Abstract

Transcranial magnetic stimulation (TMS) has become an important technique in both scientific and clinical practices, and yet our understanding of how the brain responds to TMS is still limited. Concurrent neuroimaging during TMS may bridge this gap, and emerging evidence suggests widespread that modulatory effects of TMS may be best captured through changes in functional connectivity between distributed networks, rather than local changes in cortical activity. However, the relationship between TMS stimulation parameters and evoked changes in functional connectivity is unknown. In this study, 24 healthy volunteers received concurrent TMS-fMRI while performing a dot-motion direction discrimination task. An MR-compatible coil was used to apply trains of three pulses at 10 Hz rTMS over the primary visual cortex (V1) at the onset of the dot stimuli with four levels of stimulation intensity (20%, 40%, 80%, and 120% of resting motor threshold, RMT). Behavioral results demonstrated impairment of motion discrimination at 80% RMT. FMRI results yielded three findings. First, functional connectivity between visual and non-visual areas increased as a function of rTMS intensity. Second, connectivity within the visual network was positively associated with motion accuracy, while the connectivity between visual and non-visual regions was negatively associated with motion accuracy. Lastly, we found that reductions in the similarity between functional and structural connectivity associated with increasing TMS intensity were constrained to the visual network. These findings demonstrate spatially dependent nonlinear effects of TMS intensity on brain functional connectivity that proceed beyond the site of stimulation and influence associated behavior.