Language-Eloquent White Matter Pathway Tractography and the Course of Language Function in Glioma Patients

Object: As various recent studies show, damage to white matter pathways leads to permanent functional deficits in a high percentage of patients. Particularly the subcortical language network is complex, and its visualization has a tremendous relevance for neurosurgeons. This pilot study aims to correlate language-eloquent white matter pathways with the course of language function after the resection of left-sided perisylvian gliomas.Methods: We included 10 patients who underwent resection of highly language-eloquent high- (9 pts) and low-grade gliomas (1 pts). We performed navigated repetitive transcranial magnetic stimulation (nrTMS)-based tractography via diffusion tensor imaging fiber trackings (DTI FT) preoperatively (PRE-1), postoperatively (POST-1), and at long-term follow up or tumor recurrence (PRE-2). We separately tracked the inferior fronto-occipital fascicle (IFOF), the frontal aslant tract (FAT), and the superior longitudinal (SLF), and arcuate fascicle (AF), and correlated the amount of visualized fibers to the patients' language function at each date.Results: The changes of nrTMS-based DTI FTs of single white matter pathways correlated with the according status of language function for any of the pathways in 80% of patients and in 19 of 30 (63%) single pathway comparisons between PRE-1 and POST-1. Between POST-1 and PRE-2 the nrTMS-based DTI FTs correlated with the status of language function for any of the pathways in all patients and in 24 of 30 (80%) single pathway comparisons. Single FT results correlated with the according status of language function at POST-1 in 60, 70, and 60% of cases, and with the according status of language function at PRE-2 in 60, 90, and 90% of cases for the tracking of the IFOF, FAT, and SLF/AF, respectively.Conclusion: By the present results we were able to show that nrTMS-based DTI FT of the IFOF, FAT, and SLF/AF mainly correlates with the according status of language function preoperatively, postoperatively, and at long-term follow up after the resection of left-sided perisylvian gliomas

Mapping Verb Retrieval With nTMS:The Role of Transitivity

Navigated Transcranial Magnetic Stimulation (nTMS) is used to understand the cortical organization of language in preparation for the surgical removal of a brain tumor. Action naming with finite verbs can be employed for that purpose, providing additional information to object naming. However, little research has focused on the properties of the verbs that are used in action naming tasks, such as their status as transitive (taking an object; e.g., to read) or intransitive (not taking an object; e.g., to wink). Previous neuroimaging data show higher activation for transitive compared to intransitive verbs in posterior perisylvian regions bilaterally. In the present study, we employed nTMS and production of finite verbs to investigate the cortical underpinnings of transitivity. Twenty neurologically healthy native speakers of German participated in the study. They underwent language mapping in both hemispheres with nTMS. The action naming task with finite verbs consisted of transitive (e.g., The man reads the book) and intransitive verbs (e.g., The woman winks) and was controlled for relevant psycholinguistic variables. Errors were classified in four different error categories (i.e., non-linguistic errors, grammatical errors, lexico-semantic errors and, errors at the sound level) and were analyzed quantitatively. We found more nTMS-positive points in the left hemisphere, particularly in the left parietal lobe for the production of transitive compared to intransitive verbs. These positive points most commonly corresponded to lexico-semantic errors. Our findings are in line with previous aphasia and neuroimaging studies, suggesting that a more widespread network is used for the production of verbs with a larger number of arguments (i.e., transitives). The higher number of lexico-semantic errors with transitive compared to intransitive verbs in the left parietal lobe supports previous claims for the role of left posterior areas in the retrieval of argument structure information

Interdisziplinäre Therapie von Hirnmetastasen

Bei Patientinnen mit einem metastasierten Mammakarzinom zeigt sich eine steigende Inzidenz zerebraler Metastasen bei Fortschritten in der systemischen Therapie. Bei Metastasen des zentralen Nervensystems (ZNS) ist in den meisten Fällen eine lokale Therapie indiziert. Eine operative Therapie kommt bei symptomatischen Metastasen, singulären Metastasen oder zur Gewinnung einer Histologie infrage. Eine Radiatio der ZNS-Metastasen sollte nach Möglichkeit stereotaktisch erfolgen. Bei multiplen Hirnmetastasen bzw. im Rezidiv kann eine Ganzhirnbestrahlung durchgeführt werden, die mit kognitiven Einschränkungen assoziiert sein kann. In Einzelfällen kann bei asymptomatischen Metastasen und Wechsel der systemischen Therapie eine lokale Behandlung aufgeschoben werden, insbesondere wenn eine stereotaktische Bestrahlung nicht möglich ist. Erste Studiendaten für Patientinnen mit Hirnmetastasen liegen vor, jedoch besteht großer Bedarf an klinischer und translationaler Forschung

Bihemispheric Navigated Transcranial Magnetic Stimulation Mapping for Action Naming Compared to Object Naming in Sentence Context

