Sylvie Moritz-Gasser

Is the left uncinate fasciculus essential for language? A cerebral stimulation study.

Despite a better understanding of the anatomy of the uncinate fasciculus (UF), its function remains poorly known. Our aim was to study the exact role of UF in language, and the possible existence of parallel distributed language networks within the “ventral stream”, underlaid by distinct subcortical tracts – namely the inferior occipito-temporal fasciculus (IOF) and UF.We report a series of 13 patients operated on awake for a glioma involving the left anterior temporal lobe or the orbitofrontal area. We used intraoperative electrostimulation, to perform accurate and reliable anatomofunctional correlations both at cortical and subcortical levels. Using postoperative MRI, we correlated these functional findings with the anatomical locations of the sites where language disturbances were elicited by stimulation.Intraoperative cortical stimulation found perilesional language sites in all cases. Subcortically, semantic paraphasia were induced in the 13 patients by stimulating the IOF, and phonological paraphasia were generated in 6 patients by stimulating the arcuate fasciculus. Interestingly, subcortical stimulation never elicited any language disturbances when performed at the level of the UF. Moreover, after a transient postoperative language deficit, all patients recovered, despite the removal of at least one part of the UF, as confirmed by control MRI.We suggest that UF is not systematically essential for language. It can be explained by the fact that the “semantic ventral stream” might be constituted by at least two parallel pathways, i. e. a direct pathway underlaid by the IOF, crucial for language semantics, and an indirect pathway subserved by UF, which can be functionally compensated. However, we have to underline the fact not all language functions can be probed during surgery, and that more sensitive tasks have now to be added.

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 Brocas area. Anomia/paraphasia data demonstrated foci not only within classical Wernickes 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. Brocas area as speech output region) and provide a distributed framework for future studies of neural networks.

Functional outcome after language mapping for insular World Health Organization Grade II gliomas in the dominant hemisphere: experience with 24 patients

OBJECT Despite the report of recent experiences of insular surgery in the past decade, there has been no series specifically dedicated to studying functional outcome following resection of insular WHO Grade II gliomas involving the dominant hemisphere, in patients with no or only mild preoperative language deficit. In this article, the authors analyze the contribution of awake mapping for preservation of brain function, especially language, in a homogeneous series of 24 patients who underwent surgery for insular Grade II gliomas within the dominant insular lobe. METHODS Twenty-four patients underwent surgery for an insular Grade II glioma involving the dominant hemisphere (22 left, 2 right), revealed by seizures in all but 1 case. The preoperative neurological examination result was normal in 17 patients (71%), whereas 7 patients presented with language disorders detected using an accurate language assessment performed by a speech therapist. All surgeries were performed on awake patients utilizing intra-operative language mapping involving cortical and subcortical stimulation. RESULTS There were no intrasurgical complications or postsurgical sensorimotor deficits. Despite an immediate postoperative language worsening in 12 cases (50%), all patients recovered to a normal status within 3 months, and 6 cases even improved in comparison with their preoperative examination results. The 24 patients returned to normal social and professional lives. Moreover, the surgery had a favorable impact on epilepsy in all but 4 cases (83%). On control MR imaging, 62.5% of resections were total or subtotal. Three patients underwent a second or third awake surgery, with no additional deficit. All but 2 patients (92%) are alive after a mean follow-up of 3 years (range 3-133 months). CONCLUSIONS Although insular surgery was long believed to be too risky, the present results show that the rate of permanent deficit, especially dysphasia, following resection of Grade II gliomas involving the dominant insula has been dramatically reduced (none in this patient series), thanks to the systematic use of intraoperative awake mapping, even in cases of repeated operations. Furthermore, patient quality of life may be improved due to a decrease of epilepsy after surgery. Thus, the authors suggest systematically considering resection when an insular Grade II glioma is diagnosed after seizures in a patient with no or mild deficit, even a glioma invading the dominant hemisphere.

Toward a pluri-component, multimodal, and dynamic organization of the ventral semantic stream in humans: lessons from stimulation mapping in awake patients.

For many decades, neural basis underlying cognitive functions was conceived in a localizationist framework. Owing to the development of connectomics, an alternative hodotopical account was proposed, in which brain functions are sub-served by the interactions of large-scale distributed and parallel subnetworks (Catani, 2007; de Benedictis and Duffau, 2011). In this setting, the processing of visual information is divided in a dorsal stream dedicated to the analysis of the spatial position (“where”) and in a ventral stream specialized in object identification (“what”; Underleider and Haxby, 1994). By analogy, a dual-stream model for auditory language processing was suggested, with a dorsal stream involved in mapping sound to articulation and a ventral stream involved in mapping sound to meaning (Hickok and Poeppel, 2004). Nonetheless, the neural structures supporting the ventral route is still controversial. We have recently proposed a new model of language, in which the subcortical anatomical constraints have been incorporated (Duffau et al., 2013): beyond a well-recognized dorsal phonological/articulatory stream underlain by the superior longitudinal fascicle, the neuroanatomy subserving a parallel ventral stream involved in multimodal semantics was described. Here, our purpose is to detail the dynamic functional anatomy of this multi-component ventral route, constituted by direct and indirect pathways (explaining a possible compensation following brain injury) and implied in pluri-modal semantic processes—i.e., in verbal and non-verbal comprehension, control and noetic consciousness.

