Background and purpose: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique used to treat many neurological and psychiatric conditions. However, not much is known about the mechanisms underlying its efficacy because human rTMS studies are mostly non-invasive while most animal studies are invasive. Invasive animal studies allow for cellular and molecular changes to be detected and hence, have been able to show that rTMS may alter synaptic plasticity in the form of long-term potentiation. This is the first rodent study using non-invasive resting state functional magnetic resonance imaging (rs-fMRI) to examine the effects of low-intensity rTMS (LI-rTMS) in order to provide a more direct comparison to human studies.
Methods: rs-fMRI data were acquired before and after 10 minutes of LI-rTMS intervention at one of four frequencies—1 Hz, 10 Hz, biomimetic high frequency stimulation (BHFS) and continuous theta burst stimulation (cTBS)—in addition to sham. We used independent component analysis to uncover changes in the default mode network (DMN) induced by each rTMS protocol.
Results: There were considerable rTMS-related changes in the DMN. Specifically, (1) the synchrony of resting activity of the somatosensory cortex was decreased ipsilaterally following 10 Hz stimulation, increased ipsilaterally following cTBS, and decreased bilaterally following 1 Hz stimulation and BHFS; (2) the motor cortex showed bilateral changes following 1 Hz and 10 Hz stimulation, an ipsilateral increase in synchrony of resting activity following cTBS, and a contralateral decrease following BHFS; and (3) in the hippocampus, 10 Hz stimulation caused an ipsilateral decrease while 1 Hz and BHFS caused a bilateral decrease in synchrony. There was no change in the correlation of the hippocampus induced by cTBS.
Conclusion: The present findings suggest that LI-rTMS can modulate functional links within the DMN of rats. LI-rTMS can induce changes in the cortex, as well as in remote brain regions such as the hippocampus when applied to anaesthetised rats and the pattern of these changes depends on the frequency used, with 10 Hz stimulation, BHFS and cTBS causing mostly ipsilateral changes in synchrony of activity in the DMN and 1 Hz stimulation causing bilateral changes in synchrony, with the contralateral changes being more prominent than ipsilateral changes. Hence, combined rTMS-fMRI emerges as a powerful tool to visualise rTMS-induced cortical connectivity changes at a high spatio-temporal resolution and help unravel the physiological processes underlying these changes in the cortex and interconnected brain regions
