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International audience; The angular gyrus (AG) has been described in numerous studies to be consistently activated in various functional tasks. The angular gyrus is a critical connector epicenter linking multiple functional networks due to its location in the posterior part of the inferior parietal cortex, namely at the junction between the parietal, temporal, and occipital lobes. It is thus crucial to identify the different pathways that anatomically connect this high-order association region to the rest of the brain. Our study revisits the three-dimensional architecture of the structural AG connectivity by combining state-of-the-art postmortem blunt microdissection with advanced in vivo diffusion tractography to comprehensively describe the association, projection, and commissural fibers that connect the human angular gyrus. AG appears as a posterior “angular stone” of associative connections belonging to mid- and long-range dorsal and ventral fibers of the superior and inferior longitudinal systems, respectively, to short-range parietal, occipital, and temporal fibers, including U-shaped fibers in the posterior transverse system. Thus, AG is at a pivotal dorso-ventral position reflecting its critical role in the different functional networks, particularly in language elaboration and spatial attention and awareness in the left and right hemispheres, respectively. We also reveal striatal, thalamic, and brainstem connections and a typical inter-hemispheric homotopic callosal connectivity supporting the suggested AG role in the integration of sensory input for modulating motor control and planning. The present description of AG’s highly distributed wiring diagram may drastically improve intraoperative subcortical testing and post-operative neurologic outcomes related to surgery in and around the angular gyrus.

The temporo-parietal junction (TPJ) is a cortical area contributing to a multiplicity of visual, language-related and cognitive functions. In line with this functional richness, also the organization of the underlying white matter is highly complex and includes several bundles. The few studies tackling to date the outcome and neurological burdens of surgical operations addressing TPJ document the presence of language disturbances and visual field damages, with the latter hardly recovered in time. This observation advocates for procedures identifying the optic radiation (OR) bundles crossing the white matter (WM) below TPJ. In the present study we adopted a multimodal approach to address the anatomo-functional correlates of the dorsal loop (DL) of the OR. In particular, we combined cadavers’ dissection with tractographic and electrophysiological data collected in drug-resistant epileptic patients explored by stereoelectroencephalography (SEEG). Cadaver dissection allowed us to appreciate the position and geometrical properties of the DL. More surprisingly, both tractographic and electrophysiological observations converged on a unitary picture highly coherent with the data obtained by neuroanatomical observation.The combination of diverse and multimodal observations allows to overcome the limitations intrinsic to single methodologies, and to define a unitary picture which makes it possible to investigate DL presurgically and at the individual patient level, aiming at limiting the postsurgical damages. Notwithstanding, such a combined approach could serve as a model of investigation for future neuroanatomical inquiries tackling WM fibers anatomy and function through SEEG-derived neurophysiological data.

Purpose To evaluate the clinical outcomes, toxicity and prognostic factors conditioning survival of reirradiation with Proton therapy for recurrent meningiomas. Methods Recurrent meningioma who failed after radiotherapy were re-irradiated with active scanning proton therapy with a median dose of 54 GyRBE (range 50.4-60 GyRBE). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The log rank test was performed to compare the entire survival experience between groups (significant p-value ≤ 0.05). Associations between qualitative variables were analyzed with the Fisher exact test (significant p-value ≤ 0.05). Results Thirty-two patients were re-irradiated with Proton therapy (10 grade I, 22 grade II-III). Median tumor volume at the time of re-irradiation was 43 cc (range 1.2-225.5) and median time from prior RT to reirradiation was 66 months (range 4-288). At a median follow-up of 27 months, 1-yr and 2-yr PFS were 89.4% and 74.5% (1-yr and 2-yr PFS were 100% for grade I, 100% and 76% for grade II, 66% and 50% for grade III). 1-yr and 2-yr OS were 86.6% and 83.0% (2-yr OS were 87% for grade I, 86% for grade II, 66% for grade III). Local recurrence rate was 34% with a median time of recurrence of 13.4 months. Five patients (14%) developed radionecrosis with a median time of 3.4 months from the end of PT (range 3-8.8). Conclusions Re-irradiation with proton therapy seems to be a safe and effective treatment in patients with recurrent meningioma, also for large volume and aggressive lesions (grade II-III).

