MRI-guided navigated TMS protocol for language production lateralization in right- and left-handed individuals

Hemispheric language lateralization has been assessed using various neuroimaging techniques in both basic research and clinical settings. The use of transcranial magnetic stimulation (TMS) for this purpose, however, has shown low to moderate concordance with other neuroimaging techniques, particularly in cases of atypical lateralization and when studying the right hemisphere. The present study aimed to develop an MRI-guided navigated TMS protocol based on a verb-generation task to identify optimal conditions for determining language lateralization. Thirty healthy participants were classified into three groups according to hemispheric dominance during the verb-generation task: right-handers with left-hemisphere dominance, left-handers with left-hemisphere dominance, and left-handers with right-hemisphere dominance. TMS was applied at four predetermined locations within the inferior frontal gyrus while participants performed a picture-based verb generation task outside the scanner. Results showed a larger proportion of error responses when TMS was applied to the dominant language hemisphere, as defined by fMRI, across all groups. Concordance values between fMRI and TMS language lateralization ranged from 89% to 100%. Naming times were slower when the dominant hemisphere was stimulated, but only in the left-handed group. Trials more likely to induce TMS-related errors were characterized by longer reaction times, a greater number of response options, lower word frequency, and the absence of a clearly dominant response. These findings support the reliability of the proposed navigated TMS protocol for individual-level assessment of language lateralization during verb generation task as well as identify task-related conditions that increase the likelihood of verbal errors following TMS interference.