Model-based geometrical optimisation and in vivo validation of a spatially selective multielectrode cuff array for vagus nerve neuromodulation

•A method for geometric optimisation of neural cuff interfaces is presented.•Multi-electrode cuff array for selective vagus nerve stimulation was optimised.•The array was tested in animals activating isolated cardiac and respiratory effects.•This technique can be applied to study basic neuroscience in autonomic nerves.•It can also be applied to improve the outcome of therapeutic neuromodulation. Neuromodulation by electrical stimulation of the human cervical vagus nerve may be limited by adverse side effects due to stimulation of off-target organs. It may be possible to overcome this by spatially selective stimulation of peripheral nerves. Preliminary studies have shown this is possible using a cylindrical multielectrode human-sized nerve cuff in vagus nerve selective neuromodulation. The model-based optimisation method for multi-electrode geometric design is presented. The method was applied for vagus nerve cuff array and suggested two rings of 14 electrodes, 3 mm apart, with 0.4 mm electrode width and separation and length 0.5−3 mm, with stimulation through a pair in the same radial position on the two rings. The electrodes were fabricated using PDMS-embedded stainless steel foil and PEDOT: pTS coating. In the cervical vagus nerve in anaesthetised sheep, it was possible to selectively reduce the respiratory breath rate (RBR) by 85 ± 5% without affecting heart rate, or selectively reduce heart rate (HR) by 20 ± 7% without affecting respiratory rate. The cardiac- and pulmonary-specific sites on the nerve cross-sectional perimeter were localised with a radial separation of 105 ± 5 degrees (P < 0.01, N = 24 in 12 sheep). Results suggest organotopic or function-specific organisation of neural fibres in the cervical vagus nerve. The optimised electrode array demonstrated selective electrical neuromodulation without adverse side effects. It may be possible to translate this to improved treatment by electrical autonomic neuromodulation for currently intractable conditions.