Preoperative language mapping with navigated transcranial magnetic stimulation (nTMS) is currently based on the disruption of performance during object naming. The resulting cortical language maps, however, lack accuracy when compared to intraoperative mapping. The question arises whether nTMS results can be improved, when another language task is considered, involving verb retrieval in sentence context. Twenty healthy German speakers were tested with object naming and a novel action naming task during nTMS language mapping. Error rates and categories in both hemispheres were compared. Action naming showed a significantly higher error rate than object naming in both hemispheres. Error category comparison revealed that this discrepancy stems from more lexico-semantic errors during action naming, indicating lexico-semantic retrieval of the verb being more affected than noun retrieval. In an area-wise comparison, higher error rates surfaced in multiple right-hemisphere areas, but only trends in the left ventral postcentral gyrus and middle superior temporal gyrus. Hesitation errors contributed significantly to the error count, but did not dull the mapping results. Inclusion of action naming coupled with a detailed error analysis may be favorable for nTMS mapping and ultimately improve accuracy in preoperative planning. Moreover, the results stress the recruitment of both left- and right-hemispheric areas during naming

Benefit of Action Naming Over Object Naming for Visualization of Subcortical Language Pathways in Navigated Transcranial Magnetic Stimulation-Based Diffusion Tensor Imaging-Fiber Tracking

Visualization of functionally significant subcortical white matter fibers is needed in neurosurgical procedures in order to avoid damage to the language network during resection. In an effort to achieve this, positive cortical points revealed during preoperative language mapping with navigated transcranial magnetic stimulation (nTMS) can be employed as regions of interest (ROIs) for diffusion tensor imaging (DTI) fiber tracking. However, the effect that the use of different language tasks has on nTMS mapping and subsequent DTI-fiber tracking remains unexplored. The visualization of ventral stream tracts with an assumed lexico-semantic role may especially benefit from ROIs delivered by the lexico-semantically demanding verb task, Action Naming. In a first step, bihemispheric nTMS language mapping was administered in 18 healthy participants using the standard task Object Naming and the novel task Action Naming to trigger verbs in a small sentence context. Cortical areas in which nTMS induced language errors were identified as language-positive cortical sites. In a second step, nTMS-based DTI-fiber tracking was conducted using solely these language-positive points as ROIs. The ability of the two tasks’ ROIs to visualize the dorsal tracts Arcuate Fascicle and Superior Longitudinal Fascicle, the ventral tracts Inferior Longitudinal Fascicle, Uncinate Fascicle, and Inferior Fronto-Occipital Fascicle, the speech-articulatory Cortico-Nuclear Tract, and interhemispheric commissural fibers was compared in both hemispheres. In the left hemisphere, ROIs of Action Naming led to a significantly higher fraction of overall visualized tracts, specifically in the ventral stream’s Inferior Fronto-Occipital and Inferior Longitudinal Fascicle. No difference was found between tracking with Action Naming vs. Object Naming seeds for dorsal stream tracts, neither for the speech-articulatory tract nor the inter-hemispheric connections. While the two tasks appeared equally demanding for phonological-articulatory processes, ROI seeding through the task Action Naming seemed to better visualize lexico-semantic tracts in the ventral stream. This distinction was not evident in the right hemisphere. However, the distribution of tracts exposed was, overall, mirrored relative to those in the left hemisphere network. In presurgical practice, mapping and tracking of language pathways may profit from these findings and should consider inclusion of the Action Naming task, particularly for lesions in ventral subcortical regions

Dual-Task nTMS Mapping to Visualize the Cortico-Subcortical Language Network and Capture Postoperative Outcome-A Patient Series in Neurosurgery

BACKGROUND: Perioperative assessment of language function in brain tumor patients commonly relies on administration of object naming during stimulation mapping. Ample research, however, points to the benefit of adding verb tasks to the testing paradigm in order to delineate and preserve postoperative language function more comprehensively. This research uses a case series approach to explore the feasibility and added value of a dual-task protocol that includes both a noun task (object naming) and a verb task (action naming) in perioperative delineation of language functions. MATERIALS AND METHODS: Seven neurosurgical cases underwent perioperative language assessment with both object and action naming. This entailed preoperative baseline testing, preoperative stimulation mapping with navigated Transcranial Magnetic Stimulation (nTMS) with subsequent white matter visualization, intraoperative mapping with Direct Electrical Stimulation (DES) in 4 cases, and postoperative imaging and examination of language change. RESULTS: We observed a divergent pattern of language organization and decline between cases who showed lesions close to the delineated language network and hence underwent DES mapping, and those that did not. The latter displayed no new impairment postoperatively consistent with an unharmed network for the neural circuits of both object and action naming. For the cases who underwent DES, on the other hand, a higher sensitivity was found for action naming over object naming. Firstly, action naming preferentially predicted the overall language state compared to aphasia batteries. Secondly, it more accurately predicted intraoperative positive language areas as revealed by DES. Thirdly, double dissociations between postoperatively unimpaired object naming and impaired action naming and vice versa indicate segregated skills and neural representation for noun versus verb processing, especially in the ventral stream. Overlaying postoperative imaging with object and action naming networks revealed that dual-task nTMS mapping can explain the drop in performance in those cases where the network appeared in proximity to the resection cavity. CONCLUSION: Using a dual-task protocol for visualization of cortical and subcortical language areas through nTMS mapping proved to be able to capture network-to-deficit relations in our case series. Ultimately, adding action naming to clinical nTMS and DES mapping may help prevent postoperative deficits of this seemingly segregated skill

