Effective Parameters for Ultrasound-Induced In Vivo Neurostimulation
Randy L. King, Julian R. Brown, William T. Newsome, Kim Butts Pauly
Ultrasound in Medicine & Biology 2013, 39, 312-331 · 10.1016/j.ultrasmedbio.2012.09.009
Abstract
Ultrasound-induced neurostimulation has recently gained increasing attention, but little is known about the mechanisms by which it affects neural activity or about the range of acoustic parameters and stimulation protocols that elicit responses. We have established conditions for transcranial stimulation of the nervous system in vivo, using the mouse somatomotor response. We report that (1) continuous-wave stimuli are as effective as or more effective than pulsed stimuli in eliciting responses, and responses are elicited with stimulus onset rather than stimulus offset; (2) stimulation success increases as a function of both acoustic intensity and acoustic duration; (3) interactions of intensity and duration suggest that successful stimulation results from the integration of stimulus amplitude over a time interval of 50 to 150 ms; and (4) the motor response elicited appears to be an all-or-nothing phenomenon, meaning stronger stimulus intensities and durations increase the probability of a motor response without affecting the duration or strength of the response.
Abstract via europepmc.
Exposures
Exposure 1: Continuous-wave and pulsed transcranial ultrasound stimulation of mouse motor cortex/basal ganglia at 500 kHz
Target: motor cortex, basal ganglia — “the basal ganglia and the motor cortex”
Device: Olympus / Panametrics · Olympus · V301 ✓
| Waveform | continuous, pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.2 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 11, 3,000swept | ✓✓✓ |
| Duty cycle (%) | 2, 30, 60swept | ✓✓✓⚑ |
| Sonication duration (s) | 0.02, 0.04, 0.08, 0.16, 0.24, 0.32, 0.48swept | ✓✓✓ |
| Free-field pressure (kPa) | 30, 1,110swept | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 0.01, 79.02swept | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | not reported | ⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
All experiments were conducted using continuous-wave ultrasound sonications at the center frequency of the transducer (500 kHz), unless otherwise noted; sonication durations varied from 20 to 480 ms, and intensities ranged from 0.01 to 79.02 W/cm2 (0.03 to 1.11 MPa). For pulsed ultrasound, the pulse repetition frequency was held constant at 1.5 kHz with 100 cycles per pulse (30% duty cycle) in the CW-vs-pulsed comparison, and separately varied between 11 and 3000 Hz (100 cycles per pulse, 120 pulses per train) in the PRF experiment. The specified sonication conditions were generated in a pseudo-random sequence, with a minimum interval between sonications of 5 s.
Exposure 2: Frequency-response characterization at 250 kHz
Target: motor cortex, basal ganglia — “the basal ganglia and the motor cortex”
Device: Olympus / Panametrics · Olympus · V301 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.16 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| 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 |
Continuous-wave sonications of 40,000 cycles were delivered at this frequency using 3 driving voltages (75, 150 and 300 mVpp) in blocks, to test how success rate depended on carrier frequency; the resulting acoustic intensities are shown only in Figure 10, not stated numerically in the text.
Exposure 3: Frequency-response characterization at 300 kHz
Target: motor cortex, basal ganglia — “the basal ganglia and the motor cortex”
Device: Olympus / Panametrics · Olympus · V301 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 300 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.133 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| 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 |
Continuous-wave sonications of 40,000 cycles were delivered at this frequency using 3 driving voltages (75, 150 and 300 mVpp) in blocks, to test how success rate depended on carrier frequency; the resulting acoustic intensities are shown only in Figure 10, not stated numerically in the text.
Exposure 4: Frequency-response characterization at 350 kHz
Target: motor cortex, basal ganglia — “the basal ganglia and the motor cortex”
Device: Olympus / Panametrics · Olympus · V301 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 350 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.114 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| 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 |
Continuous-wave sonications of 40,000 cycles were delivered at this frequency using 3 driving voltages (75, 150 and 300 mVpp) in blocks, to test how success rate depended on carrier frequency; the resulting acoustic intensities are shown only in Figure 10, not stated numerically in the text.
Exposure 5: Frequency-response characterization at 400 kHz
Target: motor cortex, basal ganglia — “the basal ganglia and the motor cortex”
Device: Olympus / Panametrics · Olympus · V301 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 400 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.1 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| 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 |
Continuous-wave sonications of 40,000 cycles were delivered at this frequency using 3 driving voltages (75, 150 and 300 mVpp) in blocks, to test how success rate depended on carrier frequency; the resulting acoustic intensities are shown only in Figure 10, not stated numerically in the text.
Exposure 6: Frequency-response characterization at 450 kHz
Target: motor cortex, basal ganglia — “the basal ganglia and the motor cortex”
Device: Olympus / Panametrics · Olympus · V301 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 450 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.0889 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| 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 |
Continuous-wave sonications of 40,000 cycles were delivered at this frequency using 3 driving voltages (75, 150 and 300 mVpp) in blocks, to test how success rate depended on carrier frequency; the resulting acoustic intensities are shown only in Figure 10, not stated numerically in the text.
Exposure 7: Frequency-response characterization at 550 kHz
Target: motor cortex, basal ganglia — “the basal ganglia and the motor cortex”
Device: Olympus / Panametrics · Olympus · V301 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 550 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.0727 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| 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 |
Continuous-wave sonications of 40,000 cycles were delivered at this frequency using 3 driving voltages (75, 150 and 300 mVpp) in blocks, to test how success rate depended on carrier frequency; the resulting acoustic intensities are shown only in Figure 10, not stated numerically in the text.
Exposure 8: Frequency-response characterization at 600 kHz
Target: motor cortex, basal ganglia — “the basal ganglia and the motor cortex”
Device: Olympus / Panametrics · Olympus · V301 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 600 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.0667 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| 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 |
Continuous-wave sonications of 40,000 cycles were delivered at this frequency using 3 driving voltages (75, 150 and 300 mVpp) in blocks, to test how success rate depended on carrier frequency; the resulting acoustic intensities are shown only in Figure 10, not stated numerically in the text.
Flags from extraction
exposures[0].timing.pulse_duration_ms— Pulse duration (0.2 ms) computed from stated cycles per pulse (100) divided by fundamental frequency (500 kHz); an explicitly permitted unit conversion, but applies only to the pulsed sub-experiments within this exposure, not the continuous-wave sub-experiments also included here.exposures[0].timing.duty_cycle_pct— This exposure mixes continuous-wave (duty cycle effectively 100 percent, but not stated as a number in text) and pulsed sub-experiments; only the explicitly stated pulsed duty-cycle values are listed.exposures[0].free_field.isppa_w_cm2— The text does not specify whether the 0.01-79.02 W/cm2 range is spatial-peak pulse-average or spatial-peak temporal-average intensity; for the CW portion these are equal, but the exposure also includes pulsed sub-experiments where they would differ.exposures[0].in_situ.pressure_kpa— 0.12 MPa is from a separate ex vivo mouse-skull hydrophone calibration scan used to justify ignoring skull effects, not necessarily the peak pressure delivered during any specific behavioural trial; domain correspondence to the free-field range is uncertain.exposures[1-7]— Acoustic intensities for the 250-450, 550 and 600 kHz frequency-response experiment are shown only in Figure 10, not given as numbers in the main text, so are recorded as not_reported.auditory_control— The paper's coupling/uncoupling control tests for an airborne-sound confound but does not match any listed auditory_control category precisely; categorized as other.n_sessions_per_subject— Not stated as a single value; anesthesia-level and other sub-experiments describe blocks/visits per animal but no consistent session count is given.