Calibration of a biophysical model to replicate evoked compound action potentials in the swine vagus nerve

Vagus nerve stimulation (VNS) is a promising application of bioelectronic medicine to treat many pathologies, ranging from epilepsy and depression to cardiovascular diseases. Conventional VNS is not optimized taking into account the topographic organization of the vagus nerve, resulting in suboptimal stimulation protocols, which can lead to severe adverse effects. The development of in vivo methods to determine topographic organization would allow more selective stimulation protocols and is thus pivotal in the development of future therapies. Here, we show that it may be possible to reverse-engineer vagus nerve topographic organization starting from experimental evoked compound action potentials (ECAPs). The parameters of a biophysical model of ECAP generation are varied until the optimal matching between synthetic and experimental ECAPs is determined. In the present work, we managed to match an experimental ECAP obtained from swine VNS, and to replicate the shape of an unseen experimental ECAP through the optimized parameters. This work paves the way to the automatic optimization of selective VNS protocols, opening to new important therapeutic opportunities.