Controlled noninvasive modulation of deep brain regions in humans
Thomas Riis, Daniel Feldman, Brian Mickey, Jan Kubanek
Communications Engineering 2024, 3 · 10.1038/s44172-023-00146-4
Abstract
Transcranial focused ultrasound provides noninvasive and reversible approaches for precise and personalized manipulations of brain circuits, with the potential to transform our understanding of brain function and treatments of brain dysfunction. However, effective applications in humans have been limited by the human head, which attenuates and distorts ultrasound severely and unpredictably. This has led to uncertain ultrasound intensities delivered into the brain. Here, we address this lingering barrier using a direct measurement approach that can be repeatedly applied to the human brain. The approach uses an ultrasonic scan of the head to measure and compensate for the attenuation of the ultrasound by all obstacles within the ultrasound path. No other imaging modality is required and the method is parameter-free and personalized to each subject. The approach accurately restores operators’ intended intensities inside ex-vivo human skulls. Moreover, the approach is critical for effective modulation of deep brain regions in humans. When applied, the approach modulates fMRI Blood Oxygen Level Dependent (BOLD) activity in disease-relevant deep brain regions. This tool unlocks the potential of emerging approaches based on low-intensity ultrasound for controlled manipulations of neural circuits in humans.
Abstract via crossref.
Exposures
Exposure 1: RTT-corrected ultrasound to subgenual cingulate cortex in major depression patients
Target: subgenual anterior cingulate cortex — “subgenual cingulate cortex (SGC)”
Device: custom-built · two 126-element phased arrays (650 kHz), driven by a Vantage256 (Verasonics) system ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 0.25 | ✓✓✓ |
| Duty cycle (%) | 0.8pulse duration × PRF gives 0.75%, which disagrees with the stated value | ✓✓✓ |
| Sonication duration (s) | 60 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 1,000 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 31 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.23 | ✓✓✓⚑ |
The ultrasound was delivered into the target (subgenual cingulate cortex) in 30 ms pulses (650 kHz, 1.0 MPa peak pressure) every 4 s. The stimulation was administered in 1-minute ON blocks, followed by 1-minute OFF blocks of no ultrasound, for a total of up to 10 min.
Flags from extraction
exposures[0].in_situ.ispta_w_cm2— Main results text states the delivered time-averaged intensity was 360 mW/cm2 ('the time-averaged intensity of 360 mW cm-2 safely complied with the FDA 510(k) Track 3 level of 720 mW/cm-2'), while the Methods 'Stimulation parameters' section states ISPTA = 0.23 W/cm2 (230 mW/cm2) for the same SGC stimulation. The two stated values disagree; the Methods value was recorded.sham_type— Sham delivered the same stimulus parameters and energy but unfocused ('the same stimulus parameters and energy but was not focused'); no vocabulary term precisely matches this mechanism, coded as other.n_sessions_per_subject— Paper does not state whether the two patients received more than one stimulation session.randomised— No randomisation procedure is described for the two-patient application (single stimulation session plus a sham condition); not stated as randomised or not.exposures[0].device.family— Transducer arrays are custom-built (PMN-PT elements) driven by a commercial Verasonics Vantage256 system; classified as custom_or_research for the transducer itself.