We constantly face situations involving interactions with others that require us to automatically adjust our physical distances to avoid discomfort or anxiety. A previous case study has demonstrated that the integrity of both amygdalae is essential to regulate interpersonal distances. Despite unilateral lesion to the amygdala, as to other sectors of the medial temporal cortex, are known to also affect social behavior, their role in the regulation of interpersonal distances has never been investigated. Here, we sought to fill this gap by testing three patients with unilateral temporal lesions following surgical resections, including one patient with a lesion mainly centered on the amygdala and two with lesions to adjacent medial temporal cortex, on two versions of the stop distance paradigm (i.e. in a virtual reality environment and in a real setting). Our results showed that all three patients set shorter interpersonal distances compared to neurotypical controls. In addition, compared to controls, none of the patients adjusted such physical distances depending on facial emotional expressions, despite they preserved ability to categorize them. Finally, patients' heart rate responses differed from controls when viewing approaching faces. Our findings bring compelling evidence that unilateral lesions within the medial temporal cortex, not necessarily restricted to the amygdala, are sufficient to alter interpersonal distance, thus shedding new light on the neural circuitry regulating distance in social interactions.

International audience; INTRODUCTION: Since its first description in the early 19 th century, the inferior frontooccipital fascicle (IFOF) and its anatomo-functional features were neglected in the neuroscientific literature for the last century. In the last decade, the rapid development of in vivo imaging for the reconstruction of white matter (WM) connectivity (i.e., tractography) and the consequent interest in more traditional ex vivo methods (postmortem dissection) have allowed a renewed debate about course, termination territories, anatomical relationships, and functional roles of this fascicle. EVIDENCE ACQUISITION: We reviewed the main current knowledge concerning the structural and functional anatomy of the IFOF and possible implications in neurosurgical practice. EVIDENCE SYNTHESIS: The IFOF connects the occipital cortex, the temporo-basal areas, the superior parietal lobule, and the pre-cuneus to the frontal lobe, passing through the ventral third of subinsular WM of the external capsule. This wide distribution of cortical terminations provides multimodal integration between several functional networks, including language, non-verbal semantic processing, object identification, visuo-spatial processing and planning, reading, facial expression recognition, memory and conceptualization, emotional and neuropsychological behavior. This anatomo-functional organization has important implication also in neurosurgical practice, especially when approaching the frontal, insular, temporo-parieto-occipital regions and the ventricular system. CONCLUSIONS: The IFOF is the most extensive associative bundle of the human connectome. Its multi-layer organization reflects important implications in many aspects of brain functional processing. Accurate awareness of IFOF functional anatomy and integration between multimodal datasets coming from different sources has crucial implications for both neuroscientific knowledge and quality of neurosurgical treatments.

The study of patients after glioma resection offers a unique opportunity to investigate brain reorganization. It is currently unknown how the whole-brain connectomic profile evolves longitudinally after surgical resection of a glioma and how this may be associated with tumor characteristics and cognitive outcome. In this longitudinal study, we investigate the impact of tumor lateralization and grade on functional connectivity (FC) in highly connected networks, or hubs, and cognitive performance. Twenty-eight patients (17 high-grade, 11 low-grade gliomas) underwent longitudinal pre/post-surgery resting-state fMRI scans and neuropsychological assessments (73 total measures). FC matrices were constructed considering as functional hubs the default mode (DMN) and fronto-parietal networks. No-hubs included primary sensory functional networks and any other no-hubs nodes. Both tumor hemisphere and grade affected brain reorganization post-resection. In right-hemisphere tumor patients, regardless of grade and relative to left-hemisphere gliomas, FC increased longitudinally after the intervention, both in terms of FC within hubs (phubs = 0.0004) and FC between hubs and no-hubs (phubs-no-hubs = 0.005). Regardless of tumor side, only lower-grade gliomas showed longitudinal FC increases relative to high-grade tumors within a precise hub network, the DMN. The neurocognitive profile was longitudinally associated with spatial features of the connectome, mainly within the DMN. We provide evidence that clinical glioma features, such as lateralization and grade, affect post-surgical longitudinal functional reorganization and cognitive recovery. The data suggest a possible role of the DMN in supporting cognition, providing useful information for prognostic prediction and surgical planning.

