Complete optimisation and in-vivo validation of the spatially selective multielectode array for vagus nerve 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 nerve cuff optimised for human vagus nerve selective neuromodulation. The design was optimised initially by computer modelling. This 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 stanless steel foil and PEDOT: pTS coating. In the cervical vagus nerve in anesthetised sheep, it was possible to selectively reduce the respiratory rate by 85 +/- 5 % without affecting heart rate, or selectively reduce heart rate by 20 +/- 7 % without affecting respiratory. The cardiac- and pulmonary-specific sites were localised peripherally with a radial separation of 105 +/- 5 degrees and did not intersect (P < 0.01, N = 24, in 12 sheep). This suggests there is organotopic organisation of neural fibres in the cervical vagus nerve. It demonstrates for the first time 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.