Transcranial Focused Ultrasound for Noninvasive Neuromodulation of the Visual Cortex
Gengxi Lu, Xuejun Qian, Johnny Castillo, Runze Li, Laiming Jiang, Haotian Lu, K. Kirk Shung, Mark S. Humayun, Biju B. Thomas, Qifa Zhou
IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 2021, 68, 21-28 · 10.1109/tuffc.2020.3005670
Abstract
Currently, blindness cannot be cured and patients' living quality can be compromised severely. Ultrasonic (US) neuromodulation is a promising technology for the development of noninvasive cortical visual prosthesis. We investigated the feasibility of transcranial focused ultrasound (tFUS) for noninvasive stimulation of the visual cortex (VC) to develop improved visual prosthesis. tFUS was used to successfully evoke neural activities in the VC of both normal and retinal degenerate (RD) blind rats. Our results showed that blind rats showed more robust responses to ultrasound stimulation when compared with normal rats. ( , two-sample t-test). Three different types of ultrasound waveforms were used in the three experimental groups. Different types of cortical activities were observed when different US waveforms were used. In all rats, when stimulated with continuous ultrasound waves, only short-duration responses were observed at "US on and off" time points. In comparison, pulsed waves (PWs) evoked longer low-frequency responses. Testing different parameters of PWs showed that a pulse repetition frequency higher than 100 Hz is required to obtain the low-frequency responses. Based on the observed cortical activities, we inferred that acoustic radiation force (ARF) is the predominant physical mechanism of ultrasound neuromodulation.
Abstract via europepmc.
Exposures
Exposure 1: tFUS to visual cortex, continuous and pulsed waveform groups
Target: primary visual cortex — “visual cortex (VC), area 17”
Device: custom-built
| Waveform | continuous, pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 1, 0.5, 1, 2, 5swept | ✓✓✓ |
| Pulse repetition frequency (Hz) | 500, 500, 333.3, 200, 100swept | ✓✓✓ |
| Duty cycle (%) | 25, 33.3, 40, 50swept | ✓✓✓ |
| Sonication duration (s) | 0.002, 0.015, 0.03swept | ✓✓✓ |
| Free-field pressure (kPa) | 3,740 | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | 115.8 | ✓✓✓ |
| 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 |
Three waveform groups were tested at the same amplitude: group 1, a single 15-ms continuous wave (CW) tone burst following a 6-s rest; group 2, two 2-ms CW tone bursts 20 ms apart, following a 6-s rest; group 3, pulsed waves with five PRF/pulse-width combinations (500 Hz/1 ms, 500 Hz/0.5 ms, 333.3 Hz/1 ms, 200 Hz/2 ms, 100 Hz/5 ms pulse), each delivered for 30 ms following a 6-s rest. During control recordings the transducer was aimed away from the brain with ultrasound still on.
Consistency checks: intensity pressure inconsistent free field.
Flags from extraction
exposures[0].timing.waveform— the single target/frequency exposure combines continuous-wave (groups 1-2: 15 ms and 2x2 ms tone bursts) and pulsed (group 3: five PRF/pulse-width combinations) sub-protocols, per the one-exposure-per-target-frequency rule; pulse_duration_ms/PRF/duty_cycle_pct lists reflect only the pulsed (group 3) sub-protocol, while sonication_duration_s lists durations from all three groups.exposures[0].free_field.pressure_kpa— reported as a peak-to-peak amplitude (3.74 MPa), not a peak-negative or peak-positive pressure; recorded as stated.exposures[0].in_situ— the paper only estimates skull transmission loss qualitatively, citing an external reference for a 0.5-0.7 transmission factor to argue the mechanical index would remain within FDA limits after skull attenuation; no in-brain pressure/intensity value in kPa or W/cm2 is given by this study itself.auditory_control— the paper describes a separate control experiment stimulating the auditory cortex directly (finding no VC response) rather than a standard masking/sham auditory control for the main experiment.n_sessions_per_subject— the paper describes one continuous recording procedure (baseline, light stimulation, ultrasound stimulation, control recording) per animal but never explicitly states a session count.