Selective, epineural stimulation of peripheral nerves with interferential electrical fields - Selective, epineural stimulation of peripheral nerves with interferential electrical fields Project Summary/Abstract Most existing PNS interfaces do not adequately target nerve fibers mediating specific physiological functions and innervating specific organs or muscles. Nonselective activation of nerve fibers may lead to reduced PNS efficacy and unwanted side effects. PNS that selectively activates specific fiber populations in a nerve would be desirable for mechanistic and translational studies but is not currently feasible. The anatomical organization of autonomic (e.g., the vagus nerve, VN) and somatic nerves (e.g., the femoral nerve, FN) is amenable to fascicular neurostimulation using multi-contact cuff electrodes (MCEs), which have a favorable safety profile. We hypothesize that multi-source, intermittent interferential current stimulation (i2CS) delivered through an MCE that accommodates the fascicular anatomy of the nerve is a viable strategy for PNS, superior to current state-of-the-art methods. Aim 1 will test the hypothesis that interference arising from superposition of currents of slightly different frequencies delivered through separate electrode contacts, focuses electric fields and selectively activates specific fascicles inside the trunk of multi-fascicular nerves. It will also establish that i2CS is superior to other methods of PNS and characterize how stimulation parameters affect efficacy and selectivity. Aim 2 will develop and validate a design methodology, based on computer simulations of nerve interfaces, for determining the preferred contact configuration of an MCE for effective iCS delivered to a given autonomic or somatic nerve. It will also develop and validate a methodology for optimizing i2CS stimulation paradigm on an individual subject basis. In the long run, PNS targeting specific fiber populations could improve efficacy and safety of existing therapies and open up new therapeutic indications.