Noninvasive Ultrasonic Neuromodulation in Freely Moving Mice
Guofeng Li, Weibao Qiu, Zhiqiang Zhang, Qiuju Jiang, Min Su, Ruilin Cai, Yongchuan Li, Feiyan Cai, Zhiting Deng, Di Xu, Huailing Zhang, Hairong Zheng
IEEE Transactions on Biomedical Engineering 2019, 66, 217-224 · 10.1109/tbme.2018.2821201
Abstract
Neuromodulation is a fundamental method for obtaining basic information about neuronal circuits for use in treatments for neurological and psychiatric disorders. Ultrasound stimulation has become a promising approach for noninvasively inducing neuromodulation in animals and humans. However, the previous investigations were subject to substantial limitations, due to most of them involving anesthetized and fixed small-animal models. Studies of awake and freely moving animals are needed, but the currently used ultrasound devices are too bulky to be applied to a freely moving animal. This study is the first time to design and fabricate a miniature and lightweight head-mounted ultrasound stimulator for inducing neuromodulation in freely moving mice. The main components of the stimulator include a miniature piezoelectric ceramic, a concave epoxy acoustic lens, and housing and connection components. The device was able to induce action potentials recorded in situ and evoke head-turning behaviors by stimulating the primary somatosensory cortex barrel field of the mouse. These findings indicate that the proposed method can be used to induce noninvasive neuromodulation in freely moving mice. This novel method could potentially lead to the application of ultrasonic neuromodulation in more-extensive neuroscience investigations.
Abstract via europepmc.
Exposures
Exposure 1: Head-mounted ultrasound stimulation of primary somatosensory cortex barrel field (S1BF) in freely moving mice
Target: primary somatosensory cortex — “primary somatosensory cortex barrel field (S1BF)”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 2,000 | ✓✓✓ |
| Pulse duration (ms) | 0.3 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓⚑ |
| Duty cycle (%) | 30pulse duration × PRF gives 30% | ✓✓✓ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| 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 | |
| Pressure, domain unspecified (kPa) | 1,200 | ✓✓✓ |
| Isppa, domain unspecified (W/cm²) | 46 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 0.7 | ✓✓✓ |
A series of 2-MHz ultrasound stimuli was delivered to each mouse in a 360-s trial for electrophysiology (stimulus repetition period 6 s). For head-turning tests, two head-mounted stimulators (left and right S1BF) delivered the same stimulus parameters alternately every 6 s; control trials used the same procedure but without acoustic coupling gel so no ultrasound entered the brain.
Flags from extraction
exposures[0].timing.pulse_repetition_frequency_hz— PRF converted from the stated pulse repetition period T2 = 1 ms via the paper's own formula PRF = 1/T2, not independent arithmetic.n_sessions_per_subject— US-SPIKE mice received one 360-s recording trial; US-HEAD mice received many alternating stimuli within a single behavioural test session; paper does not define a discrete session count.exposures[0].free_field.pressure_kpa— Values (P0, Isppa, Ispta) given in the Stimulus Parameters/Results section are transducer output values in the acoustic focal region; not explicitly stated as pre- versus post-skull, though a separate ~3 dB skull attenuation is reported elsewhere without being applied to this specific stimulus.