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.

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.

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.

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.

New insights into the anatomo-functional architecture of the right sagittal stratum and its surrounding pathways: an axonal electrostimulation mapping study.

The sagittal stratum (SS) is a large sheet-like structure where major axonal fiber tracts cross, though its anatomical delineations are still debated. Here we investigated the poorly studied anatomo-functional organization of the right SS using direct electrical stimulation (DES) in patients undergoing wide-awake surgery for a cerebral glioma. Seventeen patients were included. There were six males, the mean age was 38 years old. One patient underwent surgery twice. Fourteen patients were right-handed and one was ambidextrous. Behavior tasks were used to monitor online the patients' functions during DES, including visual and somesthetic processes, semantics, language, spatial and social cognition. Beyond the cortical DES, the mapping of axonal pathways evoked various functional responses. At the level of the core of the right SS, there were visual disturbances, visual hemi-agnosia, semantic paraphasia, left spatial neglect, confusion and comprehension difficulties, anomia, and mentalizing disturbances. At the level of the surrounding axonal pathways, there were left spatial neglect, anomia, vertigo, dysesthesia, and hearing disturbances. Our functionally defined three-dimensional map indicates that this complex region has a multilayered functional architecture, and supports an organization founded on two anatomical systems: a core system formed by the optic radiations, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus, and a peripheral one composed of surrounding or intersecting white matter tracts, including the superior longitudinal fasciculus/arcuate fasciculus, thalamocortical radiations, auditory radiations, and parieto-insular vestibular system. These results should prompt neurosurgeons to achieve awake DES mapping within the right SS because of the likelihood of causing multiple and irreversible structural disconnections.

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

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

A probabilistic map of negative motor areas of the upper limb and face: a brain stimulation study.

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.

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.

Combining resting state functional MRI with intraoperative cortical stimulation to map the mentalizing network.

OBJECTIVE: To infer the face-based mentalizing network from resting-state functional MRI (rsfMRI) using a seed-based correlation analysis with regions of interest identified during intraoperative cortical electrostimulation. METHODS: We retrospectively included 23 patients in whom cortical electrostimulation induced transient face-based mentalizing impairment during 'awake' craniotomy for resection of a right-sided diffuse low-grade glioma. Positive stimulation sites were recorded and transferred to the patients' preoperative normalized MRI, and then used as seeds for subsequent seed-to-voxel functional connectivity analyses. The analyses, conducted with an uncorrected voxel-level p-value of 0.001 and a false-discovery-rate cluster-level p-value of 0.05, allowed identification of the cortical structures, functionally coupled with the mentalizing-related sites. RESULTS: Two clusters of responsive stimulations were identified intraoperatively - one in the right dorsolateral prefrontal cortex (dlPFC, n = 13) and the other in the right inferior frontal gyrus (IFG, n = 10). A whole group level analysis revealed that stimulation sites correlated mainly with voxels located in the pars triangularis of the IFG, the dorsolateral and dorsomedial prefrontal cortices, the temporo-parietal junction, the posterior superior temporal sulcus, and the posterior inferior temporal/fusiform gyrus. Other analyses, taking into consideration the location of the responsive sites (IFG versus dlPFC cluster), highlighted only minor differences between both groups. CONCLUSIONS: The present study successfully demonstrated the involvement of a large-scale neural network in the face-based mentalizing that strongly matches networks, classically identified using task-based fMRI paradigms. We thus validated the combination of rsfMRI and stimulation mapping as a powerful approach to identify functional networks in brain-damaged patients.

Electrical stimulation of the dorsolateral prefrontal cortex impairs semantic cognition.

