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Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans

Wynn Legon, Tomokazu F Sato, Alexander Opitz, Jerel Mueller, Aaron Barbour, Amanda Williams, William J Tyler

Nature Neuroscience 2014, 17, 322-329 · 10.1038/nn.3620

human healthyhealthyeeg megbehaviour

Abstract

Improved methods of noninvasively modulating human brain function are needed. Here we probed the influence of transcranial focused ultrasound (tFUS) targeted to the human primary somatosensory cortex (S1) on sensory-evoked brain activity and sensory discrimination abilities. The lateral and axial spatial resolution of the tFUS beam implemented were 4.9 mm and 18 mm, respectively. Electroencephalographic recordings showed that tFUS significantly attenuated the amplitudes of somatosensory evoked potentials elicited by median nerve stimulation. We also found that tFUS significantly modulated the spectral content of sensory-evoked brain oscillations. The changes produced by tFUS on sensory-evoked brain activity were abolished when the acoustic beam was focused 1 cm anterior or posterior to S1. Behavioral investigations showed that tFUS targeted to S1 enhanced performance on sensory discrimination tasks without affecting task attention or response bias. We conclude that tFUS can be used to focally modulate human cortical function.

Abstract via europepmc.

Specieshuman
Subjects10, 8, 12, 12swept participants
Sessions per subjectnot reported
Randomisedyes
Blindingsingle
Sham / controlinactive transducer
Auditory controlsound only sham
Readout timingonline
Anaesthesianot applicable
Readoutseeg meg, behaviourSomatosensory evoked potential (SEP) peak-to-peak amplitudes and spectral power (alpha/beta/gamma bands) from median-nerve-evoked EEG; two-point and frequency (vibrotactile) discrimination thresholds (d') and response bias (criterion c)
Direction of effectinhibitorytFUS to S1 significantly reduced the amplitude of short-latency and late-onset somatosensory evoked potentials and decreased alpha/beta/gamma spectral power relative to sham, consistent with increased local inhibition; paradoxically, tFUS also improved two-point and frequency sensory discrimination performance without affecting attention or response bias. Effects were abolished when the beam was moved 1 cm anterior or posterior to S1.
Adverse eventsnone observedThe Isppa used (23.87 W/cm2) was below the 190 W/cm2 maximum recommended limit for diagnostic ultrasound imaging; volunteers reported no thermal or mechanical sensations from tFUS transmission through the scalp, and no perceptual differences between sham and tFUS were reported.

Exposures

Exposure 1: Primary somatosensory cortex (S1), main tFUS-vs-sham experiments (EEG and behavioural)

Target: primary somatosensory cortex — “crown of the postcentral gyrus and posterior wall of the central sulcus (S1), targeted via EEG electrode site CP3
Device: Blatek · Blatek, Inc., State College, PA

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)0.36✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 36%
Sonication duration (s)0.5✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)800✓✓
Free-field Isppa (W/cm²)23.87✓✓
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Each tFUS stimulus was a 500 ms train of 360 microsecond pulses at a 1 kHz pulse-repetition frequency (500 pulses total), delivered at an inter-stimulus interval of 6 s with 4 s positive randomisation; median nerve stimulation (for the EEG experiments) or the tactile/air-puff stimulus (for the behavioural experiments) began 100 ms after tFUS onset.

Exposure 2: 1 cm anterior control site (precentral gyrus), spatial-specificity experiment

Target: primary motor cortex — “brain region 1 cm anterior to CP3, in the precentral gyrus
Device: Blatek · Blatek, Inc., State College, PA

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)0.36✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 36%
Sonication duration (s)0.5✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)800✓✓
Free-field Isppa (W/cm²)23.87✓✓
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Each tFUS stimulus was a 500 ms train of 360 microsecond pulses at a 1 kHz pulse-repetition frequency (500 pulses total), delivered at an inter-stimulus interval of 6 s with 4 s positive randomisation; median nerve stimulation (for the EEG experiments) or the tactile/air-puff stimulus (for the behavioural experiments) began 100 ms after tFUS onset.

Exposure 3: 1 cm posterior control site, spatial-specificity experiment

Target: other — “brain region 1 cm posterior to CP3, posterior to the crown of the postcentral gyrus
Device: Blatek · Blatek, Inc., State College, PA

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)0.36✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 36%
Sonication duration (s)0.5✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)800✓✓
Free-field Isppa (W/cm²)23.87✓✓
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Each tFUS stimulus was a 500 ms train of 360 microsecond pulses at a 1 kHz pulse-repetition frequency (500 pulses total), delivered at an inter-stimulus interval of 6 s with 4 s positive randomisation; median nerve stimulation (for the EEG experiments) or the tactile/air-puff stimulus (for the behavioural experiments) began 100 ms after tFUS onset.

Flags from extraction

  • n_subjectsStudy comprises four partially-overlapping participant cohorts (SEP n=10, spatial-specificity n=8, two-point discrimination n=12, frequency discrimination n=12, with 10 of the frequency-discrimination subjects also completing two-point discrimination); the paper gives no single combined total, so all four group sizes are listed rather than summed.
  • exposures[0].in_situ.isppa_w_cm2The paper reports a general skull insertion loss (~fourfold drop in Isppa, -6.07 dB) measured across a range of free-space power levels during transducer characterisation, but never restates a specific post-skull (in-situ) pressure/intensity for the actual 23.87 W/cm2 / 0.80 MPa waveform used in the human experiments, so in_situ values are left not_reported rather than derated by the reviewer.
  • exposures[0].timing.duty_cycle_pctDuty cycle is not stated numerically anywhere in the paper for this waveform (only pulse duration 0.36 ms and PRF 1 kHz, from which it would be computable as ~36%), so it is left not_reported per the no-arithmetic rule.
  • exposures[2].target.termsThe posterior control site is described only as 'brain regions posterior to the crown of the postcentral gyrus', which does not map clearly onto a single named target in the vocabulary; classified as 'other'.