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

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

Intraoperative functional remapping unveils evolving patterns of cortical plasticity.

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

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

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

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

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

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

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

Mapping critical cortical hubs and white matter pathways by direct electrical stimulation: an original functional atlas of the human brain.

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.

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

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

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.

Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol.

BACKGROUND: The European Low-Grade Glioma network indicated a need to better understand common practices regarding the managing of diffuse low-grade gliomas. This area has experienced great advances in recent years. METHOD: A general survey on the managing of diffuse low-grade gliomas was answered by 21 centres in 11 European countries. Here we focused on specific questions regarding perioperative and intraoperative cognitive assessments. RESULTS: More centres referred to the same speech and language therapist and/or neuropsychologist across all assessments; a core of assessment tools was routinely used across centres; fluency tasks were commonly used in the perioperative stages, and object naming during surgery; tasks that tapped on attention, executive functions, visuospatial awareness, calculation and emotions were sparsely administered; preoperative assessments were performed 1 month or 1 week before surgery; timing for postoperative assessments varied; finally, more centres recommended early rehabilitation, whenever needed. CONCLUSIONS: There is an emerging trend towards following similar practices for the management of low-grade gliomas in Europe. Our results are descriptive and formalise current discussions in our group. Also, they contribute towards the development of a European assessment protocol.

Comparison between resting state fMRI networks and responsive cortical stimulations in glioma patients.

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.

New insights into the neural network mediating reading processes provided by cortico-subcortical electrical mapping.

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.

Probabilistic map of critical functional regions of the human cerebral cortex: Broca's area revisited.

The organization of basic functions of the human brain, particularly in the right hemisphere, remains poorly understood. Recent advances in functional neuroimaging have improved our understanding of cortical organization but do not allow for direct interrogation or determination of essential (versus participatory) cortical regions. Direct cortical stimulation represents a unique opportunity to provide novel insights into the functional distribution of critical epicentres. Direct cortical stimulation (bipolar, 60 Hz, 1-ms pulse) was performed in 165 consecutive patients undergoing awake mapping for resection of low-grade gliomas. Tasks included motor, sensory, counting, and picture naming. Stimulation sites eliciting positive (sensory/motor) or negative (speech arrest, dysarthria, anomia, phonological and semantic paraphasias) findings were recorded and mapped onto a standard Montreal Neurological Institute brain atlas. Montreal Neurological Institute-space functional data were subjected to cluster analysis algorithms (K-means, partition around medioids, hierarchical Ward) to elucidate crucial network epicentres. Sensorimotor function was observed in the pre/post-central gyri as expected. Articulation epicentres were also found within the pre/post-central gyri. However, speech arrest localized to ventral premotor cortex, not the classical Broca's area. Anomia/paraphasia data demonstrated foci not only within classical Wernicke's area but also within the middle and inferior frontal gyri. We report the first bilateral probabilistic map for crucial cortical epicentres of human brain functions in the right and left hemispheres, including sensory, motor, and language (speech, articulation, phonology and semantics). These data challenge classical theories of brain organization (e.g. Broca's area as speech output region) and provide a distributed framework for future studies of neural networks.

Inferring a dual-stream model of mentalizing from associative white matter fibres disconnection.

In the field of cognitive neuroscience, it is increasingly accepted that mentalizing is subserved by a complex frontotemporoparietal cortical network. Some researchers consider that this network can be divided into two distinct but interacting subsystems (the mirror system and the mentalizing system per se), which respectively process low-level, perceptive-based aspects and high-level, inference-based aspects of this sociocognitive function. However, evidence for this type of functional dissociation in a given neuropsychological population is currently lacking and the structural connectivities of the two mentalizing subnetworks have not been established. Here, we studied mentalizing in a large sample of patients (n = 93; 46 females; age range: 18-65 years) who had been resected for diffuse low-grade glioma-a rare tumour that migrates preferentially along associative white matter pathways. This neurological disorder constitutes an ideal pathophysiological model in which to study the functional anatomy of associative pathways. We mapped the location of each patient's resection cavity and residual lesion infiltration onto the Montreal Neurological Institute template brain and then performed multilevel lesion analyses (including conventional voxel-based lesion-symptom mapping and subtraction lesion analyses). Importantly, we estimated each associative pathway's degree of disconnection (i.e. the degree of lesion infiltration) and built specific hypotheses concerning the connective anatomy of the mentalizing subnetworks. As expected, we found that impairments in mentalizing were mainly related to the disruption of right frontoparietal connectivity. More specifically, low-level and high-level mentalizing accuracy were correlated with the degree of disconnection in the arcuate fasciculus and the cingulum, respectively. To the best of our knowledge, our findings constitute the first experimental data on the structural connectivity of the mentalizing network and suggest the existence of a dual-stream hodological system. Our results may lead to a better understanding of disorders that affect social cognition, especially in neuropathological conditions characterized by atypical/aberrant structural connectivity, such as autism spectrum disorders.

Limited plastic potential of the left ventral premotor cortex in speech articulation: evidence from intraoperative awake mapping in glioma patients.

