Figure 1

Experimental setup with example neural responses. (A) Noninvasive stimulation with skin, muscle, and nerve intact. The transducer was positioned above the skin overlying the sciatic nerve and coupled with agar. (B) Invasive stimulation with the transducer positioned in the muscle cavity over the exposed sciatic nerve and coupled to the nerve with agar. (C) Invasive stimulation with the sciatic nerve “hammocked” by the transducer with parafilm to isolate the nerve from the surrounding tissue to obtain nerve recordings with minimal contamination from non-nerve activity and to maximize the amount of ultrasound (US) energy that reaches the nerve versus the surrounding tissue/muscle (i.e., US waves do not readily travel through air). Somatosensory cortex (SSC) responses for A to C were recorded using the setup shown in D with a 32-site electrode array (4 shanks, 8 sites per shank) inserted into the SSC and in response to US stimulation (1 MPa, 200 Hz pulse repetition frequency [PRF], 2.5 ms pulse duration [PD], 10 pulses, 1 s trial duration [TD], 0.22 MHz center frequency), which are plotted as post-stimulus time histograms (PSTHs, 1-ms bins) across 100 trials (lower plots in A to C; 32 PSTHs shown for each setup). In A, US focus was at the surface of the intact skin, which is about 4 mm above the nerve. Referring to the pressure profile in Supplementary Fig. S1, the pressure at the nerve in A was approximately 60%, 80%, and 55% of that at the focus, for 0.22, 0.52, and 1 MHz transducer, respectively. In B and C, US focus was at the nerve, which is 1 mm below the plastic cone of the transducer. In (C), the total agar thickness is approximately 2.5 mm. (D) Diagram of preparation for recording multi-unit activity from SSC with a 32-site electrode array. (E) Diagram of preparation for recording compound action potentials (CAPs) in response to electrical stimulation (ES) of the foot, ES of the nerve, and US stimulation of the nerve. (F–H) Examples of the averaged CAPs in response to 100 trials of biphasic ES (205 µs/phase, 0.1 mA) of the sciatic nerve with platinum-iridium wire electrodes (F), biphasic ES (205 µs/phase, 2.82 mA) of the foot with stainless steel needle electrodes (G), and US stimulation (1.3 MPa, single pulse, 1 ms PD, 0.5 s TD, 0.52 MHz center frequency) of the sciatic nerve (H). Single trial CAPs were also plotted as red curves. Representative examples of PSTHs are shown in the right column. The onset time of ES or US stimulation was at zero (black dotted lines in F to H). Electrical artifacts are observed in the CAPs (black arrows in F and G).