The cortical representation of transitivity: Insights from tractography-based inhibitory nTMS.

Navigated Transcranial Magnetic Stimulation (nTMS) is commonly used to causally identify cortical regions involved in language processing. Combining tractography with nTMS has been shown to increase induced error rates by targeting stimulation of cortical terminations of white matter fibers. According to functional Magnetic Resonance Imaging (fMRI) data, bilateral cortical areas connected by the arcuate fasciculus (AF) have been implicated in the processing of transitive compared to unergative verbs. To test this connection between transitivity and bilateral perisylvian regions, we administered a tractography-based inhibitory nTMS protocol during action naming of finite transitive (The man reads) and unergative (The man sails) verbs. After tracking the left and right AF, we stimulated the cortical terminations of the tract in frontal, parietal and temporal regions in 20 neurologically healthy native speakers of German. Results revealed that nTMS induced more errors during transitive compared to unergative verb naming when stimulating the left (vs right) AF terminations. This effect was specific to the left temporal terminations of the AF, whereas no differences between the two verb types were identified when stimulating inferior parietal and frontal AF terminations. Induced errors for transitive verbs over left temporal terminations mostly manifested as access errors (i.e., hesitations). Given the inhibitory nature of our nTMS protocol, these results suggest that temporal regions of the left hemisphere play a crucial role in argument structure processing. Our findings align with previous data on the role of left posterior temporal regions in language processing and by providing further evidence from a language production experiment using tractography-based inhibitory nTMS.

Verb and sentence processing with TMS: A systematic review and meta-analysis.

Transcranial magnetic stimulation (TMS) has provided relevant evidence regarding the neural correlates of language. The aim of the present study is to summarize and assess previous findings regarding linguistic levels (i.e., semantic and morpho-syntactic) and brain structures utilized during verb and sentence processing. To do that, we systematically reviewed TMS research on verb and sentence processing in healthy speakers, and meta-analyzed TMS-induced effects according to the region of stimulation and experimental manipulation. Findings from 45 articles show that approximately half of the reviewed work focuses on the embodiment of action verbs. The majority of studies (60%) target only one cortical region in relation to a specific linguistic process. Frontal areas are most frequently stimulated in connection to morphosyntactic processes and action verb semantics, and temporoparietal regions in relation to integration of sentential meaning and thematic role assignment. A meta-analysis of 72 effect sizes of the reviewed papers indicates that TMS has a small overall effect size, but effect sizes for anterior compared to posterior regions do not differ for semantic or morphosyntactic contrasts. Our findings stress the need to increase the number of targeted areas, while using the same linguistic contrasts in order to disentangle the contributions of different cortical regions to distinct linguistic processes.

Lesion-symptom mapping of language impairments in people with brain tumours: The influence of linguistic stimuli.

People with tumours in specific brain sites might face difficulties in tasks with different linguistic material. Previous lesion-symptom mapping studies (VLSM) demonstrated that people with tumours in posterior temporal regions have more severe linguistic impairments. However, to the best of our knowledge, preoperative performance and lesion location on tasks with different linguistic stimuli have not been examined. In the present study, we performed VLSM on 52 people with left gliomas to examine whether tumour distribution differs depending on the tasks of the Aachen Aphasia Test. The VLSM analysis revealed that single-word production (e.g. object naming) was associated with the inferior parietal lobe and that compound and sentence production were additionally associated with posterior temporal gyri. Word repetition was affected in people with tumours in inferior parietal areas, whereas sentence repetition was the only task to be associated with frontal regions. Subcortically, word and sentence production were found to be affected in people with tumours reaching the arcuate fasciculus, and compound production was primarily associated with tumours affecting the inferior longitudinal and inferior fronto-occipital fasciculus. Our work shows that tasks with linguistic stimuli other than single-word naming (e.g. compound and sentence production) relate to additional cortical and subcortical brain areas. At a clinical level, we show that tasks that target the same processes (e.g. repetition) can have different neural correlates depending on the linguistic stimuli used. Also, we highlight the importance of left temporoparietal areas.

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.

Support vector machine based aphasia classification of transcranial magnetic stimulation language mapping in brain tumor patients.

Repetitive TMS (rTMS) allows for non-invasive and transient disruption of local neuronal functioning. We used machine learning approaches to assess whether brain tumor patients can be accurately classified into aphasic and non-aphasic groups using their rTMS language mapping results as input features. Given that each tumor affects the subject-specific language networks differently, resulting in heterogenous rTMS functional mappings, we propose the use of machine learning strategies to classify potential patterns of rTMS language mapping results. We retrospectively included 90 patients with left perisylvian world health organization (WHO) grade II-IV gliomas that underwent presurgical navigated rTMS language mapping. Within our cohort, 29 of 90 (32.2%) patients suffered from at least mild aphasia as shown in the Aachen Aphasia Test based Berlin Aphasia Score (BAS). After spatial normalization to MNI 152 of all rTMS spots, we calculated the error rate (ER) in each stimulated cortical area (28 regions of interest, ROI) by automated anatomical labeling parcellation (AAL3) and IIT. We used a support vector machine (SVM) to classify significant areas in relation to aphasia. After feeding the ROIs into the SVM model, it revealed that in addition to age (w = 2.98), the ERs of the left supramarginal gyrus (w = 3.64), left inferior parietal gyrus (w = 2.28) and right pars triangularis (w = 1.34) contributed more than other features to the model. The model's sensitivity was 86.2%, the specificity was 82.0%, the overall accuracy was 85.5% and the AUC was 89.3%. Our results demonstrate an increased vulnerability of right inferior pars triangularis to rTMS in aphasic patients due to left perisylvian gliomas. This finding points towards a functional relevant involvement of the right pars triangularis in response to aphasia. The tumor location feature, specified by calculating overlaps with white and grey matter atlases, did not affect the SVM model. The left supramarginal gyrus as a feature improved our SVM model the most. Additionally, our results could point towards a decreasing potential for neuroplasticity with age.