Motor mapping of the hand muscles using peripheral innervation-based navigated transcranial magnetic stimulation to identify functional reorganization of primary motor regions in malignant tumors.

Tumor-related motor reorganization remains unclear. Navigated transcranial magnetic stimulation (nTMS) can investigate plasticity non-invasively. nTMS-induced motor-evoked potentials (MEPs) of different muscles are commonly used to measure the center of gravity (CoG), the location with the highest density of corticospinal neurons in the precentral gyrus. We hypothesized that a peripheral innervation-based MEP analysis could outline the tumor-induced motor reorganization with a higher clinical and oncological relevance. Then, 21 patients harboring tumors inside the left corticospinal tract (CST) or precentral gyrus were enrolled in group one (G1), and 24 patients with tumors outside the left CST or precentral gyrus were enrolled in Group 2 (G2). Median- and ulnar-nerve-based MEP analysis combined with diffusion tensor imaging fiber tracking was used to explore motor function distribution. There was no significant difference in CoGs or size of motor regions and underlying tracts between G1 and G2. However, G1 involved a sparser distribution of motor regions and more motor-positive sites in the supramarginal gyrus-tumors inside motor areas induced motor reorganization. We propose an "anchor-and-ship theory" hypothesis for this process of motor reorganization: motor CoGs are stably located in the cortical projection area of the CST, like a seated anchor, as the core area for motor output. Primary motor regions can relocate to nearby gyri via synaptic plasticity and association fibers, like a ship moving around its anchor. This principle can anticipate functional reorganization and be used as a neuro-oncological tool for local therapy, such as radiotherapy or surgery.

Comparing navigated transcranial magnetic stimulation mapping and "gold standard" direct cortical stimulation mapping in neurosurgery: a systematic review.

The objective of this systematic review is to create an overview of the literature on the comparison of navigated transcranial magnetic stimulation (nTMS) as a mapping tool to the current gold standard, which is (intraoperative) direct cortical stimulation (DCS) mapping. A search in the databases of PubMed, EMBASE, and Web of Science was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and recommendations were used. Thirty-five publications were included in the review, describing a total of 552 patients. All studies concerned either mapping of motor or language function. No comparative data for nTMS and DCS for other neurological functions were found. For motor mapping, the distances between the cortical representation of the different muscle groups identified by nTMS and DCS varied between 2 and 16 mm. Regarding mapping of language function, solely an object naming task was performed in the comparative studies on nTMS and DCS. Sensitivity and specificity ranged from 10 to 100% and 13.3-98%, respectively, when nTMS language mapping was compared with DCS mapping. The positive predictive value (PPV) and negative predictive value (NPV) ranged from 17 to 75% and 57-100% respectively. The available evidence for nTMS as a mapping modality for motor and language function is discussed.

Augmented reality for the virtual dissection of white matter pathways.

BACKGROUND: The human white matter pathway network is complex and of critical importance for functionality. Thus, learning and understanding white matter tract anatomy is important for the training of neuroscientists and neurosurgeons. The study aims to test and evaluate a new method for fiber dissection using augmented reality (AR) in a group which is experienced in cadaver white matter dissection courses and in vivo tractography. METHODS: Fifteen neurosurgeons, neurolinguists, and neuroscientists participated in this questionnaire-based study. We presented five cases of patients with left-sided perisylvian gliomas who underwent awake craniotomy. Diffusion tensor imaging fiber tracking (DTI FT) was performed and the language-related networks were visualized separated in different tracts by color. Participants were able to virtually dissect the prepared DTI FTs using a spatial computer and AR goggles. The application was evaluated through a questionnaire with answers from 0 (minimum) to 10 (maximum). RESULTS: Participants rated the overall experience of AR fiber dissection with a median of 8 points (mean ± standard deviation 8.5 ± 1.4). Usefulness for fiber dissection courses and education in general was rated with 8 (8.3 ± 1.4) and 8 (8.1 ± 1.5) points, respectively. Educational value was expected to be high for several target audiences (student: median 9, 8.6 ± 1.4; resident: 9, 8.5 ± 1.8; surgeon: 9, 8.2 ± 2.4; scientist: 8.5, 8.0 ± 2.4). Even clinical application of AR fiber dissection was expected to be of value with a median of 7 points (7.0 ± 2.5). CONCLUSION: The present evaluation of this first application of AR for fiber dissection shows a throughout positive evaluation for educational purposes.

