Development and in silico validation of innovative technological approaches to improve vagus nerve stimulation protocols

Vagus nerve stimulation (VNS) is a well-established therapeutic tool for treating various disorders, including epilepsy, depression, and chronic inflammatory conditions such as heart failure, inflammatory bowel disease, and rheumatoid arthritis. Despite its widespread use, current VNS approaches rely on cuff electrodes that stimulate the entire nerve with pre-set parameters, often resulting in off-target effects and suboptimal therapeutic outcomes. Advanced neural interfaces that account for the fascicular organization of the vagus nerve could enable real-time monitoring of changes in vagal signaling. This would allow adaptive stimulation protocols tailored to individual patient needs, mimicking the physiological activation patterns of healthy nerve fibers and improving the clinical efficacy of VNS. Here, we explored advanced technological strategies to autonomously achieve a highly selective, stable, and safe interaction with vagus nerve fascicles. Compared to traditional cuff electrodes and transverse intrafascicular multichannel electrodes (TIME), the proposed technology offers superior selectivity and spatial resolution when targeting highly fasciculate peripheral nerves such as the vagus. The chosen materials and innovative implantation strategy potentially reduce nerve damage induced by stiff penetrating multichannel silicon probes, ensuring long-term stability with minimal invasiveness. Additionally, a highly scalable fabrication process allows for the precise customization to specific vagus nerve branches according to clinical requirements. In silico models were employed to validate the outcomes of the proposed technology. A computational framework was first developed to simulate the vagus nerve using human anatomical data. This framework was then used to evaluate the activation of specific vagus nerve fibers during both stimulation and recording experiments. Finally, the selectivity performance of this approach was compared to cuff electrodes and TIME, demonstrating its potential advantages. This study represents a technological advancement in the application of bioelectronic medicine for vagus nerve modulation, paving the way for more effective and personalized vagus nerve therapies in clinical settings.