Development of a single pulse transcranial magnetic stimulation protocol for individual localization of brain regions for semantic processing

Objectives: Repetitive TMS is widely used to interfere with normal language processing by employing rapidly changing magnetic fields. Involuntary contractions of the temporal muscle however make rTMS-effects of temporal language areas difficult to interpret. We thus developed a TMS protocol for investigation of language processing areas using single pulse TMS to avoid interference with articulated speech. It is hypothesized that a single TMS pulse can still interfere with language processing if it is applied in a certain time window after presentation of the language task stimulus. Methods: Language related brain activation in relevant Brodmann areas 45 and 22 was localized using BOLD-Contrast f-MRI during a silent verb generation task in ten right-handed normal subjects (5 f, 5 m) on a clinical 1.5 T scanner (Gyroscan Intera, Philips, Best). A T1-weighted morphological MRI was acquired for anatomical localization. Stimulation points for rTMS were determined on 3D renderings from the morphological MRI-images. Stimulation sites were located using the fMRI and transferred to each subjects head as previously described (Thiel et al, Neuroimage 2005). The right inferior frontal stimulation site was determined anatomically. For the TMS-procedure the coil was placed over the 4 stimulation sites (left and right BA 45, left and right BA 22) and high frequency two-syllable German nouns were presented acoustically. At 100, 150, 200, 250 and 300 ms after the end of the presented noun a single TMS pulse at resting motor threshold intensity was applied. 10 nouns were presented for each stimulation site and each pulse onset interval. Mean verb-generation latencies were compared to latencies without stimulation. Results: The preliminary results indicate a significant increase in reaction time latency during stimulation over right BA 22 with a pulse onset latency of 200ms. Decrease in reaction time latency was observed over left Broca's area at a pulse onset latency of 100 and 200ms. Conclusion: In contrast to repetitive TMS timed single pulses induce inhibitory as well as facilitatory effects over different regions of language relevant networks.