Background and purpose: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique used to treat many neurological and psychiatric conditions. Even though rTMS is being used in a clinical setting, little is known about the mechanisms underlying its mode of action. Here we use non-invasive resting state fMRI (rs-fMRI) to examine the effects of low-intensity rTMS in Sprague Dawley rats, setting the scene for direct comparisons between rodent and human studies.
Methods: rs-fMRI data were acquired at 9.4 T before and after 10 minutes of control or rTMS with one of four stimulation protocols commonly used to elicit cortical inhibition or excitation. We used independent component analysis as implemented in FSL to uncover changes in the default mode network (DMN) induced by each rTMS protocol.
Results: There were considerable changes in the rat DMN induced by rTMS: (i) the synchrony of resting activity of the somatosensory cortex was decreased ipsilaterally following 10 Hz stimulation, increased ipsilaterally following continuous theta burst stimulation (cTBS), and decreased bilaterally following 1 Hz stimulation and biomimetic high frequency stimulation (BHFS); (ii) the motor cortex showed bilateral changes following 1 Hz and 10 Hz stimulation, an ipsilateral increase in synchrony following cTBS, and a contralateral decrease following BHFS; and (iii) in the hippocampus, 10 Hz stimulation caused an ipsilateral decrease while 1 Hz and BHFS caused a bilateral decrease in synchrony.
Conclusion: The present findings suggest that rTMS modulates functional links within the DMN of rats with frequency specific outcomes. Observed changes in the resting-state network of the rodent brain are similar to those described in the human brain following rTMS. Hence, combined rTMS-fMRI emerges as a powerful tool to investigate rTMS-induced cortical connectivity changes in rodents and humans at a high spatio-temporal resolution.