Closed-Loop Transcranial Ultrasound Stimulation for Real-Time Non-invasive Neuromodulation in vivo
Huifang Yang, Yi Yuan, Xingran Wang, Xin Li
Frontiers in Neuroscience 2020, 14 · 10.3389/fnins.2020.00445
Abstract
The closed-loop brain stimulation technique plays a key role in neural network information processing and therapies of neurological diseases. Transcranial ultrasound stimulation (TUS) is an established neuromodulation method for the neural oscillation in animals or human. All available TUS systems provide brain stimulation in an open-loop pattern. In this study, we developed a closed-loop transcranial ultrasound stimulation (CLTUS) system for real-time non-invasive neuromodulation in vivo . We used the CLTUS system to modulate the neural activities of the hippocampus of a wild-type mouse based on the phase of the theta rhythm recorded at the ultrasound-targeted location. In addition, we modulated the hippocampus of a temporal lobe epilepsy (TLE) mouse. The ultrasound stimulation increased the absolute power and reduced the relative power of the theta rhythm, which were independent of the specific phase of the theta rhythm. Compared with those of a sham stimulation, the latency of epileptic seizures was significantly increased, while the epileptic seizure duration was significantly decreased under the CLTUS. The above results indicate that the CLTUS can be used to not only modulate the neural oscillation through the theta-phase-specific manipulation of the hippocampus but also effectively inhibit the seizure of a TLE mouse in time. CLTUS has large application potentials for the understanding of the causal relationship of neural circuits as well as for timely, effective, and non-invasive therapies of neurological diseases such as epilepsy and Parkinson's disease.
Abstract via europepmc.
Exposures
Exposure 1: CLTUS of hippocampal CA1, modulation of theta rhythm
Target: CA1 — “hippocampal CA1 region”
Device: Olympus / Panametrics · Olympus, United States · V301-SU ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.4 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 40 | ✓✓✓ |
| Sonication duration (s) | 0.4 | ✓✓✓ |
| 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) | 230 | ✓✓✓ |
| Isppa, domain unspecified (W/cm²) | 1.75 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 0.7 | ✓✓✓⚑ |
CLTUS was used to modulate the neural activities based on the theta phase locally recorded by using a recording electrode implanted in the mouse hippocampus CA1. In a sham stimulation (sham-stim), we turned of the amplifier, while the other experimental procedures were the same as those for the CLTUS. The CLTUS and sham-stim were performed in a random order.
Exposure 2: CLTUS of hippocampal CA3, inhibition of TLE seizures
Target: CA3 — “CA3 area”
Device: Olympus / Panametrics · Olympus, United States · V301-SU ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.1 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 500 | ✓✓✓ |
| Duty cycle (%) | 5 | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓ |
| 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) | 230 | ✓✓✓ |
| Isppa, domain unspecified (W/cm²) | 1.75 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 0.0665 | ✓✓✓ |
Kainic acid (KA) was unilaterally microinfused into the CA3 area to generate a temporal lobe epilepsy (TLE) model; a tungsten microelectrode was inserted into the CA3 region 2 h after generation of the TLE model. We recorded the data of TLE for 60 min and simultaneously carried out CLTUS on the TLE mouse model. In order to achieve self-control, we used the same animal for CLTUS and sham-stim.
Flags from extraction
exposures[0].unspecified_domain.ispta_w_cm2— Methods states Ispta = 700 mW/cm2 for the neural-oscillation (CA1) exposure, but the Discussion states 'The ultrasound intensities (Ispta) used in our experiments were ∼533 mW/cm2 (for the modulation of the neural oscillation)'; the two values disagree within the same paper. The Methods value (700 mW/cm2) is recorded here.randomised— Randomisation statement ('The CLTUS and sham-stim were performed in a random order') applies explicitly to the CA3/TLE self-control sub-experiment; it is unclear whether it also applies to the CA1 phase-locked stimulation sub-experiment.