Purpose The practical management of cavernous angioma located within eloquent brain area before, during and after surgical resection is poorly documented. We assessed the practical pre-operative, intra-operative, and post-operative management of cavernous angioma located within eloquent brain area. Method An online survey composed of 61 items was sent to 26 centers to establish a multicenter international retrospective cohort of adult patients who underwent a surgical resection as the first-line treatment of a supratentorial cavernous angioma located within or close to eloquent brain area. Results 272 patients from 19 centers (mean 13.6 ± 16.7 per center) from eight countries were included. The pre-operative management varied significantly between centers and countries regarding the pre-operative functional assessment, the pre-operative epileptological assessment, the first given antiepileptic drug, and the time to surgery. The intra-operative environment varied significantly between centers and countries regarding the use of imaging systems, the use of functional mapping with direct electrostimulations, the extent of resection of the hemosiderin rim, the realization of a post-operative functional assessment, and the time to post-operative functional assessment. The present survey found a post-operative improvement, as compared to pre-operative evaluations, of the functional status, the ability to work, and the seizure control. Conclusions We observed a variety of practice between centers and countries regarding the management of cavernous angioma located within eloquent regions. Multicentric prospective studies are required to solve relevant questions regarding the management of cavernous angioma-related seizures, the timing of surgery, and the optimal extent of hemosiderin rim resection.

The aim of this Pictorial Essay is to illustrate the metabolic aspect of PET (positron emission tomography) imaging in relation to conventional and advanced MR (magnetic resonance) of brain neoplasms. 10 patients, who performed PET–CT with amino acid tracers and/or FDG were selected from a series of more than 250 cases from a single institution. The selection was made to illustrate and discuss each of the indications reported in the European guidelines. Fusion imaging was obtained merging PET–CT with MR T1-CE (contrast enhanced) and/or T2/FLAIR sequences. The SUVmax of the lesion and the SUVmax lesion to SUVmax background ratio were evaluated. The lesion uptake was also assessed using a five-point visual scale with a range from − 2 to + 2 in relation to basal ganglia uptake. The Hospital Information System (HIS) and the proton therapy data archives have been used for clinical history. For each case, the critical issues were described and the physiopathological correlations were provided to explain the imaging findings. The complexity of illustrated cases demonstrates the need for a multidisciplinary board evaluation to reach a more accurate diagnosis.

International audience; The description of human white matter pathways experienced a tremendous improvement thanks to the advancement of neuroimaging and dissection techniques. The downside of this progress is the production of redundant and conflicting literature, bound by specific studies’ methods and aims. The Superior Longitudinal System (SLS), encompassing the arcuate (AF) and the superior longitudinal fasciculi (SLF), becomes an illustrative example of this fundamental issue, being one of the most studied white matter association pathways of the brain. Herein we provide a complete illustration of this white matter fiber system’s current definition, from its early descriptions in the 19th century to its most recent characterizations. We propose a review of both in vivo diffusion magnetic resonance imaging-based tractography and anatomical dissection studies, enclosing all the information available up to date. Based on these findings, we reconstruct the wiring diagram of the SLS, highlighting a substantial variability in the description of its cortical sites of termination and the taxonomy and partonomy that characterize the system. We aim to level up discrepancies in the literature by proposing a parallel across the various nomenclature. Consistently with the topographical arrangement already documented for commissural and projection pathways, we suggest approaching the SLS organization as an orderly and continuous wiring diagram, respecting a medio-lateral palisading topography between the different frontal, parietal, occipital, and temporal gyri rather than in terms of individualized fascicles. A better and complete description of the fine organization of white matter association pathways’ connectivity is fundamental for a better understanding of brain function and their clinical and neurosurgical applications.

