Non-Invasive Hybrid Ultrasound Stimulation of Visual Cortex In Vivo
Chen Gong, Runze Li, Gengxi Lu, Jie Ji, Yushun Zeng, Jiawen Chen, Chifeng Chang, Junhang Zhang, Lily Xia, Deepthi S. Rajendran Nair, Biju B. Thomas, Brian J. Song, Mark S. Humayun, Qifa Zhou
Bioengineering 2023 · 10.3390/bioengineering10050577
Abstract
The optic nerve is the second cranial nerve (CN II) that connects and transmits visual information between the retina and the brain. Severe damage to the optic nerve often leads to distorted vision, vision loss, and even blindness. Such damage can be caused by various types of degenerative diseases, such as glaucoma and traumatic optic neuropathy, and result in an impaired visual pathway. To date, researchers have not found a viable therapeutic method to restore the impaired visual pathway; however, in this paper, a newly synthesized model is proposed to bypass the damaged portion of the visual pathway and set up a direct connection between a stimulated visual input and the visual cortex (VC) using Low-frequency Ring-transducer Ultrasound Stimulation (LRUS). In this study, by utilizing and integrating various advanced ultrasonic and neurological technologies, the following advantages are achieved by the proposed LRUS model: 1. This is a non-invasive procedure that uses enhanced sound field intensity to overcome the loss of ultrasound signal due to the blockage of the skull. 2. The simulated visual signal generated by LRUS in the visual-cortex-elicited neuronal response in the visual cortex is comparable to light stimulation of the retina. The result was confirmed by a combination of real-time electrophysiology and fiber photometry. 3. VC showed a faster response rate under LRUS than light stimulation through the retina. These results suggest a potential non-invasive therapeutic method for restoring vision in optic-nerve-impaired patients using ultrasound stimulation (US).
Abstract via europepmc.
Exposures
Exposure 1: 3.6 MHz ring transducer to rat visual cortex, 30 ms and 60 ms stimulation
Target: primary visual cortex — “visual cortex (VC)”
Device: not reported
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 3,600 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.03, 0.06swept | ✓✓✓⚑ |
| Free-field pressure (kPa) | 3,600 | ✓✓✓⚑ |
|---|---|---|
| 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 |
3.6 MHz sine wave in burst mode, stimulation time 30 ms (cycle = 107 k) and 60 ms (cycle = 214 k), interval 5 s; the methods also mention a '250 ms Burst cycle' for the field measurements. Light stimulation (flash <1 ms) delivered for comparison.
Flags from extraction
exposures[0].free_field.pressure_kpa— Peak-to-peak 3.6 MPa (MI 2.6) in free field; skull transmission 0.5-0.6 and MI 1.3-1.6 through skull given but no in situ pressure value.exposures[0].timing.sonication_duration_s— Source text is garbled by overlapping OCR; 30 ms and 60 ms single bursts per trial, treated as continuous. '250 ms Burst cycle' in field-measurement methods not reconciled.exposures[0].device.family— No transducer maker or builder named ('PZT ring transducer').sham_type— Only control is transducer and electrodes placed in water to check for electrical and vibration artefact; no sham US arm in vivo.auditory_control— Authors argue against auditory route from latency and V1-restricted GCaMP expression; no control experiment or masking.exposures[0].target— Methods describe a cranial window over the visual cortex while results say non-invasive through the skull; skull-in-path hydrophone measurements were made.