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Transcranial focused ultrasound stimulation of human primary visual cortex

Wonhye Lee, Hyun-Chul Kim, Yujin Jung, Yong An Chung, In-Uk Song, Jong-Hwan Lee, Seung-Schik Yoo

Scientific Reports 2016, 6 · 10.1038/srep34026

human healthyhealthyfmrieeg megbehaviour

Abstract

Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.

Abstract via europepmc.

Specieshuman
Subjects19 participants
Sessions per subject1, 2swept
Randomisedyes
Blindingdouble
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingonline
Anaesthesianot applicable
Readoutsfmri, eeg meg, behaviourself-reported phosphene perception (verbal description); BOLD fMRI activation mapping; sonication-triggered visual evoked EEG potentials (N55, P100)
Direction of effectexcitatoryFUS to V1 elicited phosphene perception in 11/19 (fully responsive) and 2/19 (partially responsive) subjects during fMRI, and in all 10 subjects during EEG sessions, together with V1 BOLD activation and network-wide fMRI activation (LGN, precuneus, fusiform, ITG, fronto-parietal, cingulate, thalamic and cerebellar regions) and evoked EEG peaks (N55, P100); sham FUS elicited no activation or sensation, indicating an excitatory/activating effect of sonication.
Adverse eventsnone observedNeurological examinations (blinded) before/after sonication, follow-up MRI at up to 4 weeks, and follow-up interviews at 2 months revealed no abnormal findings attributable to FUS; one subject reported a transient headache during the sham FUS fMRI condition that resolved quickly. Maximum estimated in-situ Isppa was 11.6 W/cm2 (MI 1.2, below the FDA imaging limit of 1.9); mean in-situ Ispta (~1.5 W/cm2) was below the IEC 60601 therapeutic-equipment limit of 3 W/cm2. Authors caution against very high sonication repetition rates (>500 times, every second) based on prior ovine microhemorrhage findings.

Exposures

Exposure 1: Transcranial FUS to primary visual cortex (V1), image-guided

Target: primary visual cortex — “primary visual cortex (V1)
Device: custom-built · MR-compatible single-element FUS transducer (focal length 3 cm; focus 3 mm diameter x 17 mm length, FWHM)

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)1,480✓✓
Free-field Isppa (W/cm²)16.6✓✓
Free-field Ispta (W/cm²)not reported
In-situ estimatesimulationmean or range across subjects
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)3?
In-situ Ispta (W/cm²)1.5✓✓
Protocol, in the paper’s words

Event-related fMRI was conducted during three conditions (FUS, sham FUS, photic stimulation); the 300-ms long stimulation was given 50 times every 13 s, synchronized with the MR scanner. In a separate EEG session outside the MRI (a subset of 10 participants), stimulation (FUS, sham FUS, or photic) was given 50 times every 2.5 s, with resting-state and sham FUS as additional conditions; condition order was randomized and balanced across participants.

Consistency checks: intensity pressure inconsistent free field.

Flags from extraction

  • n_sessions_per_subjectAll 19 participants had one FUS-fMRI session; a subset of 10 participants additionally underwent a separate FUS-EEG session, so sessions per subject were either 1 or 2 depending on participation in the EEG arm.
  • randomisedRandomisation described ('these conditions were randomized and balanced across the participants') refers to within-subject ordering of FUS/sham/photic conditions, not allocation to separate treatment groups.
  • exposures[0].in_situ.isppa_w_cm2Reported as a mean +/- SD across 19 subjects (0.7-6.6 W/cm2 range, mean 3.0+/-1.7); the mean is recorded per schema convention and the quote carries the full spread.