Bipolar cancellation is unique to nsEP and is manifested by profound reduction of biological efficiency if the nsEP polarity is reversed. The bipolar cancellation was demonstrated for effects, from Ca2+ mobilization in excitable and non-excitable cells, to membrane permeabilization and cell death induction. We work towards elucidating the mechanisms responsible for bipolar cancellation and utilize it for biophysical research of excitation and fast ion channel kinetics.
We also develop a new paradigm of focused remote stimulation based on bipolar cancellation. We propose to minimize stimulation near pulse-delivering electrodes by applying bipolar nsEP, whereas the superposition of two phase-shifted bipolar nsEP from two independent sources yields a biologically-effective unipolar pulse remotely. This is accomplished by electrical compensation of all nsEP phases except the first one, resulting in the restoration of stimulation efficiency due to cancellation of bipolar cancellation (a CANCAN effect). CANCAN is promising for non-invasive deep tissue stimulation, either alone or combined with other remote stimulation techniques to improve targeting.
