Transcranial focused ultrasound targeting the default mode network for the treatment of depression
Jessica N. Schachtner, Jacob F. Dahill-Fuchel, Katja E. Allen, Christopher R. Bawiec, Peter J. Hollender, Sarah B. Ornellas, Soren D. Konecky, Achal S. Achrol, John J. B. Allen
Frontiers in Psychiatry 2025, 16 · 10.3389/fpsyt.2025.1451828
Abstract
Introduction Up to 50% of individuals fail to respond to current depression treatments. Repetitive negative thought and default mode network hyperconnectivity are central in depression and can potentially be targeted using novel neuromodulation techniques. This community-based study assessed whether a treatment using non-invasive transcranial focused ultrasound targeting the default mode network can decrease depression symptoms and repetitive negative thought, and improve quality of life. Methods Study recruitment began in August 2023 and ended in February 2024. Twenty individuals aged 18 - 50 were enrolled from among 247 screened. Exclusion criteria included history of psychosis/mania, acute suicidality, MRI contraindications, pregnancy, and medical and neurological factors that may complicate diagnosis or brain function. Participants completed up to three weeks of transcranial ultrasound (11 sessions) targeting the anterior medial prefrontal cortex; ten minutes per session. Depression severity (Beck Depression Inventory - II and the Hamilton Depression Rating Scale), repetitive negative thought (Perseverative Thinking Questionnaire), and quality of life (World Health Organization Quality of Life Scale) were outcomes. Results This sample was young (mean 30.4 years ± 10.0), predominantly female (75%), with moderate to severe depression and high comorbidity. Fifty percent of participants endorsed current psychiatric medication use. Ten percent of subjects dropped out of the study due to time constraints. Significant decreases in depression were observed over the course of treatment on self-report, 10.9 (p Discussion Non-invasive transcranial focused ultrasound holds promise as a treatment for depression holds promise as a treatment for depression, however, future work including control arms is required to ascertain its causal role in depression. Clinical trial registration https://clinicaltrials.gov/study/NCT06320028intr=Ultrasound&cond=depression&locStr=Arizona&country=United%20States&state=Arizona&rank=1, identifier NCT06320028.
Abstract via europepmc.
Exposures
Exposure 1: amPFC tFUS for depression
Target: anterior prefrontal cortex — “left anterior-medial prefrontal cortex (amPFC)”
Device: Openwater · Openwater · custom Neuromodulation device, 128-element ultrasound array ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 400 | ✓✓✓ |
| Pulse duration (ms) | 5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 5% | ⚑ |
| Sonication duration (s) | 600 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Pressure, domain unspecified (kPa) | 820 | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 0.67 | ✓✓✓ |
Participants completed up to three weeks of transcranial ultrasound (up to 11 sessions total: 5 sessions in week 1, then, for those not meeting early-remission criteria, 3 sessions per week for two more weeks), each session lasting ten minutes, targeting the left amPFC via electronically-steered beam-forming with a multi-foci radial pattern of five sub-foci.
Flags from extraction
n_sessions_per_subject— The protocol allowed early termination after 5 sessions (week 1) if remission criteria were met, so not all participants completed all 11 sessions; recorded 11 as the designed maximum stated in the abstract/methods.exposures[0].target.terms— The paper's own target name is 'anterior-medial prefrontal cortex (amPFC)'; mapped to 'anterior_prefrontal_cortex' (frontopolar/BA10, closest listed term given the anterior MNI y-coordinate of 45) rather than 'ventromedial_prefrontal_cortex', though the paper's wording ('medial prefrontal') could also support the latter; flagged for review.exposures[0].timing.duty_cycle_pct— Duty cycle is not explicitly stated as a percentage in the text (only pulse duration = 5 ms and PRR = 10 Hz are given); left not_reported rather than computed.exposures[0].unspecified_domain.pressure_kpa— Peak negative pressure (820 kPa) and spatial-peak/temporal-average intensity (670 mW/cm2) are given without stating whether they are free-field (water) or in-situ (skull-corrected) values; recorded as unspecified_domain.direction_of_effect— Functional connectivity/DMN modulation was not measured in this study; the inhibitory direction is the authors' hypothesis based on stimulation parameters, not a measured outcome.