Functional Reorganization of Cortical Language Function in Glioma Patients—A Preliminary Study

Background: Functional reorganization (FR) was shown in glioma patients by direct electrical stimulation (DES) during awake craniotomy. This option for repeated mapping is available in cases of tumor recurrence and after decision for a second surgery. Navigated repetitive transcranial magnetic stimulation (nrTMS) has shown a high correlation with results of DES during awake craniotomy for language-negative sites (LNS) and allows for a non-invasive evaluation of language function. This preliminary study aims to examine FR in glioma patients by nrTMS.Methods: A cohort of eighteen patients with left-sided perisylvian gliomas underwent preoperative nrTMS language mapping twice. The mean time between mappings was 17 ± 12 months. The cortex was separated into anterior and posterior language-eloquent regions. We defined a tumor area and an area without tumor (WOT). Error rates (ER = number of errors per number of stimulations) and hemispheric dominance ratios (HDR) were calculated as the quotient of the left- and right-sided ER.Results: In cases in which most language function was located near the tumor during the first mapping, we found significantly more LNS in the tumor area during the second mapping as compared to cases in which function was not located near the tumor (p = 0.049). Patients with seizures showed fewer LNS during the second mapping. We found more changes of cortical language function in patients with a follow-up time of more than 13 months and lower WHO-graded tumors.Conclusion: Present results confirm that nrTMS can show FR of LNS in glioma patients. Its extent, clinical impact and correlation with DES requires further evaluation but could have a considerable impact in neuro-oncology

Neuronavigated repetitive transcranial magnetic stimulation as novel mapping technique provides insights into language function in primary progressive aphasia

Navigated repetitive transcranial magnetic stimulation (nrTMS) is an innovative technique that provides insight into language function with high accuracy in time and space. So far, nrTMS has mainly been applied in presurgical language mapping of patients with intracranial neoplasms. For the present study, nrTMS was used for language mapping in primary progressive aphasia (PPA). Seven patients (median age: 70 years, 4 males) with the non-fluent variant of PPA (nfvPPA) were included in this pilot study. Trains of nrTMS (5 Hz, 100% resting motor threshold) caused virtual lesions at 46 standardized cortical stimulation targets per hemisphere. Patients’ errors in a naming task during stimulation were counted. The majority of errors induced occurred during frontal lobe stimulation (34.3%). Timing errors and non-responses were most frequent. More errors were induced in the right hemisphere (58%) than in the left hemisphere (42%). Mapping was tolerated by all patients, however, discomfort or pain was reported for stimulation of frontal areas. The elevated right-hemispheric error rate in our study could be due to a partial shift of language function to the right hemisphere in neurodegenerative aphasia during the course of disease and therefore points to the existence of neuronal plasticity in nfvPPA. While this is an interesting finding for neurodegenerative disorders per se, its promotion might also harbor future therapeutic targets

Motor Cortical Network Plasticity in Patients With Recurrent Brain Tumors

Objective: The adult brain’s potential for plastic reorganization is an important mechanism for the preservation and restoration of function in patients with primary glial neoplasm. Patients with recurrent brain tumors requiring multiple interventions over time present an opportunity to examine brain reorganization. Magnetoencephalography (MEG) is a noninvasive imaging modality that can be used for motor cortical network mapping which, when performed at regular intervals, offers insight into this process of reorganization. Utilizing MEG-based motor mapping, we sought to characterize the reorganization of motor cortical networks over time in a cohort of 78 patients with recurrent glioma. Methods: MEG-based motor cortical maps were obtained by measuring event-related desynchronization (ERD) in ß-band frequency during unilateral index finger flexion. Each patient presented at our Department at least on two occasions for tumor resection due to tumor recurrence, and MEG-based motor mapping was performed as part of preoperative assessment before each surgical resection. Whole-brain activation patterns from first to second MEG scan (obtained before first and second surgery) were compared. Additionally, we calculated distances of activation peaks, which represent the location of the primary motor cortex (MC), to determine the magnitude of movement in motor eloquent areas between the first and second MEG scan. We also explored which demographic, anatomic, and pathological factors influence these shifts. Results: The whole-brain activation motor maps showed a subtle movement of the primary MC from first to second timepoint, as was confirmed by the determination of motor activation peaks. The shift of ipsilesional MC was directly correlated with a frontal-parietal tumor location (p < 0.001), presence of motor deficits (p = 0.021), and with a longer period between MEG scans (p = 0.048). Also, a disengagement of wide areas in the contralesional (ipsilateral to finger movement) hemisphere at the second time point was observed. Conclusions: MEG imaging is a sensitive method for depicting the plasticity of the motor cortical network. Although the location of the primary MC undergoes only subtle changes, appreciable shifts can occur in the setting of a stronger and longer impairment of the tumor on the MC. The ipsilateral hemisphere may serve as a reservoir for functional recovery