The verb and noun test for peri-operative testing (VAN-POP): standardized language tests for navigated transcranial magnetic stimulation and direct electrical stimulation.

BACKGROUND: Protocols for intraoperative language mapping with direct electrical stimulation (DES) often include various language tasks triggering both nouns and verbs in sentences. Such protocols are not readily available for navigated transcranial magnetic stimulation (nTMS), where only single word object naming is generally used. Here, we present the development, norming, and standardization of the verb and noun test for peri-operative testing (VAN-POP) that measures language skills more extensively. METHODS: The VAN-POP tests noun and verb retrieval in sentence context. Items are marked and balanced for several linguistic factors known to influence word retrieval. The VAN-POP was administered in English, German, and Dutch under conditions that are used for nTMS and DES paradigms. For each language, 30 speakers were tested. RESULTS: At least 50 items per task per language were named fluently and reached a high naming agreement. CONCLUSION: The protocol proved to be suitable for pre- and intraoperative language mapping with nTMS and DES.

CompreTAP: Feasibility and reliability of a new language comprehension mapping task via preoperative navigated transcranial magnetic stimulation.

OBJECTIVE: Stimulation-based language mapping approaches that are used pre- and intraoperatively employ predominantly overt language tasks requiring sufficient language production abilities. Yet, these production-based setups are often not feasible in brain tumor patients with severe expressive aphasia. This pilot study evaluated the feasibility and reliability of a newly developed language comprehension task with preoperative navigated transcranial magnetic stimulation (nTMS). METHODS: Fifteen healthy subjects and six brain tumor patients with severe expressive aphasia unable to perform classic overt naming tasks underwent preoperative nTMS language mapping based on an auditory single-word Comprehension TAsk for Perioperative mapping (CompreTAP). Comprehension was probed by button-press responses to auditory stimuli, hence not requiring overt language responses. Positive comprehension areas were identified when stimulation elicited an incorrect or delayed button press. Error categories, case-wise cortical error rate distribution and inter-rater reliability between two experienced specialists were examined. RESULTS: Overall, the new setup showed to be feasible. Comprehension-disruptions induced by nTMS manifested in no responses, delayed or hesitant responses, searching behavior or selection of wrong target items across all patients and controls and could be performed even in patients with severe expressive aphasia. The analysis agreement between both specialists was substantial for classifying comprehension-positive and -negative sites. Extensive left-hemispheric individual cortical comprehension sites were identified for all patients. Apart from one case presenting with transient worsening of aphasic symptoms, pre-existing language deficits did not aggravate if results were used for subsequent surgical planning. CONCLUSION: Employing this new comprehension-based nTMS setup allowed to identify language relevant cortical sites in all healthy subjects and severely aphasic patients who were thus far precluded from classic production-based mapping. This pilot study, moreover, provides first indications that the CompreTAP mapping results may support the preservation of residual language function if used for subsequent surgical planning.

Presurgical Language Mapping: What Are We Testing?

Gliomas are brain tumors infiltrating healthy cortical and subcortical areas that may host cognitive functions, such as language. If these areas are damaged during surgery, the patient might develop word retrieval or articulation problems. For this reason, many glioma patients are operated on awake, while their language functions are tested. For this practice, quite simple tests are used, for example, picture naming. This paper describes the process and timeline of picture naming (noun retrieval) and shows the timeline and localization of the distinguished stages. This is relevant information for presurgical language testing with navigated Magnetic Stimulation (nTMS). This novel technique allows us to identify cortical involved in the language production process and, thus, guides the neurosurgeon in how to approach and remove the tumor. We argue that not only nouns, but also verbs should be tested, since sentences are built around verbs, and sentences are what we use in daily life. This approach's relevance is illustrated by two case studies of glioma patients.

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.

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.