Neuromodulation with single‐element transcranial focused ultrasound in human thalamus
Wynn Legon, Leo Ai, Priya Bansal, Jerel K. Mueller
Human Brain Mapping 2018, 39, 1995-2006 · 10.1002/hbm.23981
Abstract
Transcranial focused ultrasound (tFUS) has proven capable of stimulating cortical tissue in humans. tFUS confers high spatial resolutions with deep focal lengths and as such, has the potential to noninvasively modulate neural targets deep to the cortex in humans. We test the ability of single-element tFUS to noninvasively modulate unilateral thalamus in humans. Participants (N = 40) underwent either tFUS or sham neuromodulation targeted at the unilateral sensory thalamus that contains the ventro-posterior lateral (VPL) nucleus of thalamus. Somatosensory evoked potentials (SEPs) were recorded from scalp electrodes contralateral to median nerve stimulation. Activity of the unilateral sensory thalamus was indexed by the P14 SEP generated in the VPL nucleus and cortical somatosensory activity by subsequent inflexions of the SEP and through time/frequency analysis. Participants also under went tactile behavioral assessment during either the tFUS or sham condition in a separate experiment. A detailed acoustic model using computed tomography (CT) and magnetic resonance imaging (MRI) is also presented to assess the effect of individual skull morphology for single-element deep brain neuromodulation in humans. tFUS targeted at unilateral sensory thalamus inhibited the amplitude of the P14 SEP as compared to sham. There is evidence of translation of this effect to time windows of the EEG commensurate with SI and SII activities. These results were accompanied by alpha and beta power attenuation as well as time-locked gamma power inhibition. Furthermore, participants performed significantly worse than chance on a discrimination task during tFUS stimulation.
Abstract via europepmc.
Exposures
Exposure 1: Unilateral sensory thalamus (VPL nucleus), EEG and behavioural experiments
Target: ventral posterolateral nucleus — “unilateral sensory thalamus that contains the ventro-posterior lateral (VPL) nucleus of thalamus”
Device: Ultran · Ultran Group, Inc., State College, PA ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.36 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 36pulse duration × PRF gives 36% | ✓✓✓ |
| Sonication duration (s) | 0.5 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 14.56 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 137.8 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 7.03 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
Channel 1 was used to gate channel 2 that was a 500 kHz sine wave. Channel 1 was a 5Vp-p square wave burst of 1 kHz (N=500) with a pulse width of 360 ms (as printed; see flag); this resulted in a 0.5 s duration waveform with a duty cycle of 36%. A total of 300 ultrasonic waveforms were delivered at an inter-stimulus interval (ISI) of 4 s for the EEG experiment; for the behavioural experiment, tFUS onset (500 ms duration) occurred 100 ms before pin application to the fingertip.
Consistency checks: intensity pressure inconsistent in situ.
Flags from extraction
exposures[0].timing.pulse_duration_ms— Text states a pulse width of '360 ms', but this is inconsistent with the stated 1 kHz PRF and 36% duty cycle, which imply a pulse duration of 0.36 ms (360 microseconds); recorded as printed per the burst-duration rule.exposures[0].in_situ— Paper also reports an intracranial peak pressure of 137.79 kPa obtained from a separate k-Wave simulation (a different method, on a generic Visible Human skull) using the same transducer/waveform; only the empirically measured through-skull intensity (method=measurement) is recorded here because the schema allows only one method per in_situ block.auditory_control— The paper does not use a standard auditory-control vocabulary term; it describes the sham (attenuating disk) as producing an audible sensation identical to the active condition, which is recorded here as 'other'.