OBJECTIVE: To identify the prefrontal cortical structures causally involved in verbal and nonverbal semantic cognition in both cerebral hemispheres. METHODS: We retrospectively screened the intraoperative brain mapping data of 584 patients who underwent neurosurgery for neoplastic tumor under local anesthesia with direct cortical electrostimulation. Patients were included if they were right-handed, recently diagnosed with a diffuse low-grade glioma, and had a positive language mapping for verbal (naming task) and nonverbal (visual semantic association task) semantic cognition in the prefrontal cortex (n = 49). Among these, 30 were tested intraoperatively with both the naming and the semantic association tasks, while 19 were tested with the naming task only. Subsequently, each semantic site (n = 85) was plotted individually onto a common stereotaxic space for detailed analyses. RESULTS: The cortical sites associated with verbal semantic disturbances (n = 45) were distributed in the pars opercularis (n = 14) and pars triangularis (n = 19) of the left inferior frontal gyrus, and left dorsolateral prefrontal cortex (dlPFC, n = 12); only 2 sites were observed in the right dlPFC. In contrast, all but one cortical site associated with nonverbal semantic disturbances were observed in the left dorsolateral cortex (n = 8). In the right hemisphere, the same disturbances were found in the dlPFC (n = 14) and pars opercularis (n = 2). CONCLUSION: The present study demonstrated the critical role of the dlPFC in the semantic network, and indicated its specific and bilateral involvement in nonverbal semantic cognition in right-handers.

Awake Surgery for Gliomas within the Right Inferior Parietal Lobule: New Insights into the Functional Connectivity Gained from Stimulation Mapping and Surgical Implications.

OBJECTIVE: Little is known about the functional role of the white matter connections running within and around the right inferior parietal lobule (IPL). We used direct electrostimulation during awake surgery to investigate this connectivity and to avoid permanent deficit after resection for right IPL gliomas. METHODS: We reviewed patients who underwent awake mapping for a glioma involving the right IPL. Resection was achieved up to functional corticosubcortical boundaries detected by electrostimulation. Results of the intraoperative mapping were confronted to preoperative and postoperative magnetic resonance imaging to perform anatomofunctional correlations. RESULTS: Fourteen consecutive patients were enrolled (9 men; mean age, 44 years). Cortically, the resection was limited anteriorly by the retrocentral somatosensory area (11 patients) or by the precentral motor cortex (3 patients). Subcortically, the thalamocortical pathways were identified anteriorly in all patients. Articulatory disturbances were elicited anteriorly and laterally (6 patients) corresponding to the superior longitudinal fasciculus part III. Deeper and superiorly, stimulating the superior longitudinal fasciculus part II or the arcuate fasciculus induced spatial disorders (6 patients). More laterally and posteriorly, disrupting the inferior fronto-occipital fasciculus induced nonverbal semantic disorders (7 patients). Six patients had visual deficits while the optic radiations were stimulated. A total or subtotal resection was achieved in all patients but one. There were no permanent impairments, except an expected left superior quadrantanopia in 4 patients. CONCLUSIONS: This is the first surgical series focusing on right IPL gliomas. The complex functional connectivity detected within and around this region fully supports the use of intraoperative multimodal functional mapping for optimizing outcomes.

Left Spatial Neglect Evoked by Electrostimulation of the Right Inferior Fronto-occipital Fasciculus.

Left spatial neglect is a debilitating condition that may occur after lesion of many cortical territories in the right hemisphere. At the subcortical level, the second and third branches of the right superior longitudinal fasciculus has emerged as strong candidates in conveying information exchanges within the attention networks as their damage has been repeatedly associated to spatial neglect in neuromodulation and neuropsychological studies. Yet, a few cases of spatial neglect have also been observed after damage to the right inferior fronto-occipital fasciculus (IFOF), suggesting an involvement of this associative connectivity in spatial attention. Here we report three rare cases of patients having undergone a wide-awake craniotomy with direct electrostimulation for right temporal glioma. An intraoperative monitoring of spatial cognition was performed using a standard line bisection task. Responsive cortical sites were observed in the supramarginal gyrus and the posterior part of both the middle and superior temporal gyri. Critically, in all patients, significant rightward deviations were observed by the stimulation of the white matter deep in the temporal lobe, along the roof of the inferior horn of the lateral ventricle-a well-known anatomical landmark to identify the IFOF. Disconnection analyses confirmed the high probability of IFOF disconnection during neglect-related stimulations. Taken together, our findings provide support for a role of the right IFOF in spatial cognition. We discuss these results in the light of the newly discovered fronto-parietal connections of the IFOF and suggest that some subcomponents of this tract might be involved in between-system integration within the attention network.

