Ultra-High Frequency-Low Intensity Magnetic Stimulation Enhances Functional Recovery in a Rat Model for Chronic...

Stroke causes motor and cognitive impairments. Neural stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) has shown promise in rehabilitating impaired neural functions. However, despite the reported efficacies, stimulus parameters (i.e., applied field amplitude, frequency, and duration) are loosely defined and carry the risk of non-localized heat dissipation, seizure, and scalp discomfort due to high field intensities and direct contact of the devices with the scalp. To advance stroke therapy and to minimize their associated risks, we are exploring an alternative neuromodulation strategy termed ultra high frequency-low intensity magnetic stimulation (UHF-LiMS) designed to enhance functional recovery. For preclinical assessment, focal infarction was induced via photothrombosis in the internal capsule area of the subcortex in male Sprague-Dawley rats, a region well-documented for suppressing spontaneous longitudinal recovery. Sinusoidal magnetic fields (3-10 mT peak amplitude, 400 kHz) were applied, and functional recovery was assessed behaviorally and via imaging. In addition, longitudinal [ $^{\wedge}$ 18F]-FDG microPET scans and immunohistochemical analysis of c-Fos expression were used to evaluate metabolic activity and neural activation at cellular level. Magnetic stimulation induced substantial somatomotor and somatosensory recovery, with behavioral scores improving by up to ~70% of pre-infarct levels. PET imaging showed reduced stroke-induced diaschisis and increased cortical and subcortical metabolic activity with statistically significant correlations. Elevated c-Fos expression in both cortical and subcortical regions indicates enhanced neuronal activation, serving as a transcriptional signature of neural plasticity. Our study demonstrates that UHF-LiMS effectively restores motor and sensory functions in a white matter stroke model, highlighting its therapeutic potential as a neurostimulation technique.