  Background. 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. New method. 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. Results. 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). Conclusions.
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.
