Chronic subthreshold rTMS transiently disrupts learning but enhances memory and flexibility in healthy rats

Objective Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-invasive neuromodulation technique with therapeutic potential for the treatment of cognitive disorders. However, its effects on fundamental learning and memory processes in the healthy brain remain poorly understood. We have previously shown that subthreshold rTMS delivered with a miniaturized coil modulates neuronal activities and evoked potentials, but whether these physiological effects translate into cognitive changes remains unknown. Here, we systematically characterize the effects of subthreshold rTMS on learning and memory in healthy rats. Approach We examined both chronic and acute effects of high-frequency (10 Hz) subthreshold rTMS on spatial learning, memory, and cognitive flexibility in healthy rats performing the Barnes maze task. The stimulation was delivered to the prefrontal cortex using the miniaturized coil, whose focal design operates at subthreshold intensity. Main results We found that chronic rTMS transiently disrupted early spatial learning during the acquisition phase but did not impair overall task performance. In contrast, rTMS was associated with enhanced cognitive flexibility during the first reversal-learning phase and strengthened spatial memory of prior target locations during acquisition and reversal probe trials. These effects were not detected in the exploratory second reversal phase, and no acute cognitive effects were detected under alternating rTMS and sham stimulation. Together, these findings suggest complex, phase-specific effects of subthreshold rTMS on rodent cognition: transiently hindering early learning while promoting memory retention and flexibility. Significance This work highlights both the opportunities and challenges of rTMS for cognitive modulation and provides a translational framework for optimizing stimulation protocols in neuropsychiatric and neurodegenerative disorders.