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Multi-target focused ultrasound neuromodulation of a subcallosal cingulate mediated depression network: A case study using personalized functional mapping

Benjamin Davidson, Ryan M. Jones, Dallan McMahon, Kristiana Xhima, Leonardo Favi Bocca, Yuexi Huang, Soraly Blanco, Christopher B. Pople, Peter Giacobbe, Sean M. Nestor, Jennifer S. Rabin, Clement Hamani, Kamil Uludag, Maged Goubran, Kullervo Hynynen, Nir Lipsman

Brain Stimulation 2026 · 10.1016/j.brs.2026.103198

human patientdepressionfmriclinical scaleother mri
Specieshuman
Subjects1 participants
Sessions per subject2
Randomisedyes
Blindingdouble
Sham / controlunfocused or detuned
Auditory controlnot reported
Readout timingoffline
Anaesthesianot applicable
Readoutsfmri, clinical scale, other mri — Resting-state fMRI sliding-window ROI-to-ROI connectivity among SCC, vmPFC and rACC; seed-to-brain connectivity; regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) and fractional-ALFF (fALFF); mood, anxiety and quality-of-life scales; structural MRI for safety
Direction of effectinhibitoryActive sonication produced a larger acute reduction in between-target (SCC-vmPFC-rACC) functional connectivity than sham approximately 1 hour post-treatment (Δr=-0.21, p<0.001), with return toward baseline by 24 hours; no clinical improvement in mood, anxiety or quality-of-life was observed.
Adverse eventsnone observedNo adverse events occurred, including sustained or clinically-significant worsening mood or anxiety, hypomanic symptoms, or structural MRI changes. The participant could not distinguish active from sham.

Exposures

Exposure 1: LIFU to subcallosal cingulate cortex (SCC), bilateral

Target: subgenual anterior cingulate cortex — “subcallosal cingulate cortex (SCC)”
Device: custom-built · clinical-prototype transmit/receive sparse hemispherical phased array (4096 transmit elements at 258 kHz, 256 receive elements at 129 kHz) ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)258✓✓✓
Pulse duration (ms)50✓✓✓
Pulse repetition frequency (Hz)0.45, 0.5swept✓✓✓⚑
Duty cycle (%)not reported
Sonication duration (s)400✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatesimulationsingle value
In-situ pressure (kPa)500✓✓✓⚑
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Six treatment volumes were selected: bilateral SCC, vmPFC, and rostral anterior cingulate cortex (rACC), sonicated sequentially within a single session. Active and defocused sham sonications were performed 4 weeks apart under maintained blinding; only LIFU operators knew allocation.

Exposure 2: LIFU to ventromedial prefrontal cortex (vmPFC), bilateral

Target: ventromedial prefrontal cortex — “ventromedial prefrontal cortex (vmPFC)”
Device: custom-built · clinical-prototype transmit/receive sparse hemispherical phased array (4096 transmit elements at 258 kHz, 256 receive elements at 129 kHz) ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)258✓✓✓
Pulse duration (ms)50✓✓✓
Pulse repetition frequency (Hz)0.45, 0.5swept✓✓✓
Duty cycle (%)not reported
Sonication duration (s)400✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatesimulationsingle value
In-situ pressure (kPa)500✓✓✓
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Six treatment volumes were selected: bilateral SCC, vmPFC, and rostral anterior cingulate cortex (rACC), sonicated sequentially within a single session. Active and defocused sham sonications were performed 4 weeks apart under maintained blinding; only LIFU operators knew allocation.

Exposure 3: LIFU to rostral anterior cingulate cortex (rACC), bilateral

Target: pregenual anterior cingulate cortex — “rostral anterior cingulate cortex (rACC)”
Device: custom-built · clinical-prototype transmit/receive sparse hemispherical phased array (4096 transmit elements at 258 kHz, 256 receive elements at 129 kHz) ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)258✓✓✓
Pulse duration (ms)50✓✓✓
Pulse repetition frequency (Hz)0.45, 0.5swept✓✓✓
Duty cycle (%)not reported
Sonication duration (s)400✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatesimulationsingle value
In-situ pressure (kPa)500✓✓✓
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Six treatment volumes were selected: bilateral SCC, vmPFC, and rostral anterior cingulate cortex (rACC), sonicated sequentially within a single session. Active and defocused sham sonications were performed 4 weeks apart under maintained blinding; only LIFU operators knew allocation.

Flags from extraction

  • exposures[0].in_situ.pressure_kpa — The 0.5 MPa value is described as a 'target-wise mean' CT-simulation-estimated in-situ pressure across the treated volumes, not a separate value per target; applied identically to all three target exposures (SCC, vmPFC, rACC) because the paper does not break the pressure down by individual target.
  • exposures[0].timing.pulse_repetition_frequency_hz — PRF is stated as a range (0.45-0.50 Hz), recorded as a two-element list per the range convention.
  • n_subjects — This is a single-subject case study (n=1 patient).
  • blinding — Text states 'only LIFU operators knew allocation', implying both participant and other assessors were blinded; classified as double-blind.