International audience; We appreciate the concerns of Drs. Maldonado, Smirnov, and Destrieux about our review article "Hodology of the superior longitudinal system of the human brain: a historical perspective, the current controversies, and a proposal" (Vavassori et al., 2021). We agree that we need further investigations on the white matter association systems' multilayer architecture, which we described as a palisading topographical arrangement, to benefit from more detailed descriptions of the cortical terminations.

The description of human white matter pathways experienced a tremendous improvement, thanks to the advancement of neuroimaging and dissection techniques. The downside of this progress is the production of redundant and conflicting literature, bound by specific studies' methods and aims. The Superior Longitudinal System (SLS), encompassing the arcuate (AF) and the superior longitudinal fasciculi (SLF), becomes an illustrative example of this fundamental issue, being one of the most studied white matter association pathways of the brain. Herein, we provide a complete illustration of this white matter fiber system's current definition, from its early descriptions in the nineteenth century to its most recent characterizations. We propose a review of both in vivo diffusion magnetic resonance imaging-based tractography and anatomical dissection studies, enclosing all the information available up to date. Based on these findings, we reconstruct the wiring diagram of the SLS, highlighting a substantial variability in the description of its cortical sites of termination and the taxonomy and partonomy that characterize the system. We aim to level up discrepancies in the literature by proposing a parallel across the various nomenclature. Consistent with the topographical arrangement already documented for commissural and projection pathways, we suggest approaching the SLS organization as an orderly and continuous wiring diagram, respecting a medio-lateral palisading topography between the different frontal, parietal, occipital, and temporal gyri rather than in terms of individualized fascicles. A better and complete description of the fine organization of white matter association pathways' connectivity is fundamental for a better understanding of brain function and their clinical and neurosurgical applications.

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called “virtual dissection.” Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. It is our opinion that if the field of dMRI tractography wants to be taken seriously as a widespread clinical tool, it is imperative to harmonize WM bundle segmentations and develop protocols aimed to be used in clinical settings. The EADC‐ADNI Harmonized Hippocampal Protocol achieved such standardization through a series of steps that must be reproduced for every WM bundle. This article is an observation of the problematic. A specific bundle segmentation protocol was used in order to provide a real‐life example, but the contribution of this article is to discuss the need for reproducibility and standardized protocol, as for any measurement tool. This study required the participation of 11 experts and 13 nonexperts in neuroanatomy and “virtual dissection” across various laboratories and hospitals. Intra‐rater agreement (Dice score) was approximately 0.77, while inter‐rater was approximately 0.65. The protocol provided to participants was not necessarily optimal, but its design mimics, in essence, what will be required in future protocols. Reporting tractometry results such as average fractional anisotropy, volume or streamline count of a particular bundle without a sufficient reproducibility score could make the analysis and interpretations more difficult. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction protocols in this era of open and collaborative science.

In 2018, the SINch (Italian Society of Neurosurgery) Neuro-Oncology Section, AINO (Italian Association of Neuro-Oncology) and SIN (Italian Association of Neurology) Neuro-Oncology Section formed a collaborative Task Force to look at the diagnosis and treatment of low-grade gliomas (LGGs). The Task Force included neurologists, neurosurgeons, neuro-oncologists, pathologists, radiologists, radiation oncologists, medical oncologists, a neuropsychologist and a methodologist. For operational purposes, the Task Force was divided into five Working Groups: diagnosis, surgical treatment, adjuvant treatments, supportive therapies, and follow-up. The resulting guidance document is based on the available evidence and provides recommendations on diagnosis and treatment of LGG patients, considering all aspects of patient care along their disease trajectory.

The aim of this work is to improve the virtual dissection of the Inferior Frontal Occipital Fasciculus (IFOF) by combining a recent insight on white matter anatomy from ex-vivo dissection and a data driven approach with a deep learning model. Current methods of tract dissection are not robust with respect to false positives and are neglecting the neuroanatomical waypoints of a given tract, like the stem. In this work we design a deep learning model to segment the stem of IFOF and we show how the dissection of the tract can be improved. The proposed method is validated on the Human Connectome Project dataset, where expert neuroanatomists segmented the IFOF on multiple subjects. In addition we compare the results to the most recent method in the literature for automatic tract dissection.

