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Electrophysiological Source Imaging of Brain Networks Perturbed by Low-Intensity Transcranial Focused Ultrasound

Kai Yu, Abbas Sohrabpour, Bin He

IEEE Transactions on Biomedical Engineering 2016, 63, 1787-1794 · 10.1109/tbme.2016.2591924

rodenthealthyeeg meg

Abstract

Objective Transcranial focused ultrasound (tFUS) has been introduced as a noninvasive neuromodulation technique with good spatial selectivity. We report an experimental investigation to detect noninvasive electrophysiological response induced by low-intensity tFUS in an in vivo animal model and perform electrophysiological source imaging (ESI) of tFUS-induced brain activity from noninvasive scalp EEG recordings. Methods A single-element ultrasound transducer was used to generate low-intensity tFUS ( ) and induce brain activation at multiple selected sites in an in vivo rat model. Up to 16 scalp electrodes were used to record tFUS-induced EEG. Event-related potentials were analyzed in time, frequency, and spatial domains. Current source distributions were estimated by ESI to reconstruct spatiotemporal distributions of brain activation induced by tFUS. Results Neuronal activation was observed following low-intensity tFUS, as correlated to tFUS intensity and sonication duration. ESI revealed initial focal activation in cortical area corresponding to tFUS stimulation site and the activation propagating to surrounding areas over time. Conclusion The present results demonstrate the feasibility of noninvasively recording brain electrophysiological response in vivo following low-intensity tFUS stimulation, and the feasibility of imaging spatiotemporal distributions of brain activation as induced by tFUS in vivo. Significance The present approach may lead to a new means of imaging brain activity using tFUS perturbation and a closed-loop ESI-guided tFUS neuromodulation modality.

Abstract via europepmc.

Speciesrat (Wistar)
Subjects3 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer
Auditory controlsound only sham
Readout timingboth
Anaesthesiaanaesthetised
Readoutseeg megEvent-related potentials, mean global field power (MGFP), time-frequency (short-time Fourier transform) spectral analysis, EEG source imaging (minimum-norm electrophysiological source imaging)
Direction of effectexcitatoryLow-intensity tFUS (Ispta < 1 mW/cm2) evoked time-locked EEG activation whose amplitude/extent increased with sonication intensity and duration; source imaging showed initial activation at the targeted cortical site that propagated to surrounding regions during ongoing sonication.
Adverse eventsnot reportedApplied intensities (Ispta 0.1-0.6 mW/cm2, Isppa 0.74-4.6 mW/cm2) were far below FDA diagnostic ultrasound imaging limits (Ispta 720 mW/cm2, Isppa 190 W/cm2) and below the lowest Ispta previously reported to be neuromodulatory in vivo; no hindlimb EMG response was observed at these intensities.

Exposures

Exposure 1: Low-intensity tFUS of rat anterior cortex

Target: frontal lobe — “right/left anterior cortex
Device: Olympus / Panametrics · Olympus · V389

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)2,000✓✓
Duty cycle (%)not reported
Sonication duration (s)0.005, 0.05, 0.2swept✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatemeasurementmean or range across subjects
In-situ pressure (kPa)18.3, 27.9, 45.9swept✓✓
In-situ Isppa (W/cm²)0.0007, 0.0014, 0.0046swept✓✓
In-situ Ispta (W/cm²)0.0001, 0.0002, 0.0006swept✓✓
Protocol, in the paper’s words

tFUS pulses were produced in a burst mode by a single-element focused transducer using a single-pulse burst mode (rather than a tens-of-cycles tone-burst) at a 2 kHz pulse repetition frequency, delivered through a conical collimator to a scalp site, with 3 s intersonication intervals. Three sonication intensities (SI1-SI3) were tested at a fixed 200 ms sonication duration in one experiment; a second experiment compared 5, 50, and 200 ms sonication durations at a fixed intensity (Ispta 0.6 mW/cm2). A sham condition used the same 200 ms sonication with the transducer aimed away from the animal.

Flags from extraction

  • exposures[0].target.termsFigures describe the sonicated site only as 'right anterior cortex' / 'left anterior cortex'; no more specific named cortical subregion is given, so mapped to frontal_lobe as the closest match.
  • exposures[0].in_situ.methodIntensities/pressures were measured with a calibrated hydrophone placed behind a piece of freshly excised Wistar rat skull, i.e. measured through skull, matching the 'measurement' in_situ method.
  • exposures[0].timing.pulse_duration_msPaper contrasts its 'single-pulse burst mode' with the tone-burst mode (tens of cycles per pulse) used in prior studies, but never states the duration of an individual pulse in ms; only the pulse repetition frequency (2 kHz) of pulses within the sonication train is given, so pulse_duration_ms is left not_reported (burst-rule ambiguity).