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

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

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

Decreased Secondary Lesion Growth and Attenuated Immune Response after Traumatic Brain Injury in Tlr2/4(-/-) Mice

Danger-associated molecular patterns are released by damaged cells and trigger neuroinflammation through activation of non-specific pattern recognition receptors, e. g., toll-like receptors (TLRs). Since the role of TLR2 and 4 after traumatic brain injury (TBI) is still unclear, we examined the outcome and the expression of pro-inflammatory mediators after experimental TBI in Tlr2/4(-/-) and wild-type (WT) mice. Tlr2/4(-/-) and WT mice were subjected to controlled cortical injury and contusion volume and brain edema formation were assessed 24 h thereafter. Expression of inflammatory markers in brain tissue was measured by quantitative PCR 15 min, 3 h, 6 h, 12 h, and 24 h after controlled cortical impact (CCI). Contusion volume was significantly attenuated in Tlr2/4(-/-) mice (29.7 +/- 0.7 mm3 as compared to 33.5 +/- 0.8 mm(3) in WT;p < 0.05) after CCI while brain edema was not affected. Only interleukin (IL)-1 beta gene expression was increased after CCI in the Tlr2/4(-/-) relative to WT mice. Inducible nitric oxide synthetase, TNF, IL-6, and COX-2 were similar in injured WT and Tlr2/4(-/-) mice, while the increase in high-mobility group box 1 was attenuated at 6 h. TLR2 and 4 are consequently shown to potentially promote secondary brain injury after experimental CCI via neuroinflammation and may therefore represent a novel therapeutic target for the treatment of TBI

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