Disagreement exists regarding representational and connectionist interpretations of semantic knowledge subserved by the right versus left anterior temporal lobes (ATLs). These interpretations predict a different pattern of impairment in patients with a right unilateral ATL lesion. We conducted a neuropsychological study of a selective semantic pictorial defect exhibited by a 57-year-old man who had undergone a right temporal lobectomy due to the presence of a glioblastoma. The patient was given the Thematic and Taxonomic Semantic task, in which individuals must select, within triplets of words or pictures, the best associates of living or nonliving stimuli, related by thematic or taxonomic links, and presented in the verbal or pictorial modality. The selectivity of the defect was documented by a comparison between the results obtained by our patient and those obtained by healthy controls on living items and on pictures with a thematic relation. The selectivity of the defect was confirmed by a within-subject analysis of the results obtained on all of the task's triplets and those obtained on the stimuli representing living entities with a taxonomic relation. The selectivity of this semantic pictorial defect mainly concerning living entities is consistent with the representational account of semantic defects observed in our patient. In the present case report, a right temporal lobectomy resulted in a selective semantic pictorial defect with the qualitative features predicted by the representational account of semantic defects observed after a unilateral ATL lesion.

International audience; In this data article, we provide the dataset which served as the basis for our related research article "Mapping critical cortical hubs and white matter pathways by direct electrical stimulation: an original functional atlas of the human brain" [1], which represents the first probabilistic cortical and subcortical atlas of critical structures mediating human brain functions based on direct electrical stimulation (DES) in patients undergoing awake brain surgery. 1162 cortical and 659 subcortical DES-derived responses were recorded during testing of 16 functional domains in 256 patients undergoing awake surgery. Normalized [Montreal Neurological Institute (MNI) 152] spatial coordinates for cortical and subcortical responses, and probabilistic heat maps for each functional domain, were computed using methods previously developed by our group [2,3]. Source data, including the MNI-normalized coordinates of all 1821 DES-derived cortical and subcortical data points, and multi-planar (MNI-152, T1 1mm) videos showing the probabilistic distribution of each functional domain are provided. This novel dataset can improve and refine our understanding about the functional anatomy of critical brain networks, and these data are made available for medical and neuroscience applications.

Virtual delineation of white matter bundles in the human brain is of paramount importance for multiple applications, such as pre-surgical planning and connectomics. A substantial body of literature is related to methods that automatically segment bundles from diffusion Magnetic Resonance Imaging (dMRI) data indirectly, by exploiting either the idea of connectivity between regions or the geometry of fiber paths obtained with tractography techniques, or, directly, through the information in volumetric data. Despite the remarkable improvement in automatic segmentation methods over the years, their segmentation quality is not yet satisfactory, especially when dealing with datasets with very diverse characteristics, such as different tracking methods, bundle sizes or data quality. In this work, we propose a novel, supervised streamline-based segmentation method, called Classifyber, which combines information from atlases, connectivity patterns, and the geometry of fiber paths into a simple linear model. With a wide range of experiments on multiple datasets that span from research to clinical domains, we show that Classifyber substantially improves the quality of segmentation as compared to other state-of-the-art methods and, more importantly, that it is robust across very diverse settings. We provide an implementation of the proposed method as open source code, as well as web service.

Purpose: Awake surgery is an established technique for resection of low-grade gliomas, while its possible benefit for resection of high-grade gliomas (HGGs) needs further confirmations. This retrospective study aims to compare overall survival, extent of resection(EOR) and cognitive outcome in two groups of HGGs patients submitted to asleep or awake surgery. Methods: Thirty-three patients submitted to Gross Total Resection of contrast-enhancing area of HGGs were divided in two homogeneous groups: awake (AWg; N = 16) and asleep surgery (ASg; N = 17). All patients underwent toan extensive neuropsychological assessment before surgery (time_1), 1-week (time_2) and 4-months (time_3) after surgery. We performed analyses to assess differences in cognitive performances between groups, cognitive outcomes in each group and EOR. A comparison of overallsurvival(OS) between the twogroups was conducted. Results: Statisticalanalyses showed no differences between groups at time_2 and time_3 in each cognitive domain, excludingselective attentionthat resulted higher in the AWg before surgery. Regarding cognitive outcomes, we found a reversible worsening of memory and constructional praxis, and a significant recovery at time_3, similar for both groups. Assessment of time_3 in respect to time_1 never showed differences (all ps >.074). Moreover we found a significant lower level of tumor infiltration after surgery for AWg (p

International audience; 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.

