Direct electrical stimulation of the seizure focus can achieve the early termination of epileptic oscillations. However, direct intervention of the hippocampus, the most prevalent seizure focus in temporal lobe epilepsy is thought to be not practicable due to its large size and elongated shape. Here, in a rat model, we report a sequential narrow-field stimulation method for terminating seizures, while focusing stimulus energy at the spatially extensive hippocampal structure. The effects and regional specificity of this method were demonstrated via electrophysiological and biological responses. Our proposed modality demonstrates spatiotemporal preciseness and selectiveness for modulating the pathological target region which may have potential for further investigation as a therapeutic approach.

Transcranial electrical stimulation (TES) is a widely accepted neuromodulation modality for treating brain disorders. However, its clinical efficacy is fundamentally limited due to the current shunting effect of the scalp and safety issues. A newer electrical stimulation technique called subcutaneous electrical stimulation (SES) promises to overcome the limitations of TES by applying currents directly at the site of the disorder through the skull. While SES seems promising, the electrophysiological effect of SES compared to TES is still unknown, thus limiting its broader application. Here we comprehensively analyze the SES and TES to demonstrate the effectiveness and advantages of SES. Beagles were bilaterally implanted with subdural strips for intracranial electroencephalography and electric field recording. For the intracerebral electric field prediction, we designed a 3D electromagnetic simulation framework and simulated TES and SES. In the beagle model, SES induces three to four-fold larger cerebral electric fields compared to TES, and significant changes in power ratio of brainwaves were observed only in SES. Our prediction framework suggests that the field penetration of SES would be several-fold larger than TES in human brains. These results demonstrate that the SES would significantly enhance the neuromodulatory effects compared to conventional TES and overcome the TES limitations.

As transcranial electrical stimulation (tES) is an emerging and promising technique for neuromodulation, we developed a novel device; wirelessly-powered, extracranial brain activator (ECBA), which is mounted subcutaneously, and its neuromodulation effect was investigated. The oscillatory changes in electrocorticography (EcoG) were analyzed from two types of stimulation. Two weeks prior to the recording experiment, we underwent surgery for implantation of subdural strips and ECBA module over centroparietal regions of anesthetized beagles. Low-frequency stimulation (LFS) and subsequent high-frequency stimulation (HFS) protocols (600 pulses respectively) were applied. Then, the power changes before and after each stimulation in five different bands were compared. A significantly larger voltage difference with subcutaneous than transcutaneous stimulation measured at EcoG channels indicated a substantial current attenuation between the skin and skull. Compared with the baseline, all subjects showed consistently decreased delta power and increased gamma power after HFS. LFS also induced a similar, but opposite, pattern of power change in four beagles. The results from this study indicate that LFS and HFS with our novel ECBA can consistently and effectively modulate neural activity of the cortex, inducing neural inhibition and facilitation functions, respectively. Future studies are necessary to further ensuring a consistent efficacy and long-term safety.

The present study aimed to evaluate a new tibial nerve stimulation (TNS) modality, which uses interferential currents, in terms of the stimulation electric field penetration efficiency into the body and physiological effectiveness. Methods: In silico experiments were performed to analyze the penetration efficiency of proposed interferential current therapy (ICT). Based on this, we performed in vivo experiments to measure excitation threshold of ICT for the tibial nerve, which is related to stimulation field near the nerve. Regarding analysis of the physiological effectiveness, in vivo ICT-TNS was performed, and changes in bladder contraction frequency and voiding volume were measured. The penetration efficiency and physiological effectiveness of ICT were evaluated by comparison with those of conventional TNS using transcutaneous electrical nerve stimulation (TENS). Results: Simulation results showed that ICT has high penetration efficiency, thereby generating stronger field than TENS. These results are consistent with the in vivo results that nerve excitation threshold of ICT is lower than that of TENS. Moreover, ICT-TNS decreased contraction frequency and increased voiding volume, and its performance was profound compared with that of TENS-TNS. Conclusion: The proposed ICT is more efficient in inducing the stimulation field near the tibial nerve placed deep inside the body compared with conventional TENS and shows a good clinical effectiveness for TNS. Significance: The high efficiency of ICT increases the safety of noninvasive neurostimulation; therefore, it has clinical potential to become a promising modality for TNS to treat OAB and other peripheral neurostimulations.