we demonstrate for the first time (1) a double dissociation between syntactic gender and naming processing, supporting independent network model rather than serial theory, (2) the involvement of the left inferior frontal gyrus, especially the pars triangularis, and the posterior left middle temporal gyrus in grammatical gender processing, (3) the existence of white matter pathways, likely a sub-part of the left superior longitudinal fasciculus, underlying a large-scale distributed cortico-subcortical circuit which might selectively sub-serve syntactic gender processing, even if interconnected with parallel sub-networks involved in naming (semantic and phonological) processing., (Copyright © 2010 Wiley-Liss, Inc.)

Although studies on bilingualism are abundant, cognitive processes and neural foundations of language switching received less attention. The aim of our study is to provide new insights to this still open question: do dedicated region(s) for language switching exist or is this function underlain by a distributed circuit of interconnected brain areas, part of a more general cognitive system? On the basis of recent behavioral, neuroimaging, and brain stimulation studies, we propose an original 'hodological' model of language switching. This process might be subserved by a large-scale cortico-subcortical network, with an executive system (prefrontal cortex, anterior cingulum, caudate nucleus) controlling a more dedicated language subcircuit, which involves postero-temporal areas, supramarginal and angular gyri, Broca's area, and the superior longitudinal fasciculus.

Neurological insults that damage the left hemisphere are frequently associated with a variety of language disorders. Of these, lexical retrieval impairments are the most commonly observed, and often constitute the residual but lasting disturbance in patients with good functional outcomes. The current study was specifically designed to understand the anatomical factors that prevent full recovery of lexical retrieval in patients having undergone a neurosurgery for a left diffuse low-grade glioma, with a special focus on white matter disconnection. One hundred and ten patients operated on under local anaesthesia with intraoperative language mapping were included in this study. All benefited from an examination of language in the chronic phase using a picture-naming task. We derived from this task two well-controlled regressed measures of lexical retrieval based on the number of anomic responses and response times. We mapped the resection cavities and the postoperative residual lesion infiltrations (mainly located along the white matter tracts), and used a combination of voxelwise and tractwise lesion-deficit analyses to process the data. All results were corrected for multiple comparisons. For the purpose of comparison, 105 neurologically healthy control participants were further enrolled. At the cortical level, lexical retrieval impairments were mainly associated with resection of the mid-to-posterior part of the left inferior temporal gyrus, as revealed by standard voxel-based lesion-symptom analyses. Multilevel tractwise analyses, including correlations, ridge multiple regressions and group analyses, showed a strong involvement of the left inferior longitudinal fasciculus and, to a lesser extent, of the posterior superior longitudinal fasciculus. Further regression analyses indicated that lasting lexical retrieval impairments were better predicted by considering together both resection-related volume loss in the posterior inferior temporal gyrus and postoperative residual lesion volume in the left inferior longitudinal fasciculus. We conclude that the mid-to-posterior inferior temporal cortex and its underlying connections, especially the left inferior longitudinal fasciculus, are critical structures in the lexical retrieval network. Beyond this new insight, our data have important implications for both intraoperative language monitoring and rehabilitation strategies. [ABSTRACT FROM AUTHOR]