The use of a non-invasive form of energy to modulate neural structures has gained wide spread attention because of its ability to remotely control neural excitation. This study investigates the ability of focused high frequency ultrasound to modulate the excitability the peripheral nerve of an amphibian. A 5MHz ultrasound transducer is used for the study with the pulse characteristics of 57msec long train burst and duty cycle of 8% followed by an interrogative electrical stimulus varying from 30μsecs to 2msecs in pulse duration. The nerve excitability is determined by the compound action potential (CAP) amplitude evoked by a constant electrical stimulus. We observe that ultrasound's immediate effect on axons is to reduce the electrically evoked CAP amplitude and thereby suppressive in effect. However, a subsequent time delayed increased excitability was observed as reflected in the CAP amplitude of the nerve several tens of milliseconds later. This subsequent change from ultrasound induced nerve inhibition to increased excitability as a function of delay from ultrasound pulse application is unexpected and not predicted by typical nerve ion channel kinetic models. The recruitment curve of the sciatic nerve modified by ultrasound suggests the possibility of a fiber specific response where the ultrasound inhibits the faster fibers more than the slower ones. Also, changes in the shape of the CAP waveform when the nerve is under the inhibitive effect of ultrasound was observed. It is postulated that these effects can be a result of activation of stretch activation channels, mechanical sensitivity of the nerve to acoustic radiation pressure and modulation of ion channels by ultrasound.

The neuromodulatory capabilities of ultrasound in tandem with electrical stimulation has a significant potential for development of neural interfaces to peripheral nerve.