International audience; BACKGROUND:Advances in the oncologic and functional results of insular surgery have been reported recently. Such successes have been made possible by the advent of the transopercular approach under awake monitoring and by improved anatomic and functional knowledge of white matter pathways surrounding the insula. Nonetheless, given the rarity of insular tumors, it is difficult to get familiar with the complex 3-dimensional anatomy of the different neuronal and vascular structures encountered during a transopercular insular resection. We thus propose to develop a laboratory model allowing to train transopercular approaches of the insula.METHODS:Two hemispheres prepared with Klinger's technique were dissected under light microscope, preserving all pial membranes. The different steps of the dissection were video recorded.RESULTS:Preservation of pial membranes enabled us to simulate subpial resection, both during operculum removal and during insular cortex resection. The medial wall of the resection was defined by the inferior-fronto-occipital fasciculus, protecting from the lenticulostriate arteries.CONCLUSION:In this paper, we show that Klinger dissection with preservation of pial membranes provides a realistic model of insular surgery, allowing surgeons to learn and train on this highly specialized surgery.

Background High-grade gliomas are the most frequently occurring brain tumors and carry unfavorable prognosis. Literature is controversial regarding the effects of surgery on cognitive functions. Methods We analyzed a homogenous population of 30 patients with high-grade glioma who underwent complete resection. Patients underwent extensive neuropsychological analysis before surgery, 7 days after surgery, and approximately 40 days after surgery, before adjuvant treatments. Thirty-four neuropsychological tests were administered in the language, memory, attention, executive functions, and praxis domains. Results The preoperative percentage of patients with impairment in the considered tests ranged from 0% to 53.3% (mean 20.9%). Despite a general worsening at early follow-up, a significant recovery was observed at late follow-up. Preoperative performances in language and verbal memory tasks depended on the joint effect of tumor volume, volume of surrounding edema, and tumor localization, with major deficits in patients with left lateralized tumor, especially insular and temporal. Preoperative performances in attention and constructive abilities tasks depended on the joint effect of tumor volume, volume of surrounding edema, and patient age, with major deficits in patients ≥ 65 years old. Recovery at late follow-up depended on the volume of resected tumor, edema resorption, and patient age. Conclusions Longitudinal neuropsychological performance of patients affected by high-grade glioma depends, among other factors, on the complex interplay of tumor volume, volume of surrounding edema, tumor localization, and patient age. Reported results support the definition of criteria for surgical indication based on the above factors. They may be used to propose more customized surgical, oncological, and rehabilitative strategies.

Diffuse low-grade glioma form a rare entity affecting young people. Despite advances in surgery, chemotherapy, and radiation therapy, diffuse low-grade glioma are still incurable. According to current guidelines, maximum safe resection, when feasible, is the first line of treatment. Apart from surgery, all other treatment modalities (temozolomide, procarbazine-CCNU-vincristine regimen, and radiation therapy) are handled very differently among different teams, and this in spite of recent results of several phase 3 studies. Based on a European survey, this paper aimed to get a picture of this heterogeneity in diffuse low-grade glioma management, to identify clinically relevant questions raised by this heterogeneity of practice, and to propose new methodological frameworks to address these questions.

