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Low-Intensity Focused Ultrasound Modulates Monkey Visuomotor Behavior

Thomas Deffieux, Youliana Younan, Nicolas Wattiez, Mickael Tanter, Pierre Pouget, Jean-François Aubry

Current Biology 2013, 23, 2430-2433 · 10.1016/j.cub.2013.10.029

nonhuman primatehealthybehaviour

Abstract

In vivo feasibility of using low-intensity focused ultrasound (FUS) to transiently modulate the function of regional brain tissue has been recently tested in anesthetized lagomorphs [1] and rodents [2-4]. Hypothetically, ultrasonic stimulation of the brain possesses several advantages [5]: it does not necessitate surgery or genetic alteration but could ultimately confer spatial resolutions superior to other noninvasive methods. Here, we gauged the ability of noninvasive FUS to causally modulate high-level cognitive behavior. Therefore, we examined how FUS might interfere with prefrontal activity in two awake macaque rhesus monkeys that had been trained to perform an antisaccade (AS) task. We show that ultrasound significantly modulated AS latencies. Such effects proved to be dependent on FUS hemifield of stimulation (relative latency increases most for ipsilateral AS). These results are interpreted in terms of a modulation of saccade inhibition to the contralateral visual field due to the disruption of processing across the frontal eye fields. Our study demonstrates for the first time the feasibility of using FUS stimulation to causally modulate behavior in the awake nonhuman primate brain. This result supports the use of this approach to study brain function. Neurostimulation with ultrasound could be used for exploratory and therapeutic purposes noninvasively, with potentially unprecedented spatial resolution.

Abstract via europepmc.

Speciesrhesus macaque (Macaca mulatta)
Subjects2 animals
Sessions per subject10, 12swept
Randomisedyes
Blindingnot reported
Sham / controlactive control site, inactive transducer
Auditory controlnot reported
Readout timingonline
Anaesthesiaawake
ReadoutsbehaviourAntisaccade/prosaccade task: saccade latency, error rate, amplitude, peak velocity and skewness measured via infrared eye tracking
Direction of effectinhibitoryIpsilateral antisaccade latencies were significantly slowed by FUS to the left FEF (monkey Y and L), with a marginal increase in contralateral error rate for one monkey; no significant effect on contralateral latencies, saccade amplitude, peak velocity or skewness, and no effect when the transducer was aimed at premotor cortex or in sham (transducer moved away) sessions.
Adverse eventsnone observedAll acoustic parameters (MI, ISPPA, ISPTA) were far below FDA diagnostic ultrasound imaging safety limits, and no discomfort was imposed on the animals during ultrasonic neurostimulation.

Exposures

Exposure 1: FUS to the left frontal eye field during antisaccade task

Target: frontal eye field — “left frontal eye field (FEF)
Device: Sonic Concepts · Sonic Concepts · H115

Pulse timing
Waveformcontinuous
Fundamental frequency (kHz)320✓✓
Pulse duration (ms)not applicable
Pulse repetition frequency (Hz)not applicable
Duty cycle (%)not applicable
Sonication duration (s)0.1✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)600✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatederatingmean or range across subjects
In-situ pressure (kPa)350✓✓
In-situ Isppa (W/cm²)4✓✓
In-situ Ispta (W/cm²)0.0135✓✓
Protocol, in the paper’s words

FUS pulses were delivered to the left FEF at a 100 ms stimulus onset asynchrony after visual target appearance, with rise and fall times of 1 ms, and a minimum 30 s pause between each ultrasonic pulse. Each session comprised a 100-trial AS baseline block, a 400-trial block (360 without FUS, 40 with FUS pseudorandomly interleaved, 20 per side), and a 100-trial posttest block.

Flags from extraction

  • exposures[0].in_situ.pressure_kpaThe 0.35 MPa in-brain value, ISPPA and ISPTA are derated estimates based on skull-transmission measurements at seven locations on an ex vivo macaque skull specimen (mean ± SD), not measurements in the live animals; reported_as coded as mean_or_range_across_subjects for lack of a closer category.
  • exposures[0].in_situ.ispta_w_cm2Paper reports ISPTA as an upper bound ('at less than 13.5 ± 3.8 mW/cm2'); the stated value is recorded as-is rather than as a strict mean.
  • sham_typeTwo distinct control manipulations were used: stimulation of a control site (premotor cortex) and a sham condition where the transducer was moved 4 cm away; both are listed.