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Objective Functional magnetic resonance imaging (fMRI) is widely used for mapping of language areas. However, depending on the task design and the region of interest, a clear identification of language relevant areas can be challenging. We, therefore, compared three different fMRI task designs, i.e., picture naming and listening to simple vs. complex sentences followed by a non-verbal semantic decision task, for delineating cortical language areas. Methods 20 right-handed, healthy volunteers were investigated using fMRI (3T) with a sparse-sampling design (controlling for speech-related movement artefacts). In the first task, subjects were asked to name objects which were presented as black-white drawings by speaking out loudly a whole sentence introduced by the phrase ‘That is a/an…’. In the other paradigms, subjects were listening to simple or complex sentences (spoken by a male or female voice) followed by a semantic decision task. Here, three pictures were presented 5s after the sentences and subjects were asked to choose the corresponding item via button press. FMRI activation levels corresponding to the semantic decision after listening to meaningful sentences were compared to a control condition (i.e., listening to reverse sentences). fMRI data were analyzed using SPM12. Results The three language tasks differently activated regions engaged in the language network. Of note, listening to complex sentences led to a significantly higher activation during the semantic decision within the inferior frontal gyrus (IFG) as compared to simple sentences (p Conclusion Our results show that the activation of language-relevant areas depends strongly on the design of the fMRI task and indicate that activation within Broca’s area (IFG) increases with the complexity of the semantic decision.

Objective The preservation of important white matter tracts is extremely important to optimize the functional long-term outcome after brain tumour surgery. The integration of functional localizer data such as navigated transcranial magnetic stimulation (nTMS) as starting region of interest (ROI) within the primary motor cortex (M1) into diffusion-tensor-imaging- (DTI-) tractography algorithms represents a recent advancement of the methodology with regard to the reconstruction of the corticospinal tract (CST). We here studied the use of a single nTMS-derived seeding ROI of M1 of the tongue to reconstruct connected fibres of the motor-speech network. Methods 13 healthy volunteers were investigated by nTMS mapping of M1. The hotspot, i.e. the cortical site of the highest motor evoked potential (MEP) amplitude, of the tongue representation was localized. The 3D-coordinate of the respective voxel (site of maximum calculated electrical-field strength) was obtained and was enlarged by a radius of 5 mm. This spheric ROI, representing M1 of the tongue, served as origin for probabilistic fibre tracking (FSL). The reconstructed fibres were segmented according to anatomical knowledge. Moreover, the tractography result was compared to the ”traditional” approach using and anatomical seeding-ROI of equivalent size and depth. Tracts were visualized using MRIcron and Slicer (3D). Results Segments of the arcuate fasciculus (AF) could be reconstructed in all subjects using the single M1-tongue-ROI. Most prominently, the anterior segment of the AF was observed, linking the triangular and opercular part of the inferior frontal gyrus (IFG), i.e., Broca’s territory, with the inferior parietal lobule (85% of cases). Moreover, also the long segment of the AF, connecting the IFG to the angular and dorsal superior temporal gyrus, could be displayed in most cases (92% of cases). Besides several motor pathways like the CST, other tracts involved in language/speech processing were reconstructed using this approach, e.g., the left frontal aslant tract (85% of cases) for which a crucial involvement in speech production (verbal fluency) has been described. Preliminary results regarding diffusion metrics and numbers of aberrant fibres point towards the use of nTMS for seeding-ROI determination being more specific as compared anatomical ROI-seeding. Conclusions Implementing the M1 hotspot of the tongue as a unique seeding-ROI for probabilistic diffusion tractography allows for depiction of motor-speech associated fibres, particularly the anterior segment of the AF. In comparison to anatomical ROI-seeding, this approach may offer a higher specificity and thus avoid aberrant fibre reconstruction, particularly in areas of unfavorable signal-to-noise-ratio.