Challenging the Myth of Right Nondominant Hemisphere: Lessons from Corticosubcortical Stimulation Mapping in Awake Surgery and Surgical Implications.

For many years, the right hemisphere (RH) was considered as nondominant, especially in right-handers. In neurosurgical practice, this dogma resulted in the selection of awake procedure with language mapping only for lesions of the left dominant hemisphere. Conversely, surgery under general anesthesia (possibly with motor mapping) was usually proposed for right lesions. However, when objective neuropsychological assessments were performed, they frequently showed cognitive and behavioral deficits after brain surgery, even in the RH. Therefore, to preserve an optimal quality of life, especially in patients with a long survival expectancy (as in low-grade gliomas), awake surgery with cortical and axonal electrostimulation mapping has recently been proposed for resection of right tumors. Here, we review new insights gained from intraoperative stimulation into the pivotal role of the RH in movement execution and control, visual processes and spatial cognition, language and nonverbal semantic processing, executive functions (e.g., attention), and social cognition (mentalizing and emotion recognition). These original findings, which break with the myth of a nondominant RH, may have important implications in cognitive neurosciences, by improving our knowledge of the functional connectivity of the RH, as well as for the clinical management of patients with a right lesion. In brain surgery, awake mapping should be considered more systematically in the RH. Moreover, neuropsychological examination must be achieved in a more systematic manner before and after surgery within the RH, to optimize care by predicting the likelihood of functional recovery and by elaborating specific programs of rehabilitation.

Direct evidence for the contributive role of the right inferior fronto-occipital fasciculus in non-verbal semantic cognition.

The neural foundations underlying semantic processing have been extensively investigated, highlighting a pivotal role of the ventral stream. However, although studies concerning the involvement of the left ventral route in verbal semantics are proficient, the potential implication of the right ventral pathway in non-verbal semantics has been to date unexplored. To gain insights on this matter, we used an intraoperative direct electrostimulation to map the structures mediating the non-verbal semantic system in the right hemisphere. Thirteen patients presenting with a right low-grade glioma located within or close to the ventral stream were included. During the 'awake' procedure, patients performed both a visual non-verbal semantic task and a verbal (control) task. At the cortical level, in the right hemisphere, we found non-verbal semantic-related sites (n = 7 in 6 patients) in structures commonly associated with verbal semantic processes in the left hemisphere, including the superior temporal gyrus, the pars triangularis, and the dorsolateral prefrontal cortex. At the subcortical level, we found non-verbal semantic-related sites in all but one patient (n = 15 sites in 12 patients). Importantly, all these responsive stimulation points were located on the spatial course of the right inferior fronto-occipital fasciculus (IFOF). These findings provide direct support for a critical role of the right IFOF in non-verbal semantic processing. Based upon these original data, and in connection with previous findings showing the involvement of the left IFOF in non-verbal semantic processing, we hypothesize the existence of a bilateral network underpinning the non-verbal semantic system, with a homotopic connectional architecture.

Right Cortical and Axonal Structures Eliciting Ocular Deviation During Electrical Stimulation Mapping in Awake Patients.

To investigate the neural network underpinning eye movements, a cortical and subcortical intraoperative mapping using direct electrical stimulation (DES) was achieved in six awake patients during surgery for a right frontal low-grade glioma. We assessed the relationship between the occurrence of ocular deviation during both cortical and axonal DES and the anatomic location for each response. The corresponding stimulation sites were reported on a standard brain template for visual analysis and between-subjects comparisons. Our results showed that DES of the cortical frontal eye field (FEF) elicited horizontal (anterior FEF) or upward (posterior FEF) eye movements in 3 patients, supporting the fact that FEF comprises several distinct functional subregions. In addition, subcortical stimulation of the white matter tracts underneath the FEF evoked conjugate contraversive ocular deviation in 3 other patients. Interestingly, this region seems to be a crossroad between the fronto-striatal tract, the frontal aslant tract, the inferior fronto-occipital fascicle and the superior longitudinal fascicle. No deficits in eye movements were observed following surgery. To our knowledge, this is the first study reporting ocular deviation during axonal electrostimulation mapping of the white matter fibers in awake patients. Therefore, our original data issued from DES give new insights into the cortical and subcortical structures involved in the control of eye movements and their strong relationships with other functional pathways.

