Offline impact of transcranial focused ultrasound on cortical activation in primates
Lennart Verhagen, Cécile Gallea, Davide Folloni, Charlotte Constans, Daria EA Jensen, Harry Ahnine, Léa Roumazeilles, Mathieu Santin, Bashir Ahmed, Stéphane Lehericy, Miriam C Klein-Flügge, Kristine Krug, Rogier B Mars, Matthew FS Rushworth, Pierre Pouget, Jean-François Aubry, Jerome Sallet
eLife 2019, 8 · 10.7554/elife.40541
Abstract
To understand brain circuits it is necessary both to record and manipulate their activity. Transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation technique. To date, investigations report short-lived neuromodulatory effects, but to deliver on its full potential for research and therapy, ultrasound protocols are required that induce longer-lasting 'offline' changes. Here, we present a TUS protocol that modulates brain activation in macaques for more than one hour after 40 s of stimulation, while circumventing auditory confounds. Normally activity in brain areas reflects activity in interconnected regions but TUS caused stimulated areas to interact more selectively with the rest of the brain. In a within-subject design, we observe regionally specific TUS effects for two medial frontal brain regions - supplementary motor area and frontal polar cortex. Independently of these site-specific effects, TUS also induced signal changes in the meningeal compartment. TUS effects were temporary and not associated with microstructural changes.
Abstract via europepmc.
Exposures
Exposure 1: SMA TUS
Target: supplementary motor area — “SMA”
Device: Sonic Concepts · Sonic Concept, Bothell, WA, USA · H115-MR ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓⚑ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 30% | ⚑ |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | 1,170, 1,350swept | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 880 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 24.1 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 7.2 | ✓✓✓ |
30 ms bursts of 250 kHz ultrasound generated every 100 ms for 40 s, a single train over the midline targeting both hemispheres; fMRI began after the train ended.
Exposure 2: FPC TUS
Target: anterior prefrontal cortex — “FPC”
Device: Sonic Concepts · Sonic Concept, Bothell, WA, USA · H115-MR ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 30% | |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | 1,170, 1,350swept | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 1,010 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 31.7 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 9.5 | ✓✓✓ |
30 ms bursts of 250 kHz ultrasound generated every 100 ms for 40 s, a single train over the midline targeting both hemispheres; fMRI began after the train ended.
Flags from extraction
n_subjects— Six macaques received TUS in experiments 1-3 (3 in SMA/FPC within-subject, 3 in FPC replication); three further animals received pre-SMA TUS for histology (experiment 4) and are not counted.exposures[0].timing.duty_cycle_pct— Duty cycle not stated; 30 ms every 100 ms is given as bursts and interval.exposures[0].timing.pulse_repetition_frequency_hz— PRF of 10 Hz stated in the discussion; methods give a burst every 100 ms.auditory_control— Paper chose 250 kHz carrier and 10 Hz modulation to stay outside macaque hearing range and checked A1 coupling; no sound-masking or sham sound.exposures[0].free_field.pressure_kpa— Range 1.17-1.35 MPa across sessions as measured in water; also 1.2 MPa at 130 V in simulation section.exposures[0].in_situ.pressure_kpa— Simulated using a macaque CT; single transducer train over midline targets both hemispheres.sham_type— Control state had all procedures except TUS; other-site TUS also served as a control.
Notes: Experiment 4 stimulated pre-SMA (coordinates given) for histology in three further animals; it is not listed as a separate exposure.