Visuomotor Transformations Are Modulated by Focused Ultrasound over Frontal Eye Field
Kaleb A. Lowe, Wolf Zinke, M. Anthony Phipps, Josh Cosman, Micala Maddox, Jeffrey D. Schall, Charles F. Caskey
Ultrasound in Medicine & Biology 2021, 47, 679-692 · 10.1016/j.ultrasmedbio.2020.11.022
Abstract
Neuromodulation with focused ultrasound (FUS) is being widely explored as a non-invasive tool to stimulate focal brain regions because of its superior spatial resolution and coverage compared with other neuromodulation methods. The precise effects of FUS stimulation on specific regions of the brain are not yet fully understood. Here, we characterized the behavioral effects of FUS stimulation directly applied through a craniotomy over the macaque frontal eye field (FEF). In macaque monkeys making directed eye movements to perform visual search tasks with direct or arbitrary responses, focused ultrasound was applied through a craniotomy over the FEF. Saccade response times (RTs) and error rates were determined for trials without or with FUS stimulation with pulses at a peak negative pressure of either 250 or 425 kPa. Both RTs and error rates were affected by FUS. Responses toward a target located contralateral to the FUS stimulation were approximately 3 ms slower in the presence of FUS in both monkeys studied, while only one exhibited a slowing of responses for ipsilateral targets. Error rates were lower in one monkey in this study. In another search task requiring making eye movements toward a target (pro-saccades) or in the opposite direction (anti-saccades), the RT for pro-saccades increased in the presence of FUS stimulation. Our results indicate the effectiveness of FUS to modulate saccadic responses when stimulating FEF in awake, behaving non-human primates.
Abstract via europepmc.
Exposures
Exposure 1: FUS to frontal eye field (FEF) through craniotomy, low and high intensity
Target: frontal eye field — “frontal eye field (FEF)”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.25 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 2,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| Free-field pressure (kPa) | 250, 425swept | ✓✓✓⚑ |
|---|---|---|
| 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 |
A 300-ms FUS block (125 cycles pulsed at 2 kHz within the block, 50% duty cycle) was delivered through a craniotomy directly onto the dura over FEF, centered on visual array onset. In monkeys Ga and He, FUS/no-FUS blocks of 10 min alternated, with low (250 kPa) and high (425 kPa) intensity used in different halves of each session (order alternated between sessions, ~3.5 alternations per intensity per session). In monkey Da, FUS was delivered on a randomly selected 50% of trials.
Flags from extraction
exposures[0].timing.pulse_duration_ms— pulse duration (0.25 ms) computed from the paper's own stated 125 cycles at the 500-kHz fundamental frequency, consistent with the stated 50% duty cycle at 2 kHz PRF; resolved via the sanctioned cycles/frequency conversion.exposures[0].free_field.pressure_kpa— pressures were calibrated in a water tank (free field) using a coupling cone geometry matched to the craniotomy/dura contact (no intervening skull); the paper does not explicitly restate these as in-brain (in_situ) values even though no skull attenuation would be expected.randomised— for monkeys Ga and He, FUS/no-FUS blocks and intensity order were alternated (not stated as randomised); only monkey Da received trial-wise random FUS delivery (50% of trials); overall randomisation status is mixed/unclear.n_sessions_per_subject— session counts differ by animal: Ga and He each performed 14 sessions of the shape-singleton task, while Da performed 20 sessions of the pro-/anti-saccade task.