A Low-Intensity Transcranial Focused Ultrasound Parameter Exploration Study of the Ventral Capsule/Ventral Striatum
Tina Chou, Brian J. Kochanowski, Ashley Hayden, Benjamin M. Borron, Miguel C. Barbeiro, Junqian Xu, Joo-Won Kim, Xuefeng Zhang, Richard R. Bouchard, Kinh Luan Phan, Wayne K. Goodman, Darin D. Dougherty
Neuromodulation: Technology at the Neural Interface 2025, 28, 146-154 · 10.1016/j.neurom.2024.03.004
Abstract
Objectives Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective for treatment-resistant obsessive-compulsive disorder (OCD); however, DBS is associated with neurosurgical risks. Transcranial focused ultrasound (tFUS) is a newer form of noninvasive (ie, nonsurgical) stimulation that can modulate deeper regions, such as the VC/VS. tFUS parameters have just begun to be studied and have often not been compared in the same participants. We explored the effects of three VC/VS tFUS protocols and an entorhinal cortex (ErC) tFUS session on the VC/VS and cortico-striato-thalamo-cortical circuit (CSTC) in healthy individuals for later application to patients with OCD. Materials and methods Twelve individuals participated in a total of 48 sessions of tFUS in this exploratory multisite, within-subject parameter study. We collected resting-state, reward task, and arterial spin-labeled (ASL) magnetic resonance imaging scans before and after ErC tFUS and three VC/VS tFUS sessions with different pulse repetition frequencies (PRFs), pulse widths (PWs), and duty cycles (DCs). Results VC/VS protocol A (PRF = 10 Hz, PW = 5 ms, 5% DC) was associated with increased putamen activation during a reward task (p = 0.003), and increased VC/VS resting-state functional connectivity (rsFC) with the anterior cingulate cortex (p = 0.022) and orbitofrontal cortex (p = 0.004). VC/VS protocol C (PRF = 125 Hz, PW = 4 ms, 50% DC) was associated with decreased VC/VS rsFC with the putamen (p = 0.017), and increased VC/VS rsFC with the globus pallidus (p = 0.008). VC/VS protocol B (PRF = 125 Hz, PW = 0.4 ms, 5% DC) was not associated with changes in task-related CSTC activation or rsFC. None of the protocols affected CSTC ASL perfusion. Conclusions This study began to explore the multidimensional parameter space of an emerging form of noninvasive brain stimulation, tFUS. Our preliminary findings in a small sample suggest that VC/VS tFUS should continue to be investigated for future noninvasive treatment of OCD.
Abstract via europepmc.
Exposures
Exposure 1: Entorhinal cortex (ErC) tFUS
Target: entorhinal cortex — “entorhinal cortex (ErC)”
Device: BrainSonix · BrainSonix Corporation · BX Pulsar 1002 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 14.4 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.72 | ✓✓✓⚑ |
| Pressure, domain unspecified (kPa) | 680 | ✓✓✓ |
Sonication was delivered in 30-seconds-on/30-seconds-off blocks over a 20-minute session (10 minutes total active sonication) for the first (ErC) of four once-weekly tFUS sessions.
Exposure 2: VC/VS tFUS protocols A, B and C
Target: nucleus accumbens, internal capsule — “ventral capsule/ventral striatum (VC/VS)”
Device: BrainSonix · BrainSonix Corporation · BX Pulsar 1002 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 5, 0.4, 4swept | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 10, 125, 125swept | ✓✓✓ |
| Duty cycle (%) | 5, 5, 50swept | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 14.4 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.72 | ✓✓✓ |
| Pressure, domain unspecified (kPa) | 740, 740, 240swept | ✓✓✓ |
VC/VS was sonicated with an 80-mm focal length transducer in three within-subject protocols (A, B, C) delivered on separate once-weekly visits (protocols A and B order-counterbalanced across participants; protocol C always last), each using 30-seconds-on/30-seconds-off blocks over a 20-minute session (10 minutes active sonication).
Flags from extraction
randomised— ErC session was always first and protocol C always last (only A/B order was counterbalanced); authors explicitly note as a limitation that 'Future studies should randomize the order of different tFUS protocols', indicating the actual session order was not randomised.sham_type— No inert sham arm was used; the ErC session (different target, real ultrasound) served as the closest comparison condition, coded as active_control_site.exposures[0].in_situ.ispta_w_cm2— The text states a single derated ISPTA (0.72 W/cm2) and ISPPA (14.4 W/cm2) 'for all' four tFUS sessions despite protocols differing markedly in duty cycle (5% vs 50%) and stated pressure (0.24-0.74 MPa); applied identically to both exposures per the text, but the constancy across very different duty cycles is unusual and worth checking.exposures[1].timing.pulse_duration_ms— List order is [protocol A, protocol B, protocol C] = PW 5 ms, 0.4 ms, 4 ms; duty_cycle_pct and pressure lists follow the same order.