OBJECTIVES: Despite previous lesional and functional neuroimaging studies, the actual role of the left ventral premotor cortex (vPMC), i.e., the lateral part of the precentral gyrus, is still poorly known. EXPERIMENTAL DESIGN: We report a series of eight patients with a glioma involving the left vPMC, who underwent awake surgery with intraoperative cortical and subcortical language mapping. The function of the vPMC, its subcortical connections, and its reorganization potential are investigated in the light of surgical findings and language outcome after resection. PRINCIPAL OBSERVATIONS: Electrostimulation of both the vPMC and subcortical white matter tract underneath the vPMC, that is, the anterior segment of the lateral part of the superior longitudinal fascicle (SLF), induced speech production disturbances with anarthria in all cases. Moreover, although some degrees of redistribution of the vPMC have been found in four patients, allowing its partial resection with no permanent speech disorders, this area was nonetheless still detected more medially in the precentral gyrus in the eight patients, despite its invasion by the glioma. Moreover, a direct connection of the vPMC with the SLF was preserved in all cases. CONCLUSIONS: Our original data suggest that the vPMC plays a crucial role in the speech production network and that its plastic potential is limited. We propose that this limitation is due to an anatomical constraint, namely the necessity for the left vPMC to remain connected to the lateral SLF. Beyond fundamental implications, such knowledge may have clinical applications, especially in surgery for tumors involving this cortico-subcortical circuit.

Disruption of bimanual movement by unilateral subcortical electrostimulation.

OBJECTIVES: Cortical areas involved in bimanual coordination have been regularly studied by functional neuroimaging and electroencephalography. However, the subcortical connectivity underlying this complex function has received less attention. Here, we used the technique of direct electrostimulation in awake patients who underwent surgery for brain glioma, with the goal to investigate the white matter pathways subserving bimanual coordination. EXPERIMENTAL DESIGN: Eight patients were operated under local anesthesia for a frontal low-grade glioma. Intraoperative subcortical electrostimulation mapping was used to search interference with bimanual coordination. The corresponding stimulation sites were reported on brain MRI. PRINCIPAL OBSERVATIONS: All patients presented a complete arrest of the movement of both hands during unilateral subcortical stimulation of the white matter underneath the dorsal premotor cortex and the posterior part of the supplementary motor area, rostrally to the corticospinal tract, until the caudate nucleus and the anterior arm of the internal capsule. No movement deficits, especially no disturbances of bimanual coordination, were observed 3 months after surgery. CONCLUSIONS: This is the first evidence of bilateral negative motor responses elicited by unilateral subcortical stimulation. Such findings support the existence of a bilateral cortico-subcortical network connecting the premotor cortices, basal ganglia, and spinal cord, involved in the control of bimanual coordination. A better understanding of this modulatory motor circuit may have important implications in fundamental neurosciences as well as in brain surgery.

The role of left inferior fronto-occipital fascicle in verbal perseveration: a brain electrostimulation mapping study.

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.

Parietal network underlying movement control: disturbances during subcortical electrostimulation.

Our understanding of brain movement control has changed over the last two decades. Recent findings in the monkey and in humans have led to a parallel and interconnected network. Nevertheless, little is known about these networks. Here, we present two cases of patients with a parietal low-grade glioma. They underwent surgery under local anesthesia with cortical and subcortical mapping. For patient 1, subcortical electrostimulation immediately posterior to thalamocortical fibers induced movement disorders, with an inhibition of leg and arm movements medially and, more laterally, an acceleration of arm movement. For patient 2, electrostimulation of white matter immediately posterior to thalamocortical fibers induced an inhibition of both arm movement. It means that the detected fibers in the parietal lobe may be involved in the motor control modulation. They are distributed veil-like immediately posterior to thalamocortical pathways and could correspond to a fronto-parietal movement control subnetwork. These two cases highlight the major role of the subcortical connectivity in movement regulation, involving parietal lobe, thus the necessity to be identified and preserved during brain surgery.

The persistent crucial role of the left hemisphere for language in left-handers with a left low grade glioma: a stimulation mapping study.

BACKGROUND: Left-handers have a more bilateral language representation than right-handers. Therefore, in left-handers with a low-grade glioma (LGG) in the left hemisphere (LH), one could hypothesize that the right hemisphere (RH) might allow language compensation, at least partly, with no or only a minor persistent role of the LH in speech. However, although LGG induces language reorganization in right-handed patients, little is known in left-handers. Here, we report the first series of left-handers who underwent awake surgery for a left LGG using intraoperative mapping, in order to investigate whether there was still an involvement of LH in language. METHOD: Ten consecutive left-handed patients were operated for a left LGG (three frontal, four paralimbic, one parietal, one temporal, one parieto-temporal tumor) using an awake procedure with intraoperative electrical language mapping. RESULTS: Intraoperative language disorders were elicited in all cases but one by electrostimulation in the LH. Cortical language sites were detected in nine cases. Subcortical stimulation also demonstrated the crucial role of left white matter pathways in language, including the inferior occipital-frontal fascicle, arcuate fascicle, lateral segment of the superior longitudinal fascicle and fibers from the ventral premotor cortex. Moreover, stimulation of deep gray nuclei generated language disturbances in four patients. These nine patients experienced transient postoperative language worsening, supporting the persistent critical role of LH in speech. In only one patient, no language deficit was evoked intraoperatively and postoperatively. The ten patients returned to a normal life. Total or subtotal resection was achieved in all cases but one. CONCLUSIONS: Our results suggest that, even though the RH may participate in language compensation, the LH in left-handers still plays a crucial role, despite a left slow-growing LGG. Thus, we propose to routinely consider awake surgery for left LGG removal in left-handers patients, to optimize the extent of resection while preserving language.

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

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