Temporal Neuromodulation of Retinal Ganglion Cells by Low-Frequency Focused Ultrasound Stimulation
Qiuju Jiang, Guofeng Li, Huixia Zhao, Wenlong Sheng, Lan Yue, Min Su, Shijun Weng, Leanne Lai-Hang Chan, Qifa Zhou, Mark S. Humayun, Weibao Qiu, Hairong Zheng
IEEE Transactions on Neural Systems and Rehabilitation Engineering 2018 · 10.1109/tnsre.2018.2821194
Abstract
Significant progress has been made recently in treating neurological blindness using implantable visual prostheses. However, implantable medical devices are highly invasive and subject to many safety, efficacy, and cost issues. The discovery that ultrasound (US) may be useful as a noninvasive neuromodulation tool has aroused great interest in the field of acoustic retinal prostheses (ARPs). We have investigated the responsiveness of rat retinal ganglion cells (RGCs) to low-frequency focused US stimulation (LFUS) at 2.25 MHz and characterized the neurophysiological properties of US responses by performing in vitro multielectrode array recordings. The results show that LFUS can reliably activate RGCs. The US-induced responses did not correspond to the standard light responses and varied greatly among cell types. Moreover, dual-peak responses to US stimulation were observed that have not been reported previously. The temporal response properties of RGCs, including their latency, firing rate, and response type, were modulated by the acoustic intensity. These findings suggest the presence of a temporal neuromodulation effect of LFUS and potentially open a new avenue in the development of ARP.
Abstract via europepmc.
Exposures
Exposure 1: 2.25 MHz focused US on isolated rat retina
Target: retinal explant, retina — “rat retinal ganglion cells (RGCs)”
Device: other named manufacturer · Valpey Fisher Corporation · IL0206HP ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 2,250 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 50% | ⚑ |
| Sonication duration (s) | 0.4 | ✓✓✓ |
| Free-field pressure (kPa) | 331 | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.28, 13.16swept | ✓✓✓ |
| 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 |
Pulsed mode: PRF 1 kHz, tone burst duration 0.5 ms, sonication duration 400 ms, interstimulus interval 2 s; 15 stimulus trains per experiment with a 3 min pause between experiments. Intensity varied by function generator voltage.
Flags from extraction
exposures[0].unspecified_domain.ispta_w_cm2— Intensity was varied; the paper gives individual values (threshold 0.28 W/cm2, 12.84 W/cm2 in Fig 5, saturation around 12.84 to 13.16 W/cm2), not a stated sweep range. Two-element list is the threshold and the upper value; quote carries only the upper value. Ispta was calculated from pressure and scaled by 46.34% for the filter membrane.exposures[0].free_field.pressure_kpa— Peak pressure 331 kPa is from a hydrophone scan in a water tank, not explicitly tied to the stimulation settings; the filter membrane attenuated peak pressure (38 vs 82 kPa).exposures[0].timing.duty_cycle_pct— Duty cycle not stated.exposures[0].device.family— Valpey Fisher is a named maker not in the list; mapped to other_manufacturer.