Modulation of cardio-respiratory activity in mice via transcranial focused ultrasound
Ethan V. Bendau, Erica P. McCune, Samuel G. Blackman, Hermes A.S. Kamimura, Christian Aurup, Elisa E. Konofagou
Ultrasound in Medicine & Biology 2024, 50, 332-340 · 10.1016/j.ultrasmedbio.2023.11.003
Abstract
Objective The objective of this study was to investigate the effect of FUS on autonomic nervous system activity, including heart and respiratory rates, and to separate the thermal modulation from combined thermal and mechanical FUS effects. Methods The thalamus and hypothalamus of wild-type mice were sonicated with a continuous-wave, 2 MHz FUS transducer at pressures of 425 and 850 kPa for 60 seconds. Cardiac and respiratory rates were monitored as signs of autonomic nervous activity. FUS-induced changes in autonomic activity were compared to FUS targeted to a spatially-distant motor region and to laser-induced heating. Results FUS delivered to the primary target over the thalamus and hypothalamus at 850 kPa reversibly increased the respiratory rate by 6.5±3.2 breaths per minute and decreased the heart rate by 3.2±1.8 beats per minute. No significant changes occurred in this region at 425 kPa or when targeting the motor regions at 850 kPa. Laser heating with the same temperature rise profile produced by 850 kPa sonication resulted in cardiorespiratory modulation similar to that of FUS. Conclusions FUS is capable of reversibly and non-invasively modulating cardiorespiratory activity in mice. Localized changes in temperature may constitute the main cause for this activity, though further investigation is warranted into the distinct and complementary mechanisms of mechanically- and thermally-induced FUS neuromodulation. Close monitoring of vital signs during FUS neuromodulation may be warranted to monitor systemic responses to stimulation.
Abstract via europepmc.
Exposures
Exposure 1: Location I (thalamus/hypothalamus)
Target: thalamus, hypothalamus — “thalamus and hypothalamus (Location I: +2 mm posterior, +2 mm lateral to lambda)”
Device: IGT / Imasonic · Imasonic SAS ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 2,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | 100 | ✓? |
| Sonication duration (s) | 60 | ✓✓✓ |
| Free-field pressure (kPa) | 425, 850swept | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 300, 600swept | ✓✓✓ |
| In-situ Isppa (W/cm²) | 2.5, 10swept | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | not reported |
The target location was sonicated for 60 seconds with 60 seconds between trials for up to 15 trials per mouse; each mouse underwent one sonication session.
Exposure 2: Location II (motor cortex/caudate putamen)
Target: primary motor cortex, dorsal striatum — “primary motor cortex (M1) and caudate putamen (Location II: +5.2 mm posterior, +1.5 mm lateral to lambda)”
Device: IGT / Imasonic · Imasonic SAS ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 2,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | 100 | ✓? |
| Sonication duration (s) | 60 | ✓✓✓ |
| Free-field pressure (kPa) | 850swept | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 600swept | ✓✓✓ |
| In-situ Isppa (W/cm²) | 10swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
The target location was sonicated for 60 seconds with 60 seconds between trials for up to 15 trials per mouse; each mouse underwent one sonication session.
Flags from extraction
sham_type— A 'sham condition' is referenced in the results/figures (e.g., 'In the sham condition, changes in cardiac and respiratory rate...') but its mechanism is not described in the Methods.exposures[1].free_field.pressure_kpa— Only 850 kPa (with its associated derated values) is explicitly restated for Location II; the same derating/intensity figures given for Location I are assumed to apply since the paper does not repeat separate derated values for Location II.exposures[0].in_situ.isppa_w_cm2— The 425 kPa entry's intensity unit in the source text is garbled ('2.5 W=cm2 I') without an explicit ISPPA subscript, unlike the 850 kPa entry which explicitly states I_SPPA; both are recorded as ISPPA by parallel structure.blinding— The paper states data was 'processed blindly' (blinded analysis of cardiac/respiratory extraction), which is recorded as single blinding; this does not necessarily reflect blinding of stimulus delivery.