Functional MRI reveals regional changes of brain activity in rats following longitudinal focal high-density theta burst stimulation (hdTBS).

Abstract

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.