Frequency dependent, reversible focused ultrasound suppression of evoked potentials in the reflex arc in an anesthetized animal
R. H. El Hassan, N. B. Lawand, E. D. Al‐Chaer, M. L. Khraiche
Journal of the Peripheral Nervous System 2022, 27, 271-282 · 10.1111/jns.12512
Abstract
Objective To investigate the potential for noninvasive low frequency, low intensity ultrasound to suppress evoked potentials in the reflex arc neural pathway in anesthetized animal. Material and methods Single unit Electromyographic recordings of gastrocnemius muscle activity were obtained in response to electrical activation of the sciatic nerve, in anesthetized animal, with and without US stimulation. Reflex related potentials were evoked via electrical stimulation and low-intensity, low-frequency ultrasound was applied to the sciatic nerve. Electromyogram (EMG) was recorded from the gastrocnemius muscle and amplitude and area under the curve were analyzed to determine the effect of ultrasound stimulation on potentials in the reflex arc. Thermal imaging was used to assess thermal effects of US stimulation and immunohistochemical was performed post-US stimulation assess potential damage to the nerve. Results Our results show a drop in electromyogram amplitudes as high as 20%, and a drop in areas under the curve as high as 23%, with greater effects at lower frequencies (200 kHz) and lower acoustic intensities. The suppression of EMG scales with the magnitude of the electrical stimuli. Also, our results demonstrated transient reversibility of US suppression and our experiments eliminated thermal effects and mechanical and thermal damage. Conclusion The non-invasiveness of US stimulation and its inhibitory and reversible effects emphasize the potential of US as a therapeutic modality and clinical tool for suppression of neural potentials in the reflex arc such as the case for pain treatments. The study lays the ground for potential applications of US stimulation in pain treatment.
Abstract via europepmc.
Exposures
Exposure 1: 200 kHz continuous-wave US to sciatic nerve
Target: sciatic nerve — “sciatic nerve”
Device: other named manufacturer · Mana Instruments · E1012-SU ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 200 | ✓✓✓ |
| Pulse duration (ms) | not applicable | ⚑ |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | ⚑ |
| Sonication duration (s) | 10 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 9.34, 4.16, 2.58swept | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Electrical stimulation was applied to the sciatic nerve for 20 s to evoke muscle activity, then continuous-wave US was applied simultaneously with electrical stimulation for 10 s, followed by 20 s of electrical stimulation alone to assess recovery. Each of 27 US/electrical parameter combinations plus 3 electrical-only controls was repeated three times in randomized order (90 recordings total per experiment), with 1 min rest between stimulations. During transducer characterization (not necessarily identical to the in-nerve exposure protocol), the transducer was described as operating with a 'burst duration 12 ms'.
Exposure 2: 500 kHz continuous-wave US to sciatic nerve
Target: sciatic nerve — “sciatic nerve”
Device: other named manufacturer · Mana Instruments · E1012-SU ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 10 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 11.1, 6.06, 5.04swept | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Electrical stimulation was applied to the sciatic nerve for 20 s to evoke muscle activity, then continuous-wave US was applied simultaneously with electrical stimulation for 10 s, followed by 20 s of electrical stimulation alone to assess recovery. Each of 27 US/electrical parameter combinations plus 3 electrical-only controls was repeated three times in randomized order (90 recordings total per experiment), with 1 min rest between stimulations. During transducer characterization (not necessarily identical to the in-nerve exposure protocol), the transducer was described as operating with a 'burst duration 12 ms'.
Exposure 3: 700 kHz continuous-wave US to sciatic nerve
Target: sciatic nerve — “sciatic nerve”
Device: other named manufacturer · Mana Instruments · E1012-SU ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 700 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 10 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 17.51, 5.65, 2.83swept | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Electrical stimulation was applied to the sciatic nerve for 20 s to evoke muscle activity, then continuous-wave US was applied simultaneously with electrical stimulation for 10 s, followed by 20 s of electrical stimulation alone to assess recovery. Each of 27 US/electrical parameter combinations plus 3 electrical-only controls was repeated three times in randomized order (90 recordings total per experiment), with 1 min rest between stimulations. During transducer characterization (not necessarily identical to the in-nerve exposure protocol), the transducer was described as operating with a 'burst duration 12 ms'.
Flags from extraction
exposures[0].timing.pulse_duration_ms— Ultrasound characterization text states 'burst duration 12 ms' at 200/500/700 kHz, while the applied nerve-stimulation protocol states continuous-wave US applied for 10 s; unclear whether the 12 ms figure describes internal pulsing of the applied stimulus or is purely a calibration/characterization parameter, so pulse_duration_ms was left null rather than guessed.exposures[0].timing.duty_cycle_pct— Paper states waveform is a continuous sine wave but never gives an explicit duty-cycle percentage; left null rather than assuming 100%.sham_type— No inactive-transducer or sham-US condition was used; the only control condition was electrical stimulation alone (no US), classified here as 'none'.in_situ— Only water-tank (free-field) hydrophone-measured intensities are reported for the applied stimuli; no separate in-situ (derated/simulated/measured-in-tissue) values are given even though US was applied directly to an exposed nerve.