Transcranial focused ultrasound stimulation of cortical and thalamic somatosensory areas in human
Hyun-Chul Kim, Wonhye Lee, Daniel S. Weisholtz, Seung-Schik Yoo
PLOS ONE 2023, 18, e0288654 · 10.1371/journal.pone.0288654
Abstract
The effects of transcranial focused ultrasound (FUS) stimulation of the primary somatosensory cortex and its thalamic projection (i.e., ventral posterolateral nucleus) on the generation of electroencephalographic (EEG) responses were evaluated in healthy human volunteers. Stimulation of the unilateral somatosensory circuits corresponding to the non-dominant hand generated EEG evoked potentials across all participants; however, not all perceived stimulation-mediated tactile sensations of the hand. These FUS-evoked EEG potentials (FEP) were observed from both brain hemispheres and shared similarities with somatosensory evoked potentials (SSEP) from median nerve stimulation. Use of a 0.5 ms pulse duration (PD) sonication given at 70% duty cycle, compared to the use of 1 and 2 ms PD, elicited more distinctive FEP peak features from the hemisphere ipsilateral to sonication. Although several participants reported hearing tones associated with FUS stimulation, the observed FEP were not likely to be confounded by the auditory sensation based on a separate measurement of auditory evoked potentials (AEP) to tonal stimulation (mimicking the same repetition frequency as the FUS stimulation). Off-line changes in resting-state functional connectivity (FC) associated with thalamic stimulation revealed that the FUS stimulation enhanced connectivity in a network of sensorimotor and sensory integration areas, which lasted for at least more than an hour. Clinical neurological evaluations, EEG, and neuroanatomical MRI did not reveal any adverse or unintended effects of sonication, attesting its safety. These results suggest that FUS stimulation may induce long-term neuroplasticity in humans, indicating its neurotherapeutic potential for various neurological and neuropsychiatric conditions.
Abstract via europepmc.
Exposures
Exposure 1: Primary somatosensory cortex (S1) stimulation
Target: primary somatosensory cortex — “primary somatosensory cortex (S1, non-dominant hand representation)”
Device: Ultran · Ultran Group · GPS200-D40-FL57 (D40) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 0.5, 1, 2swept | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,400, 700, 350swept | ✓✓✓ |
| Duty cycle (%) | 70 | ✓✓✓ |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 14.7 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 4.1 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 2.9 | ✓✓✓ |
Three pulse-duration (PD) conditions (0.5, 1, 2 ms), each 200 ms long, delivered at a constant 70% duty cycle (PRF adjusted per PD). Trials were administered 4 s apart; 80 trials per PD condition were given in randomized, balanced order together with a passive sham (no sonication) condition, for a session lasting ~21 min (1,280 s).
Exposure 2: Ventral posterolateral thalamic nucleus (VPL) stimulation
Target: ventral posterolateral nucleus — “ventral posterolateral nucleus (VPL), thalamic projection of the somatosensory circuit”
Device: Ultran · Ultran Group · GPS200-D90-FL130 (D90) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 0.5, 1, 2swept | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,400, 700, 350swept | ✓✓✓ |
| Duty cycle (%) | 70 | ✓✓✓ |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 9.1 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 3.4 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 2.4 | ✓✓✓ |
Same pulse scheme as the S1 session (three PD conditions of 0.5, 1, 2 ms, each 200 ms long, 70% duty cycle, PRF adjusted per PD), delivered via the D90 transducer about a week after the S1 session; 80 trials per PD condition plus sham, 4 s apart, ~21 min session.
Flags from extraction
auditory_control— No concurrent auditory masking was used during FUS sessions; instead, auditory evoked potentials to mimicking tones were measured in a separate group of participants after the fact to assess possible auditory confounds, which does not fit cleanly into the closed vocabulary.randomised— Session order (S1 always Visit #2, VPL always Visit #3) was fixed rather than randomized across participants; within-session trial order (PD conditions and sham) was randomized and balanced, but no explicit statement of subject/group-level randomisation is given.sham_type— The 'passive sham' consisted of the transducer remaining in place with no sonication triggered during that trial, interpreted as inactive_transducer.