International audience; We thank Panesar and Fernandez-Miranda (2019) for their interest in our work (Mandonnet et al., 2018). However, based on their comments, there seems to be some misunderstanding. We should have more elaborated on the principles that grounded our classification. We aim at rationalizing the current terminology that everyone shares but which is anything but clear. To this end, we proposed a first principle, namely the taxonomic scheme. This way of organizing knowledge has been demonstrated to be very powerful in many areas of biological sciences. It allows to define at the same time broad categories (which we called "systems"), together with subcategories (which we called "tracts"). It allows the classification to be continuously revised as our knowledge of the exact trajectories of the connections becomes more and more accurate. We agree that numbering the different entities of a system by roman letters is not very informative (although please note that the numbering follows the anatomical orientation, from medial to lateral). However, this is the only way to make it easy to implement new knowledge. On the contrary, the anatomically-oriented attributes "dorsal" and "ventral" that are proposed by the authors are too restrictive consider for example the four subcomponents of the arcuate fasciculus described by the authors of the commentary (Fernández-Miranda et al., 2014). With this general principle in mind, it seems clear that the arcuate fasciculus belong to the broad category of "superior longitudinal system," as the central part of its trajectory (called the "stem, " in which all fibers converge before diverging again toward their destination) is in close relationship with the stems of the three superior longitudinal fasciculus. And we fully agree that the terminology "superior longitudinal fasciculus" should not be used for the arcuate fasciculus, as the whole shape of the tract is not longitudinal. Regarding the comment about the cingulum, we do not really understand the criticism, as we fully concur with their statement. We were among the first to deny the existence of the SLF I as initially described by Makris (Makris et al., 2005; Maldonado et al., 2012), and we also agree, as explained in the paper, to assign to the mesial longitudinal system the fronto-parietal fibers located mesially to the corona radiata. However, in our view, the most dorsal and medial fibers of the SLF

BACKGROUND: The postoperative outcomes and the predictors of seizure control are poorly studied for supratentorial cavernous angiomas (CA) within or close to the eloquent brain area. OBJECTIVE: To assess the predictors of preoperative seizure control, postoperative seizure control, and postoperative ability to work, and the safety of the surgery. METHODS: Multicenter international retrospective cohort analysis of adult patients benefitting from a functional-based surgical resection with intraoperative functional brain mapping for a supratentorial CA within or close to eloquent brain areas. RESULTS: A total of 109 patients (66.1% women; mean age 38.4 ± 12.5 yr), were studied. Age >38 yr (odds ratio [OR], 7.33; 95% confidence interval [CI], 1.53-35.19; P =. 013) and time to surgery > 12 mo (OR, 18.21; 95% CI, 1.11-296.55; P =. 042) are independent predictors of uncontrolled seizures at the time of surgery. Focal deficit (OR, 10.25; 95% CI, 3.16-33.28; P

International audience; Editorial on the Research Topic Organization of the White Matter Anatomy in the Human Brain Between nineteenth and twentieth centuries, neurosciences experienced the first sharing of experiences and competences between the world of brain anatomy and clinics. The improvements in the knowledge of human white matter (WM) anatomy provided the natural background to the structural definition of a wide spectrum of clinical syndromes. This "disconnection" experience was the first field of strict integration between the WM anatomical and clinical skills, and constituted the hard core for the development of the modern neurosciences over the last century (Catani and ffytche, 2005). While the second half of twentieth century has seen the neurophysiology taking a front role in the definition of the physiological and physio-pathological processing of brain circuitries, the last decade has definitively brought neuroimaging into the world of neuroscience. The functional magnetic resonance imaging (fMRI) and diffusion-weighted MRI (DWI) tractography have successively opened a new era for a better understanding of functional and structural anatomy of the human brain (Le Bihan and Johansen-Berg, 2012; Smith et al., 2013). In particular, DWI-based tractography was the first tool allowing the exploration of human WM in vivo with an unprecedented level of details, and it shed a new light in the knowledge of the brain anatomy that became, finally, more accessible (Jeurissen et al., 2019). Beyond the technical aspects related to the continuous necessary improvement of this approach (Maier-Hein et al., 2017), tractography produced a conceptual revolution leading that the wiring diagram of brain connections regained a center scene of neuroscience research. Such a revolution was not only in research but also in the clinical and neurosurgical domains and opened the "connectome" era (Sporns, 2013). The fields of neuroanatomy, neuroimaging, neurophysiology and clinical researches are currently closer as never before. In fact, two decades of exploration of brain structure and functional processing with an unprecedented level of sensitivity opened new challenges. Among others, the research for a ground truth in structural anatomy is definitely the most impressive, especially considering the basic and conceptual consequences of that in assessing a reliable knowledge of brain processing, clinics and plasticity. This is what the vast majority of the articles in this Research Topic highlight by describing association WM pathways (Bao et al.; David et al.; Panesar et al.), cortico-striatal Cacciola et al. and cortico-thalamic (Maffei et al.; Roddy et al.; Sun et al.) projection pathways.

