Ketamine Inhibits Ultrasound Stimulation-Induced Neuromodulation by Blocking Cortical Neuron Activity
Sungmin Han, Minkyung Kim, Hyungmin Kim, Hyunjoon Shin, Inchan Youn
Ultrasound in Medicine & Biology 2018 · 10.1016/j.ultrasmedbio.2017.11.008
Abstract
Ultrasound (US) can be used to noninvasively stimulate brain activity. However, reproducible motor responses evoked by US are only elicited when the animal is in a light state of anesthesia. The present study investigated the effects of ketamine on US-induced motor responses and cortical neuronal activity. US was applied to the motor cortex of mice, and motor responses were evaluated based on robustness scores. Cortical neuronal activity was observed by fluorescence calcium imaging. US-induced motor responses were inhibited more than 20 min after ketamine injection, and US-triggered Ca 2+ transients in cortical neurons were effectively blocked by ketamine. Our results indicate that ketamine suppresses US-triggered Ca 2+ transients in cortical neurons and, therefore, inhibits US-induced motor responses in a deep anesthetic state.
Abstract via europepmc.
Exposures
Exposure 1: Motor cortex sonication (mice, in vivo)
Target: primary motor cortex — “motor cortex”
Device: other named manufacturer · EofE Ultrasonics Co., Ltd ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 350 | ✓✓✓ |
| Pulse duration (ms) | 0.23 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,500 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 34.5% | ⚑ |
| Sonication duration (s) | 0.0667 | ✓✓✓ |
| Free-field pressure (kPa) | 60, 690swept | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | ⚑ |
| Free-field Ispta (W/cm²) | 1.16, 13.55swept | ✓✓✓ |
| 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 |
Two function generators were serially connected to generate bursts of pulsed waves, where the first function generator regulated the PRF, the SD and the inter-stimulus interval (ISI). Sonication was induced with 350-kHz FF, 1.5-kHz PRF, 0.23-ms TBD, and 66.67-ms SD; the robustness scores were evaluated for AIs varied 1.16-13.55 W/cm2 (0.06-0.69 MPa), and a fixed AI of 3.46 W/cm2 was used for the onset-time and histologic safety experiments.
Exposure 2: Cultured cortical neurons (in vitro)
Target: cultured neurons — “cultured cortical neurons”
Device: other named manufacturer · EofE Ultrasonics Co., Ltd ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 350 | ✓✓✓ |
| Pulse duration (ms) | 0.23 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,500 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 34.5% | |
| Sonication duration (s) | 0.0667 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.056 | ✓✓✓ |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable |
Sonication was induced with the same parameters described earlier (350-kHz FF, 1.5-kHz PRF, 0.23-ms TBD, 66.67-ms SD) and the AI was set to 56 mW/cm2, measured in the degassed water; fluorescence was recorded for 3 min with US applied 1 min after recording started.
Flags from extraction
n_subjects— Paper reports separate mouse cohorts for different sub-experiments (8, 6, 17, and 3 mice) without stating an overall total exposed to ultrasound; unclear whether cohorts overlap.exposures[0].free_field.isppa_w_cm2— The 1.16-13.55 W/cm2 range (robustness-score sweep) and the fixed 3.46 W/cm2 value (used for onset-time and histology experiments) are combined in one list; 3.46 W/cm2 has no separately stated pressure equivalent.exposures[*].free_field— Domain assigned as free_field because the Methods state AI/pressure values were measured via hydrophone in a degassed water tank (and the in vitro AI is explicitly stated as measured in degassed water); the paper does not label every individual number with a domain.exposures[0].timing.duty_cycle_pct— Not stated as a percentage in the text; not computed from pulse duration and PRF per instructions.