Functional MRI reveals regional changes of brain activity in rats following longitudinal focal high-density theta...

The therapeutic benefits of transcranial magnetic stimulation (TMS) are believed to stem from neuroplasticity induced by repeated sessions. While animal models have contributed to our understanding of TMS-induced plasticity, there is a need for a rodent model that closely replicates the prolonged conditions experienced by humans. This study aimed to develop a rat model that reflects the spatial and temporal dynamics of human TMS protocols and to evaluate the carryover effects of TMS on the brain at a systems level. Experiments were carried out on two groups of rats (N = 33). In the first cohort, rats were implanted with microwire electrodes to record motor-evoked potential (MEP) signals and received daily sessions of high-density theta burst stimulation (hdTBS) for 5 days. Cortical excitability was assessed through input-output (I-O) curves before and after hdTBS (Day 0 and Day 6). To identify brain regions affected by the longitudinal TMS, the second cohort underwent identical TMS protocol and received fMRI scans on Days 0 and 6 to measure basal cerebral blood volume (CBV). Results reveal that daily hdTBS significantly shifted I-O curves upward in the TMS group (N = 9) compared to the sham group (N = 7), reflecting enhanced cortical excitability. Additionally, fMRI data showed elevated basal CBV in both the stimulation sites and in the connected networks (N = 8 for active TMS and N = 9 for sham), suggesting increased basal metabolism. This study opens a novel platform for further exploring the mechanisms underlying TMS-induced plasticity.