Primary brain tumors are notoriously hard to resect surgically. Due to their infiltrative nature, finding the optimal resection boundary without damaging healthy tissue can be challenging. One potential tool to help make this decision is diffusion-weighted magnetic resonance imaging (dMRI) tractography. dMRI exploits the diffusion of water molecule along axons to generate a 3D modelization of the white matter bundles in the brain. This feature is particularly useful to visualize how a tumor affects its surrounding white matter and plan a surgical path. This paper reviews the different ways in which dMRI can be used to improve brain tumor resection, its benefits and also its limitations. We expose surgical tools that can be paired with dMRI to improve its impact on surgical outcome, such as loading the 3D tractography in the neuronavigation system and direct electrical stimulation to validate the position of the white matter bundles of interest. We also review articles validating dMRI findings using other anatomical investigation techniques, such as postmortem dissections, manganese-enhanced MRI, electrophysiological stimulations, and phantom studies with known ground truth. We will be discussing the areas of the brain where dMRI performs well and where the future challenges are. We will conclude this review with suggestions and take home messages for neurosurgeons, tractographers, and vendors for advancing the field and on how to benefit from tractography's use in clinical practice.

Objective The structural and functional organization of brain networks subserving basic daily activities (i.e. language, visuo-spatial cognition, movement, semantics, etc.) are not completely understood to date. Here, we report the first probabilistic cortical and subcortical atlas of critical structures mediating human brain functions based on direct electrical stimulation (DES), a well-validated tool for the exploration of cerebral processing and for performing safe surgical interventions in eloquent areas. Methods We collected 1162 cortical and 659 subcortical DES responses during testing of 16 functional domains in 256 patients undergoing awake surgery. Spatial coordinates for each functional response were calculated, and probability distributions for the entire patient cohort were mapped onto a standardized three-dimensional brain template using a multinomial statistical analysis. In addition, matching analyses were performed against prior established anatomy-based cortical and white matter (WM) atlases. Results The probabilistic maps for each functional domain were provided. The topographical analysis demonstrated a wide spatial distribution of cortical functional responses, while subcortical responses were more restricted, localizing to known WM pathways. These DES-derived data showed reliable matching with existing cortical and WM atlases as well as recent neuroimaging and neurophysiological data. Conclusions We present the first integrated and comprehensive cortical-subcortical atlas of structures essential for humans’ neural functions based on highly-specific DES mapping during real-time neuropsychological testing. This novel atlas can serve as a complementary tool for neuroscientists, along with data obtained from other modalities, to improve and refine our understanding of the functional anatomy of critical brain networks.

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called "virtual dissection". Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. The contribution of this study is to provide the first large-scale, international, multi-center variability assessment of the "virtual dissection" of the pyramidal tract (PyT). Eleven (11) experts and thirteen (13) non-experts in neuroanatomy and "virtual dissection" were asked to perform 30 PyT segmentation and their results were compared using various voxel-wise and streamline-wise measures. Overall the voxel representation is always more reproducible 1. CC-BY-NC-ND 4.0 International license available under a not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made The copyright holder for this preprint (which was this version posted April 30, 2019. ; https://doi.org/10.1101/623892 doi: bioRxiv preprint than streamlines (≈70% and ≈35% overlap respectively) and distances between segmen-tations are also lower for voxel-wise than streamline-wise measures (≈3mm and ≈6mm respectively). This needs to be seriously considered before using tract-based measures (e.g. bundle volume versus streamline count) for an analysis. We show and argue that future bundle segmentation protocols need to be designed to be more robust to human subjectivity. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction techniques in this era of open and collaborative science.