Resting‐State Functional Magnetic Resonance Imaging Reveals the Effects of rTMS on Neural Activity and Brain Connectivity After Experimental Stroke

ABSTRACT Aims Limited understanding of neurobiological mechanisms of repetitive transcranial magnetic stimulation (rTMS) prevents us from choosing optimal therapeutic regimen for patients to improve therapeutic efficiency. Resting‐state functional magnetic resonance imaging (rs‐fMRI) has been demonstrated to obtain comparable functional readouts across species. Methods Intermittent and continuous theta burst stimulation were used to stimulate ipsilesional and contralesional hemisphere, respectively, during the subacute phase after stroke. We used a rat middle cerebral artery occlusion stroke model. The amplitude of low‐frequency fluctuations and functional connectivity analyses of rs‐fMRI were chosen to detect neuron activity and functional connectivity. The expression of neuron activation marker c‐Fos and axonal plasticity marker GAP43 was examined by an immunochemistry method to corroborate the results of rs‐fMRI. Results iTBS altered the long‐term neuronal activity in bilateral sensorimotor cortex, whereas cTBS influenced immediate neuronal activity of bilateral sensorimotor cortex. In addition, cTBS enhanced interhemispheric and intrahemisheric functional connectivity in contralesional hemisphere, accompanied by axonal and dendritic remodeling in the perilesional cortical areas and contralesional homologous areas after large stroke. Conclusion rTMS exerted complex effects on brain structural and functional connectivity in addition to affecting cortical excitability. cTBS promoted the compensatory effect of contralesional hemisphere after stroke with large lesions.