Mapping neuroplastic potential in brain-damaged patients.

It is increasingly acknowledged that the brain is highly plastic. However, the anatomic factors governing the potential for neuroplasticity have hardly been investigated. To bridge this knowledge gap, we generated a probabilistic atlas of functional plasticity derived from both anatomic magnetic resonance imaging results and intraoperative mapping data on 231 patients having undergone surgery for diffuse, low-grade glioma. The atlas includes detailed level of confidence information and is supplemented with a series of comprehensive, connectivity-based cluster analyses. Our results show that cortical plasticity is generally high in the cortex (except in primary unimodal areas and in a small set of neural hubs) and rather low in connective tracts (especially associative and projection tracts). The atlas sheds new light on the topological organization of critical neural systems and may also be useful in predicting the likelihood of recovery (as a function of lesion topology) in various neuropathological conditions-a crucial factor in improving the care of brain-damaged patients.

Somatotopic organization of the white matter tracts underpinning motor control in humans: an electrical stimulation study.

The somatotopic organization of the primary motor cortex is well documented. However, a possible somatotopy of the network involved in motor control, i.e., eliciting negative motor phenomena during electrostimulation, is unknown in humans, particularly at the subcortical level. Here, we performed electrical stimulation mapping in awake patients operated for gliomas, to study the distribution of the white matter tracts subserving movement control of the lower limb, upper limb(s), and speech. Eighteen patients underwent awake surgery for frontal low-grade gliomas, by using intraoperative subcortical electrostimulation mapping to search interference with movement of the leg, arm(s), and face. We assessed the negative motor responses and their distribution throughout the tracts located under premotor areas. The corresponding stimulation sites were reported on a standard brain template for visual analysis and between-subjects comparisons. During stimulation of the white matter underneath the dorsal premotor cortex and supplementary motor area, rostral to the corticospinal tracts, all patients experienced cessation of the movement of lower and upper limbs, of bimanual coordination, and/or speech. These subcortical sites were somatotopically distributed. Indeed, stimulation of the fibers from mesial to lateral directions and from posterior to anterior directions evoked arrest of movement of the lower limb (mesially and posteriorly), upper limb(s), and face/speech (laterally and anteriorly). There were no postoperative permanent deficits. This is the first evidence of a somatotopic organization of the white matter bundles underpinning movement control in humans. A better knowledge of the distribution of this motor control network may be helpful in neurosciences and neurosurgery.

Role of the left frontal aslant tract in stuttering: a brain stimulation and tractographic study.

The neural correlates of stuttering are to date incompletely understood. Although the possible involvement of the basal ganglia, the cerebellum and certain parts of the cerebral cortex in this speech disorder has previously been reported, there are still not many studies investigating the role of white matter fibers in stuttering. Axonal stimulation during awake surgery provides a unique opportunity to study the functional role of structural connectivity. Here, our goal was to investigate the white matter tracts implicated in stuttering, by combining direct electrostimulation mapping and postoperative tractography imaging, with a special focus on the left frontal aslant tract. Eight patients with no preoperative stuttering underwent awake surgery for a left frontal low-grade glioma. Intraoperative cortical and axonal electrical mapping was used to interfere in speech processing and subsequently provoke stuttering. We further assessed the relationship between the subcortical sites leading to stuttering and the spatial course of the frontal aslant tract. All patients experienced intraoperative stuttering during axonal electrostimulation. On postsurgical tractographies, the subcortical distribution of stimulated sites matched the topographical position of the left frontal aslant tract. This white matter pathway was preserved during surgery, and no patients had postoperative stuttering. For the first time to our knowledge, by using direct axonal stimulation combined with postoperative tractography, we provide original data supporting a pivotal role of the left frontal aslant tract in stuttering. We propose that this speech disorder could be the result of a disconnection within a large-scale cortico-subcortical circuit subserving speech motor control.