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Remote, brain region–specific control of choice behavior with ultrasonic waves

Jan Kubanek, Julian Brown, Patrick Ye, Kim Butts Pauly, Tirin Moore, William Newsome

Science Advances 2020, 6 · 10.1126/sciadv.aaz4193

nonhuman primatehealthybehaviour

Abstract

The ability to modulate neural activity in specific brain circuits remotely and systematically could revolutionize studies of brain function and treatments of brain disorders. Sound waves of high frequencies (ultrasound) have shown promise in this respect, combining the ability to modulate neuronal activity with sharp spatial focus. Here, we show that the approach can have potent effects on choice behavior. Brief, low-intensity ultrasound pulses delivered noninvasively into specific brain regions of macaque monkeys influenced their decisions regarding which target to choose. The effects were substantial, leading to around a 2:1 bias in choices compared to the default balanced proportion. The effect presence and polarity was controlled by the specific target region. These results represent a critical step towards the ability to influence choice behavior noninvasively, enabling systematic investigations and treatments of brain circuits underlying disorders of choice.

Abstract via europepmc.

Speciesrhesus macaque (Macaca mulatta)
Subjects2 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlactive control site
Auditory controlnot reported
Readout timingonline
Anaesthesiaawake
Readoutsbehaviourtwo-alternative saccadic choice task with psychometric (sigmoid) curve fitting
Direction of effectexcitatoryStimulation of left/right FEF biased choices toward the contralateral target (~2:1, up to ~4:1 for initial trials in a block), interpreted as a positive (excitatory) bias of the decision process represented by neurons in the stimulated region; stimulation of a control site (motor cortex) produced no significant choice bias.
Adverse eventsnone observedNo adverse short- or long-term effects were observed.

Exposures

Exposure 1: FEF stimulation (left or right frontal eye fields)

Target: frontal eye field — “frontal eye fields (FEF)
Device: Sonic Concepts · Sonic Concepts · H-115

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)270✓✓
Pulse duration (ms)1✓✓
Pulse repetition frequency (Hz)500✓✓
Duty cycle (%)50pulse duration × PRF gives 50%✓✓
Sonication duration (s)0.3✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)600✓✓
Free-field Isppa (W/cm²)11.6✓✓
Free-field Ispta (W/cm²)0.581✓✓
In-situ estimatederating
In-situ pressure (kPa)320, 460swept✓✓
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Ultrasound was applied in blocks of three to six trials, strictly interleaved with blocks of three to six trials without stimulation. The stimulus was applied for 300 ms starting 100 ms before the onset of the first target, to modulate neurons throughout the decision-making process.

Exposure 2: Motor cortex control stimulation (left or right, 10 mm posterior to FEF)

Target: motor cortex — “motor cortex
Device: Sonic Concepts · Sonic Concepts · H-115

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)270✓✓
Pulse duration (ms)1✓✓
Pulse repetition frequency (Hz)500✓✓
Duty cycle (%)50pulse duration × PRF gives 50%✓✓
Sonication duration (s)0.3✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)600✓✓
Free-field Isppa (W/cm²)11.6✓✓
Free-field Ispta (W/cm²)0.581✓✓
In-situ estimatederating
In-situ pressure (kPa)320, 460swept✓✓
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

To control for indirect auditory/attentional confounds, the same stimuli were applied to a control region 10 mm more posterior to FEF (motor cortex); besides the change in stimulation location, data were collected in the same way as with FEF stimulation.

Flags from extraction

  • n_sessions_per_subjectSessions are reported per exposure/hemisphere (e.g., 8 per monkey for left FEF, 8 for right FEF, 11 sessions of left and 11 of right motor cortex pooled across animals); the paper does not state a single combined sessions-per-subject figure.
  • exposures[0].in_situ.pressure_kpaThis range is the authors' own estimate obtained by applying skull-attenuation percentages from two other papers (24% and 46/23%) to their free-field pressure, not a derating/simulation/measurement performed on the animals in this study; reported_as could not be classified into the given vocabulary and was left not_reported.
  • exposures[1].in_situ.pressure_kpaSame as exposures[0]: derived from literature attenuation estimates, not a study-specific derating.
  • readout_timingUltrasound was delivered 100 ms before target onset for a 300 ms duration, overlapping the early part of the choice/saccade process; the paper does not explicitly label the behavioral readout as online vs offline.
  • auditory_controlThe paper discusses the auditory-confound concern and addresses it via an active-control-site (motor cortex) design rather than a specific auditory-masking method, so no auditory_control vocabulary term applies.