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Transcranial Focused Ultrasound Modulates Intrinsic and Evoked EEG Dynamics

Jerel Mueller, Wynn Legon, Alexander Opitz, Tomokazu F. Sato, William J. Tyler

Brain Stimulation 2014, 7, 900-908 · 10.1016/j.brs.2014.08.008

human healthyhealthyeeg meg

Abstract

Background The integration of EEG recordings and transcranial neuromodulation has provided a useful construct for noninvasively investigating the modification of human brain circuit activity. Recent evidence has demonstrated that focused ultrasound can be targeted through the human skull to affect the amplitude of somatosensory evoked potentials and its associated spectral content. Objective/hypothesis The present study tests whether focused ultrasound transmitted through the human skull and targeted to somatosensory cortex can affect the phase and phase rate of cortical oscillatory dynamics. Methods A computational model was developed to gain insight regarding the insertion behavior of ultrasound induced pressure waves in the human head. The instantaneous phase and phase rate of EEG recordings before, during, and after transmission of transcranial focused ultrasound (tFUS) to human somatosensory cortex were examined to explore its effects on phase dynamics. Results Computational modeling results show the skull effectively reinforces the focusing of tFUS due to curvature of material interfaces. Neurophysiological recordings show that tFUS alters the phase distribution of intrinsic brain activity for beta frequencies, but not gamma. This modulation was accompanied by a change in phase rate of both beta and gamma frequencies. Additionally, tFUS modulated phase distributions in the beta band of early sensory-evoked activity but did not affect late sensory-evoked activity, lending support to the spatial specificity of tFUS for neuromodulation. This spatial specificity was confirmed through an additional experiment where the ultrasound transducer was moved 1 cm laterally from the original cortical target. Conclusions Focused ultrasonic energy can alter EEG oscillatory dynamics through local mechanical perturbation of discrete cortical circuits.

Abstract via europepmc.

Specieshuman
Subjects18, 7swept participants
Sessions per subject1
Randomisednot reported
Blindingsingle
Sham / controlinactive transducer, active control site
Auditory controlmasking sound
Readout timingonline
Anaesthesianot applicable
Readoutseeg megInstantaneous EEG phase and phase rate (beta 13-30 Hz, gamma 30-55 Hz) and spectral power at intrinsic and median-nerve somatosensory-evoked-potential (SEP) epochs
Direction of effectmixed or uncleartFUS altered the phase distribution of intrinsic beta (not gamma) EEG activity and the phase rate of both beta and gamma bands; evoked SEP phase effects were seen in the early but not late epoch. These are changes in oscillatory phase dynamics rather than a clear excitatory/inhibitory shift, and effects were abolished when the transducer was moved 1 cm laterally.
Adverse eventsnot reportedWe have previously verified this waveform does not produce heating of the skin or skull bone.

Exposures

Exposure 1: tFUS to somatosensory cortex (EEG site CP3)

Target: primary somatosensory cortex — “somatosensory cortex, targeted from 10-20 EEG site CP3 (effectively targeting S1)
Device: Blatek · Blatek, Inc.

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

A total of 120 ultrasonic stimuli (0.5 s each) were delivered at an ISI of 6 s (with 4 s positive randomisation) from EEG site CP3, with median nerve stimulation time-locked to occur 100 ms after tFUS onset (120 median nerve stimuli per condition). Sham and tFUS were run in a single session, counterbalanced across subjects; a separate cohort received tFUS 1 cm lateral to CP3 as a spatial-specificity control.

Flags from extraction

  • exposures[0].timing.pulse_duration_msEarlier in the same paragraph the methods state the pulse duration 'was set to 0.36 ms' (180 cycles at 0.5 MHz), but the summary waveform line states 'PD 360 ms'; 360 ms is inconsistent with the stated PRF (1 kHz) and stimulus duration (500 pulses in 0.5 s), so 0.36 ms is almost certainly correct and 360 ms a units typo. Recorded as stated in the summary specification line (360 ms) per the no-correction rule.
  • n_subjectsPaper gives two separate cohort sizes (18 at CP3, 7 at the 1-cm-lateral site) and never states a combined total.