Does the left superior longitudinal fascicle subserve language semantics? A brain electrostimulation study

Recent diffusion tensor imaging (DTI) tractography studies indicate that the supramarginal gyrus (SMG) represents a relay between frontal and temporal language sites. Some authors postulate that pathways connecting SMG to the posterior temporal lobe, i.e., the posterior part of the superior longitudinal fascicle (SLF) subserve semantic aspects of language. However, DTI provides only anatomic but not functional data. Therefore, it is impossible to conclude. Interestingly, intra-operative electrical mapping of cortical and subcortical language structures during tumor surgery is recognized as a reliable technique in functional neuroanatomy research. We mapped the underlying white matter of the SMG, especially the SLF, in 11 patients who underwent awake surgery for a glioma involving the left inferior parietal lobule. Using direct electrostimulation, we investigated the exact role of the SLF in language. Our findings indicate that the white matter under the inferior parietal lobule is highly involved in the dorsal phonological system. First, the SMG, connected to the ventral premotor cortex by horizontal fibers of the SLF, subserves articulatory processing, as demonstrated by dysarthria elicited by stimulation. Second, long arcuate fibers, found deeper in the white matter, subserve phonological processing, as supported by phonemic paraphasia induced by electrostimulation. Third, the most important result is that no semantic disturbances were elicited by stimulating the SLF, including its posterior part. Furthermore, no semantic disorders occurred postoperatively. Subcortical brain mapping by direct electrical stimulation does not provide arguments for a possible role of the left SLF in language semantic processing.

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 patients 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 pathways 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.

Subcortical electrostimulation to identify network subserving motor control

Objectives: Recent anatomical–functional studies have transformed our understanding of cerebral motor control away from a hierarchical structure and toward parallel and interconnected specialized circuits. Subcortical electrical stimulation during awake surgery provides a unique opportunity to identify white matter tracts involved in motor control. For the first time, this study reports the findings on motor modulatory responses evoked by subcortical stimulation and investigates the cortico‐subcortical connectivity of cerebral motor control. Experimental design: Twenty‐one selected patients were operated while awake for frontal, insular, and parietal diffuse low‐grade gliomas. Subcortical electrostimulation mapping was used to search for interference with voluntary movements. The corresponding stimulation sites were localized on brain schemas using the anterior and posterior commissures method. Principal observations: Subcortical negative motor responses were evoked in 20/21 patients, whereas acceleration of voluntary movements and positive motor responses were observed in three and five patients, respectively. The majority of the stimulation sites were detected rostral of the corticospinal tract near the vertical anterior‐commissural line, and additional sites were seen in the frontal and parietal white matter. Conclusions: The diverse interferences with motor function resulting in inhibition and acceleration imply a modulatory influence of the detected fiber network. The subcortical stimulation sites were distributed veil‐like, anterior to the primary motor fibers, suggesting descending pathways originating from premotor areas known for negative motor response characteristics. Further stimulation sites in the parietal white matter as well as in the anterior arm of the internal capsule indicate a large‐scale fronto‐parietal motor control network. Hum Brain Mapp 34:3023–3030, 2013.

Is the Human Left Middle Longitudinal Fascicle Essential for Language? A Brain Electrostimulation Study

Human brain pathways required for language processing are poorly known. A new white matter tract in humans, the middle longitudinal fascicle, has recently been anatomically determined by diffusion tensor imaging and suggested to be essential for language. Our aim is to determine the importance of the middle longitudinal fascicle for language processing. This study is based on 8 patients with glioma resection at least involving the superior temporal gyrus of the left dominant hemisphere. Language is systematically examined pre‐ and postoperatively at 3 months. Intraoperative electrostimulation is used to map cortical and subcortical structures as functional boundaries of the glioma resection, including those essential for language processing. The resections are extensive (on average 62 ml, ranging from 21 to 111 ml) and include a large part of the middle longitudinal fascicle in all patients. Intraoperatively, no interference with picture naming is observed by electrostimulation of the middle longitudinal fascicle, while in all patients the inferior fronto‐occipital fascicle is identified by eliciting semantic paraphasia as functional boundary. Postoperatively, no new permanent language deficits are detected by systematic language examination. Therefore, we suggest that the middle longitudinal fascicle may participate but is not essential for language processing. Hum Brain Mapp, 2011.

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. Hum Brain Mapp 35:1587–1596, 2014.

Middle longitudinal fasciculus delineation within language pathways: A diffusion tensor imaging study in human

INTRODUCTION The existence in the human brain of the middle longitudinal fasciculus (MdLF), initially described in the macaque monkey, is supported by diffusion tensor imaging studies. In the present work, we aim (1) to confirm that this fascicle is found constantly in control subjects with the use of DTI techniques and (2) to delineate the MdLF from the other fiber bundles that constitute the language pathways. MATERIALS AND METHODS Tractography was realized in four right-handed healthy volunteers for the arcuate fascicle, uncinate fascicle, inferior fronto-occipital fascicle, inferior longitudinal fascicle and the middle longitudinal fascicle. The fiber tracts were characterized for their size, mean fractional anisotropy (FA), for their length, number of streamlines, and lateralization indices were calculated. RESULTS The MdLF is found constantly and it is clearly delineated from the other fascicles that constitute the language pathways, especially the ventral pathway. It runs within the superior temporal gyrus white matter from the temporal pole, then it extends caudally in the upper part of the sagittal stratum and the posterior part of the corona radiata, to reach the inferior parietal lobule (angular gyrus). We found a leftward asymmetry for all fiber tracts when considering the mean FA. DISCUSSION Using DTI methods, we confirm that the MdLF connects the angular gyrus and the superior temporal gyrus. On the basis of these findings, the role of the MdLF is discussed. CONCLUSION The middle longitudinal fasciculus, connects the angular gyrus and the superior temporal gyrus and its course can be systematically differenciated from those of other fascicles composing both ventral and dorsal routes (IFOF, IFL, AF and UF).