Investigating the impact of skull vibrations on motor responses to focused ultrasound neuromodulation in small rodents and methods to mitigate them
Jake W Hesselink, Chris Krasnichuk, Amine Benaceur, Aidan Johnson, Siyun Li, Zelma H T Kiss, Samuel Pichardo
Physics in Medicine & Biology 2023 · 10.1088/1361-6560/acda0c
Abstract
Objective . Focused ultrasound (FUS) neuromodulation non-invasively alters brain activity, likely via acoustic radiation force with dynamics of the pulse repetition frequency (PRF). PRF impacts neuromodulation as well as indirect auditory activation, a confound linked to skull vibrations. This study aimed to minimize these vibrations, by adjusting and randomizing PRF, and determine their impact on FUS-induced motor activity. We hypothesized that: the skull would vibrate most at a specific PRF; randomizing PRF would reduce skull vibrations without affecting motor responses; and FUS would yield motor activity while actuator-induced skull vibrations would not. Approach . Three objectives were studied in parallel using C57Bl/6 mice ( n = number of mice used per objective). First, skull vibration amplitude, measured as a percentage of maximum amplitude per treatment, was recorded via contact microphone over a range of PRFs to assess the PRF-dependency of skull vibrations ( n = 19). Vibrations were then compared between random and fixed PRFs ( n = 15). Lastly, motor responses were compared between fixed 1.5 kHz PRF FUS, random PRF FUS, air-puff stimulation, sham stimulation, and vibration induction via piezoelectric actuator ( n = 30). Main Results. The study found amplitude peaked at 1.51 kHz (88.1 ± 11.5%), significantly higher than at 0.54 kHz (75.5 ± 15.1%; p = 0.0149). Random PRF reduced amplitude by 4.2% ( p = 0.0181). Motor response rates to actuator-induced skull vibrations at the PRF (5.73 ± 6.96%) and its third harmonic (22.9 ± 22.7%) were not significantly different than sham (14.1 ± 11.6%), but lower than FUS (70.2 ± 16.3%; p Significance . Based on these results, PRF near 0.5 kHz may best avoid skull vibrations, while random PRF could be utilized to slightly reduce vibration amplitude. The results also suggested that skull vibrations likely do not significantly impact motor responses to FUS neuromodulation.
Abstract via europepmc.
Exposures
Exposure 1: FUS to right motor cortex, PRF varied
Target: primary motor cortex — “motor cortex (M1), 1.78 mm right, 0.80 mm anterior, 1.33 mm ventral to bregma”
Device: other named manufacturer · FUS Instruments · RK-50 ✓
| Waveform | pulsed, other_patterned | |
|---|---|---|
| Fundamental frequency (kHz) | 476.5 | ✓✓✓ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | 420, 4,200swept | ✓✓✓⚑ |
| Duty cycle (%) | 31.5 | ✓✓✓ |
| Sonication duration (s) | 0.08 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 12.6 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 3.97 | ✓✓✓⚑ |
| 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 |
80 ms stimulations at 31.5% duty cycle, PRF fixed at 1.5 kHz, randomised about 1.5 kHz (0.42 to 4.2 kHz), or fixed at 0.54 or 2.52 kHz in five animals; five stimulations per treatment under light isoflurane (0.2%). Pulse duration varies with PRF at constant duty cycle.
Flags from extraction
exposures[0].timing.pulse_repetition_frequency_hz— PRF is a sweep of ten logarithmic steps from 0.42 to 4.2 kHz for the vibration objective, 1.5 kHz fixed or random for the motor trials, plus 0.54 and 2.52 kHz in five animals; recorded as the range.exposures[0].free_field.ispta_w_cm2— Ispta 3.97 W/cm2 is stated as derived from Isppa and the 31.5% duty cycle, not measured separately.n_subjects— 32 mice were used; two were sacrificed prematurely, 30 contributed motor data; 19 and 15 mice for the vibration objectives.sham_type— Sham: no power supplied to the transducer. Also a piezoelectric actuator and air-puff comparison, which are not exposures.randomised— Condition order was pseudo-random within groupings.