Abstract
Ultrasound (US) has been shown to stimulate brain circuits, however, the ability to excite peripheral nerves with US remains controversial. To the best of our knowledge, there is still no in vivo neural recording study that has applied US stimulation to a nerve isolated from surrounding tissue to confirm direct activation effects. Here, we show that US cannot excite an isolated mammalian sciatic nerve in an in vivo preparation, even at high pressures (relative to levels recommended in the FDA guidance for diagnostic ultrasound) and for a wide range of parameters, including different pulse patterns and center frequencies. US can, however, reliably inhibit nerve activity whereby greater suppression is correlated with increases in nerve temperature. By prohibiting the nerve temperature from increasing during US application, we did not observe suppressive effects. Overall, these findings demonstrate that US can reliably inhibit nerve activity through a thermal mechanism that has potential for various health disorders, though future studies are needed to evaluate the long-term safety of therapeutic ultrasound applications.
Highlights
Ultrasound (US) has been shown to stimulate brain circuits, the ability to excite peripheral nerves with US remains controversial
Using pressures up to 5 MPa (ISPTA up to 62.48 W/cm[2] and ISPPA up to 833 W/cm2), which substantially exceeded levels typically used for diagnostic ultrasound (e.g., FDA guidance of ISPTA ≤ 0.72 W/cm[2] and ISPPA ≤ 190 W/cm2), we still could not excite the sciatic nerve even when using a wide range of pulse patterns, including different center frequencies, pulse modes, pulse repetition frequencies (PRFs), and duty cycles tested in our study
Our results are consistent with two studies directly recording nerve activity from completely or partially isolated n erves[17,18], but are inconsistent with published noninvasive studies reporting US nerve excitation based on indirect measures of nerve activity from non-isolated nerves[11,12]
Summary
Ultrasound (US) has been shown to stimulate brain circuits, the ability to excite peripheral nerves with US remains controversial. Other noninvasive US stimulation studies that recorded muscle action potentials as a surrogate for mouse sciatic nerve activity required much higher pressures, such as 13 or 28 MPa, for presumably exciting the nerve Note that these pressures are much higher than the levels recommended in the FDA guidance for diagnostic ultrasound (e.g., intensity of 5633 W/ cm[2] that exceeds 190 W/cm[2], and mechanical index of 6.5 that exceeds 1.913–16). Our results reveal that: (1) US activates the skin, surrounding tissue and/or muscles but cannot directly excite the myelinated sciatic nerve with numerous parameters tested using different US transducers and center frequencies; (2) US reliably inhibits nerve activity but direct enhancement of nerve activity is not possible; and (3) greater suppression of nerve activity is accompanied by larger increases in nerve temperature
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