Objective Using neuronavigated repetitive transcranial magnetic stimulation (rTMS) to disrupt language function during an online-task (e.g., picture naming) is a novel mapping technique which has recently been introduced for presurgical diagnostics in brain tumor patients. However, the method has some limitations due to its rather low specificity. Beyond its dependency on the task, the distinct error categories may have a major effect on the mapping results. We, here, studied the reliability and the spatial localization of rTMS-induced naming errors related to motor-speech function in contrast to semantic language errors. Methods 13 right-handed, healthy volunteers were investigated in 3 consecutive sessions (short-term: 2–5 days, long-term: 21–40 days) by 10 Hz-rTMS. First, the primary motor representation of the face (M1) was mapped by single-pulse TMS. Then, the minimal stimulation intensity which was required to disrupt rhythmic tongue movements by at least three out of five consecutive stimulations over the M1 hotspot was assessed by two independent observers. The “motor inhibition threshold” (MIT) determined the stimulation intensity for the following rTMS language mapping. Online-rTMS was then applied during a picture-naming task using black-and-white drawings of everyday objects which were presented simultaneously (triggered, delay = 0 ms) with the rTMS. The rTMS bursts lasted for 1.5 s (15 pulses). The continuous stimulated area of the left hemisphere had the following anatomical boundaries: middle temporal sulcus (caudal), angular gyrus/ middle parietal sulcus (mediodorsal), hand knob and middle frontal sulcus (medial), triangular part of the inferior frontal gyrus (rostral). Errors were rated by two independent raters by post hoc video analysis. The error frequency (number of errors per 100 TMS trains) as well as the spatial representation and the reliability of distinct motor-speech-related errors, i.e., speech arrest and dysarthria, were compared to language errors associated with semantic processing, i.e., anomia and semantic paraphasia. Test-retest-reliability was assessed by the average intraclass correlation coefficient for a fixed rater (ICC). Results Overall, speech/ language errors were rare events. Amongst the four analyzed error categories, dysarthria represented the most frequent error ( 4.0 ± 2.5 % ) whereas only very few semantic paraphasias were induced ( 0.5 ± 0.4 % ). Motor-speech errors were found significantly more often than semantic language errors ( p 0.01 ). In comparison to semantic errors, the test-retest-reliability of the error rates was lower for motor-speech errors (ICC = 0.45 vs. 0.64). By contrast, the spatial reliability was higher for motor speech errors and showed a strong clustering over M1 and the premotor cortex, especially for the category “arrest”. Conclusion RTMS language mapping is a promising novel technique but the results are still hard to interpret and highly variable. The great majority of errors seems to be at least partially due to motor network disruption rather than being induced by interference with language processing. Further studies, combining different neuroimaging techniques and online-EEG, are mandatory to gain further insight into the underlying mechanisms and the brain-state-dependency of rTMS during language tasks.

Introduction Intermittent theta-burst stimulation (iTBS) effectively increases cortical excitability within the human brain (Huang et al., 2005). However, individual after-effects of iTBS vary between subjects, with a large proportion not responding at all in terms of changes in excitability (Ridding and Ziemann, 2010; Hamada et al., 2013). We here investigated whether subjects responding to iTBS show differential changes in resting-state functional connectivity (rsFC) within the cortical motor system compared to subjects with no response and whether the application of multiple iTBS-blocks can alter responsiveness. Methods We used a sham-stimulation controlled, single-blinded within-subject design to test for iTBS after-effects on (i) motor evoked potentials (MEPs) and (ii) resting-state functional connectivity (rsFC) in 16 healthy, right-handed subjects ( m =7, 27±3years). iTBS was applied over the left primary motor cortex (M1-iTBS) and over the parieto-occipital vertex (sham-iTBS) in separate sessions. In each stimulation session three iTBS blocks were applied, separated by 15min. Seed-based whole-brain rsFC was computed for the stimulated M1. Results Subjects were divided into groups of responders ( n =7) and non-responders ( n =9) according to iTBS-induced changes in MEPs (criterion: increase of at least 10% compared to baseline; Hinder et al., 2014). Increases in MEP-amplitudes following all three M1-iTBS blocks compared to sham-iTBS could exclusively be found for responders. Likewise, rsFC between M1 and premotor areas was significantly higher in responders after all three iTBS blocks ( p ⩽0.05, cluster-level FWE-corrected), whereas no significant increases could be found for the non-responder group. Dose-dependent increases in MEP-amplitudes and rsFC could also only be found for responders. Importantly, non-responders featured higher levels of pre-interventional rsFC compared to responders ( p ⩽0.01, cluster-level FWE-corrected). Individual changes in MEPs and rsFC did not correlate. Discussion Significant iTBS-induced modulations of rsFC and MEP-amplitudes were exclusively found for the responder group, suggesting that responsiveness to iTBS is paralleled by differential changes in motor network connectivity. However, there was no linear correlation between changes in MEP-amplitudes and rsFC. Additional iTBS blocks did not cause a conversion from non-responders to responders, but rather enhanced cortical excitability and rsFC in responders. Furthermore, lower levels of pre-interventional rsFC might contribute to better effectiveness of iTBS.